Wissenschaftliche Aufbereitung zu ( Wirkstoff )

Transcription

Bewertung der Expertengruppe Off-Label im Bereich Onkologie
nach § 35c SGB V
zur Anwendung von
„Etoposid bei Sarkomen in Kombination mit Carboplatin“
1.a
29.06.2011
Wirkstoff (INN)
1.a.a Etoposid bzw. Etoposidphosphat
1.a.b Carboplatin
1.b
Im Geltungsbereich des AMG zugelassene Fertigarzneimittel
1.b.a Fertignarzneimittel mit dem Wirkstoff Etoposid bzw. Etoposidphosphat
(AMIS-Recherche aktualisiert am 31.01.2011; Suchbegriffe:“Etoposid?“ und „verkehrsfähig“)
Vepesid® J 100mg, 500mg, 1000mg
Vepesid® K 50mg,100mg
Etopophos® 100mg, 1000mg
Bristol-Myers-Squibb, Berlin
Vepesid®
Parallelimporte von Beragena Arzneimittel
GmbH, EMRA-Med Arzneimittel GmbH,
Kohlpharma GmbH
Etopofos 10mg
CC
Eto-Gry 20mg/ml
Teva
Pharma GbmH, Densborn
Deutschland, Kirchzarten
Etomedac® 20mg/ml
Medac GmbH, NL (Vertrieb: Hamburg)
Neoposid® 20mg/ml
NeoCorp
Riboposid® 20mg/ml
Etoposid Ribosepharm
Ribosepharm
Eto-cell 20mg/ml
Cell
Etoposid Hexal 50mg, 100mg,
200mg, 400mg, 1000mg
Etoposid Hexal sine 20mg/ml
Etoposid Sandoz 50mg, 100mg, 200mg,
400mg, 1000mg Hexal
Exitop®
AG, Weilheim
Baxter
Lastet 25mg, 50mg, 100mg Weichkapsel
Onkoposid®
Onkoworks
und
Spezialpräp
Etoposid Oncotrade 20mg/ml
GmbH, München
Pharm GmbH, Bad Vilbel
Hexal AG, Holzkirchen
Sandoz Pharmaceuticals Gmbh, Holzkirchen
Onkologie GmbH, Halle
Cancernova GmbH Reute
Gesellschaft für Herstellung
Vertrieb onkologischer
arate mbH, München
Oncotrade GmbH & Co. KG, Haan
Seite: 1
1.b.b
Im Geltungsbereich des AMG zugelassene Fertigarzneimittel
(AMIS-Recherche aktualisiert am 31.01.2011; Suchbegriffe:“Carboplatin?“ und „verkehrsfähig“)
Haemato-carb®
Haemato
Carbox®
Medicopharm
Carboplatin Accord®
Accord
Carboplatin Cancernova ®
Pharm AG, Brandenburg
AG, Nußdorf am Inn
Healthcare; GB
Canceronova GmbH, Grünwald
Carboplatin Hospira®
Hospira
Carbomedac®
medac
Carboplatin Gry®
Gry-Pharma
Neocarbo®
Neocorp
Axicarb®
axios
Deutschland GmbH, München
Gesellschaft, Hamburg
GmbH, Radebeul
AG, Weilheim
Pharma, Bielefeld
Carboplatin Sandoz®
Sandoz Pharmaceuticals GmbH,
Holzkirchen
Carboplatin onkovis®
Onkovis
Carboplatin Bendalis® und Carboplatin EBEWE
Carboplatin ratiopharm®
Ratiopharm,
Ribocarbo-L
HIKMA
Carbo Cell
cell
Carboplatin Hexal
GmbH, Penzberg
EBEWE Pharma, Unterach am Attersee
Ulm
Farmaceutica, Portugal
Pharm GmbH, Bad Vilbel
Hexal
AG, Holzkirchen
Eurocarboplatin
Lapharm GmbH, Rosenheim
Carboplatin ESP
ESP Pharma Ltd., GB
Carboplatin O.R.C.A.
AWD.pharma GmbH & Co. KG, Radebeul
Zytax®
Hikama
Farmaceuticals, Portugal
Seite: 2
2.
Im Geltungsbereich des AMG zugelassene Indikationen
2.a.a Etoposid
Etoposid ist in Kombinationmit anderen antineoplastischwirksamen Praparaten bei der
Behandlung folgender bosartiger Neubildungen angezeigt:
• Palliative Therapie des fortgeschrittenen, kleinzelligen Bronchialkarzinoms
• In einigen Fällen zur palliativen Therapie des fortgeschrittenen, nicht-kleinzelligen
Bronchialkarzinoms
• Reinduktionstherapie bei Morbus Hodgkin nach Versagen (nicht vollstandiges Ansprechen
auf die Therapie bzw. Wiederauftreten der Erkrankung) von Standardtherapien
• Non-Hodgkin-Lymphome von intermediarem und hohem Malignitatsgrad nach Versagen
(nicht vollstandiges Ansprechen auf die Therapie bzw. Wiederauftreten der Erkrankung) von
Standardtherapien.
In der Mono- und Polychemotherapie ist Etoposid angezeigt zur Behandlung der akuten
myeloischen Leukamie bei Patienten, für die eine intensive, myeloablative Therapie nicht
geeignet ist.
In der Monotherapie ist LASTET angezeigt • zur Behandlung des rezidivierten oder therapierefraktaren Hodenkarzinoms
• zur palliativen systemischen Behandlung fortgeschrittener Ovarialkarzinome nach
Versagen von platinhaltigen Standardtherapien.
(Fachinformation für Lastet® 25, 50, 100 mg Cancernova GmbH, Stand November 2010)
2.a.b Etoposidphosphat
Etoposidphosphat ist in Kombination mit anderen antineoplastisch wirksamen Arzneimitteln
bei der Behandlung folgender bösartiger Neubildungen angezeigt:
– Kleinzelliges Bronchialkarzinom;
– Palliative Therapie des fortgeschrittenen nicht-kleinzelligen Bronchialkarzinoms
bei Patienten in gutem Allgemeinzustand (Karnofsky-Index _80 %);
– Reinduktionstherapie bei Morbus Hodgkin nach Versagen von Standardtherapien
(nicht vollständiges Ansprechen auf bzw. Wiederauftreten nach Standardtherapien);
– Non-Hodgkin-Lymphome von intermediärem und hohem Malignitätsgrad;
– Remissionsinduktion bei akuter myeloischer Leukämie im Kindesalter;
– Reinduktionstherapie nach Versagen (nicht vollständiges Ansprechen bzw.Wiederauftreten der Erkrankung) von Standardtherapien bei akuter myeloischer Leukämie im
Erwachsenenalter;
– Hodentumoren;
– Chorionkarzinom der Frau mit mittlerem oder hohem Risiko nach dem Prognoseschema
der WHO.
In der Monotherapie ist Etoposidphosphat bei der palliativen systemischen Behandlung
fortgeschrittener Ovarialkarzinome nach Versagen von Platin-haltigen Standardtherapien
angezeigt.
(Fachinformation für Etopophos® 100 mg, Bristol-Myers Squibb, Stand August 2008)
2.b
Carboplatin
Carboplatin ist allein oder in Kombination mit anderen antineoplastisch wirksamen
Medikamenten bei der Behandlung folgender maligner Geschwülste angezeigt:
• epitheliale Ovarialkarzinome,
• kleinzellige Bronchialkarzinome,
• Karzinome des Kopf-Hals-Bereichs,
• Zervixkarzinome,
zur palliativen Therapie von Zervixkarzinomen bei Lokalrezidiven oder Fernmetastasierung,
(Fachinformation für Neocarb® 10mg/ml, NeoCorp AG, Stand März 2009)
.
Seite: 3
3. Epidemiologische Daten zur beurteilten Indikation
1% aller Malignome sind Weichteilsarkome. Die Inzidenz liegt bei 2-3 Neuerkrankungen
pro 100.000 Männer und Frauen, entsprechend ist mit 2000-3000 Neuerkrankungen pro
Jahr in Deutschland zu rechnen (Cerny et al. 2006). Der Altersgipfel bei Kindern liegt
zwischen 13-60 Monaten, bei Erwachsenen zwischen 45 und 55 Jahren.
Weichteilsarkome bei Kindern machen 6.2% der kindlichen Krebserkrankungen aus
(Robert-Koch-Institut 2008).
Weichteilsarkome stellen eine sehr vielfältige Gruppe maligner Tumoren dar. Sie
entstehen in den Weichteilen und bilden die viertgrößte Gruppe solider Tumoren im
Kindesalter (nach Hirntumoren, Lymphomen und Neuroblastomen). Der häufigste bei
Kindern auftretende Tumor aus der Gruppe der Weichteilsarkome ist das
Rhabdomyosarkom (Koscielniak und Klingebiel 2009, Robert Koch-Institut 2009).
Der Begriff Weichteilsarkome bezeichnet eine Gruppe von Tumoren, die sich nach der
WHO-Klassifikation aus 60 verschiedenen Subentitäten zusammensetzt und
histopathologisch und molekulargenetisch definiert sind. Bei Erwachsenen überwiegen
Liposarkome, Fibrosarkome, pleomorphe Sarkome und Leiomyosarkome, bei Kindern
und Jugendlichen Rhabdomyosarkome, extraossäre Ewing-Sarkome, periphere primitive
neuroektodermale Tumoren (pPNET), Synovialsarkome und Neurofibrosarkome.
Etwa 40% der Weichteilsarkome entstehen an der unteren Extremität, 30% am
Körperstamm und jeweils 15% an der oberen Extremität und im Kopf-Hals-Bereich
(Schütte et al. 2006).
Ursache und Entstehung der Weichteilsarkome sind bis heute weitgehend unbekannt.
Nur bei einem geringen Teil der Patienten lassen sich Prädispositionen finden wie das LiFraumeni-Syndrom oder die Neurofibromatose. Bei AIDS-Patienten und bei Patienten mit
einem klassischen Kaposi-Sarkom scheint ätiologisch ein neues Herpesvirus-8 eine Rolle
zu spielen (Cerny et al. 2006, Koscielniak et al. 2002).
Für die Prognose von Weichteilsarkomen, also vor allem für die Heilungsmöglichkeiten und
das Rezidivrisiko, sind folgende tumorbedingte und therapiebedingten Prognosefaktoren von
übergeordneter Bedeutung:
1. Größe des Primärtumors: größer oder kleiner als 5 cm in der größten Ausdehnung
(T-Klassifikation)
2. Histopathologisches Grading (G1-G3): Mitosehäufigkeit, Nekrosen
3. Ausmaß der chirurgisch tumorfreien Resektionsränder: R0, R1, R2
4. M-Klassifikation: Vorliegen von keinen oder von Fernmetastasen: M0, M1
5. Histopathologische Subentität
6. Lokalisation des Primärtumors
7. Nodaler Status: N-Klassifikation
8. Alter: über oder unter 10 Jahre
Seite: 4
In dem vorliegenden Gutachten werden nur Weichteilsarkome berücksichtigt, da über die
Behandlung der Patienten mit Ewing-Sarkomen bereits ein Gutachten vorliegt und die
Knochensarkome (Osteasarkome) der Kinder und Erwachsenen eine völlig andere
Tumorentität darstellt. Deshalb werden Patienten mit Knochensarkome chirurgisch,
strahlentherapeutisch und chemotherapeutisch in speziellen Protokollen behandelt
(Cooperative Osteosarkomstudiengruppe COSS. EURAMOS 1. Clinical trail protocol,
Version 1.3. Amended, 31.7.2007).
4.
Zugelassene Wirkstoffe für die beurteilte Indikation (Weichteil-Sarkome):
(AMIS-Recherche am 31.01.2011 Suchbegriffe „sarkom?“ and „rhabdomyo?“ not
„?ewing?“ not „?kaposi?“ and verkehrsfähig, positiv)
Ifosfamid
….. Weichteilsarkome (inkl. Osteosarkom und Rhabdomyosarkom)
Zur Einzel- oder Kombinationschemotherapie des Rhabdomyosarkoms oder des
Osteosarkoms nach Versagen der Standardtherapien.
Zur Einzel- oder Kombinationschemotherapie anderer Weichteilsarkome nach Versagen der
Chirurgie und Strahlentherapie……
(Fachinformation für Holoxan® Holoxan® Lösung 2g, Baxter Oncology GmbH, Stand November 2008)
Doxorubicin (Adriamycin)
…… Fortgeschrittenes Weichteilsarkom des Erwachsenenalters Ewing-Sarkom
Frühstadium des Hodgkin-Lymphoms…….
(Fachinformation für Adrimedac®, medac, Stand November 2007)
Epirubicin
Mammakarzinom, Fortgeschrittenes Ovarialkarzinom, Kleinzelliges Bronchialkarzinom,
Fortgeschrittenes Magenkarzinom, Fortgeschrittenes Weichteilsarkom, Intravesikale
Anwendung zur Rezidivprophylaxe (adjuvante Therapie) oberflächlicher Harnblasenkarzinome (Ta, T1) nach TUR
(Fachinformation für Farmorubicin® 50mg HL, Pharmacia GmbH, Stand Juli 2008)
Trabectedin
Trabectedin ist indiziert für die Behandlung von Patienten mit fortgeschrittenem
Weichteilsarkom nach Versagen von Anthrazyklinen und Ifosfamid, bzw. von Patienten, bei
denen sich die Anwendung dieser Mittel nicht eignet.
DieWirksamkeitsdaten basieren vorwiegend auf Patienten mit Liposarkom und
Leiomyosarkom……..
(Fachinforamtion für Yondelis® 1mg, Pharma Mar Spanien, Stand September 2007)
Tasonermin
Tasonermin wird bei nichtresezierbaren Weichteilsarkomen der Extremitäten in Kombination
mit Melphalan über eine isolierte Extremitäten-Perfusion (ILP – isolated limb perfusion) unter
milder Hyperthermie verabreicht
- zur Vorbereitung auf eine operative Entfernung des Tumors, umeineAmputation zu
vermeiden bzw. zu verzögern,
- oder zur palliativen Behandlung.
(Fachinforamtion für Beromun®, Boehringer Ingelheim International GmbH, Stand März 2009)
Seite: 5
Cyclophosphamid
… – Ewing-Sarkom…
… – Rhabdomyosarkom bei Kindern…
(Fachinforamtion für Endoxan®, Baxter Oncology GmbH, Stand November 2008)
Dactinomycin
Dieses Arzneimittel ist im Rahmen eines multimodalen Therapieregimes zur Primärtherapie
des Wilms-Tumor, des kindlichen Rhabdomyosarkoms und des lokalisierten Ewing-Sarkoms
angezeigt.
Dieses Arzneimittel ist indiziert als Monotherapie oder im Rahmen eines multimodalen
Therapieregimes bei Chorionkarzinom.
(keine Anzeige in FI-Service, zugelassene Anwendungsgebiete lt. AMIS für Lyovac-Cosmegen,
Lundbeck Irland, Stand 06.04.2005
Vincristin
…– Sarkome (osteogenes Sarkom, Ewing- Sarkom, Rhabdomyosarkom),……
(Fachinformation für Vincristinsulfat-Gry, GRY-Pharma GmbH, Stand November 2006)
5. Weitere Behandlungsstrategien/Outcome
5.1. Autologe Stammzelltransplantation.
Zur Bedeutung der autologen Stammzelltransplantation bei Weichteilsarkomen wurde 2009
ein umfangreiches Gutachten des Instituts für Qualität und Wirtschaftlichkeit im
Gesundheitswesen (IQWiG) veröffentlicht (IQWiG-Berichte-Jahr 2009 Nr. 63). Ausgewertet
wurden Daten von insgesamt 105 relevanten Studien mit 653 transplantierten Patienten mit
Weichteilsarkomen IQWiG-bericht Nr. 63, 2009). Der Bericht kommt zu dem Fazit, “dass
zum Zeitpunkt der Veröffentlichung die verfügbare Evidenz nicht ausreicht, um einen
möglichen Nutzen oder Schaden der autologen Stammzelltransplantation bei Patienten mit
Weichteilsarkomen zu belegen ist“ (Seite 85).
5.2. Hyperthermie
Die kürzlich von Issels et al. in Lancet Oncology 2010 publizierte Studie konnte erstmals in
einem randomisierten Vergleich zeigen, dass die lokale Hyperthermie in Kombination mit der
neoadjuvanten Chemotherapie mit Etoposid, Ifosfamid und Doxorubicin (Adriamycin) (EIA)
bei Patienten mit lokalisierten Hochrisiko-Weichteilsarkomen die Remissionsraten, das lokale
Progressions-freie Überleben sowie das krankheitsfreie Überleben signifikant verbessert.
5.3. Alleinige Chirurgie
Zum Zeitpunkt der primären Diagnosestellung weisen etwa 30% der Patienten mit
Weichteilsarkomen ein Stadium I auf, 30% ein Stadium IIa oder Stadium IIb , 20% ein
Stadium III und 20% ein Stadium IV mit bereits Fernmetastasen auf (Stadieneinteilung der
Intergroup Rhabdomyosarkoma Study (IRS) und der CWS-Studie)(Tunn et al. 2008).
Bei lokalisiertem Tumorstadium eines Weichteilsarkoms ist die Operation die einzig
potenziell kurative Therapieoption..
Seite: 6
Grundsätzlich ist die radikale Resektion mit einem Sicherheitsabstand von 2-3 cm
anzustreben. Wichtiger jedoch als der absolute Sicherheitsabstand ist die Beachtung
anatomischer Grenzschichten (Arbeit et al. 1987, Baldini et al. 1999).
Die bessere und prognostisch gleichwertige, als Standard anzusehende Alternative zu einer
Kompartmentresektion oder Amputation ist die weite Exzision, gefolgt von der Bestrahlung.
Eine verstümmelnde Amputation bei Kinder, Jugendlichen und Erwachsenen mit
Weichteilsarkomen muss aufgrund der Risiko-Adaptierten Therapieplanung (siehe 5) mit
neoadjuvanter Chemotherapie mit oder ohne regionale Hyperthermie, adjuvanter
Chemotherapie oder adjuvanter Bestrahlung nur noch in weniger als 5% durchgeführt
werden.
5.4. Postoperative Strahlentherapie
Eine Vielzahl retrospektiver Studien hat gezeigt, dass die postoperative Strahlentherapie mit
60-70 Gy in der Lage ist bei R1-Resektionen (mikroskopische Tumorresiduen nach
Resektion) lokale Kontrollraten zwischen 72% und 90% unter weitgehendem Erhalt der
Funktionen zu erzielen. Nach den Ergebnissen zweier randomisierter Studien kann die
Indikation zur postoperativen Strahlentherapie bzw. postoperative Brachytherapie nach
lokaler Resektion als etabliert betrachtet werden, ausgenommenT1a G1 und G2 Sarkome
(Pisters et al. 1996, Yang et a. 1998).
5.5 Systemische Chemotherapie
Neoadjuvante und adjuvante Chemotherapien und Chemostrahlentherapieverfahren sollten
nur nach interdisziplinärer Absprache in damit erfahrenen Sarkomzentren, und wenn
möglich, im Kontext von Studien. durchgeführt werden. Dasselbe gilt für die palliative
Chemotherapie. Bei > 30 histopathologischen Unterformen von Weichteilsarkomen orientiert
sich die Selektion der medikamentösen Sarkomtherapie zunehmend an der
histopathologisch und teils auch molekulargenetisch determinierten Diagnose.
6. Sonstige Angaben
Studien zur Therapie von Sarkomen sind u.a. gelistet unter:
http://www.aio-portal.de/index.php?article_id=107
http://www.kinderkrebsinfo.de/e1676/e9032/e1758/e78630/index_ger.html
http://protiv-raka.org/wp-content/uploads/2011/02/protokol_osteosarcoma.pdf
https://ukmhosts.uni-muenster.de/index.php?id=1930
Seite: 7
7. Erkenntnismaterial/Recherche
Ergebnisübersicht der Datenbankrecherche
Tabelle 1
Datum
Datenbank
Suchbegriffe
31.03.2011
(15.04.2011)
31.03.2011
(15.04.2011)
Pubmed
31.03.2011
(15.04.2011)
Pubmed
sarcoma; carboplatin;
etoposide
etoposide
[limits: All Adult: 19+ years]
etoposide; no ewing-sarcoma
[limits: All Adult: 19+ years]
(Recherche)
Pubmed
Anzahl
Treffer
99
Bemerkungen
56
12
s. Anhang 1 und
Tabelle 2
carboplatin +
etoposide plus
andere
Zytostatika (3
Publikationen)
carboplatin +
etoposide plus
andere
Zytostatika und
autologe
Stammzelltranspl
antation (6
Publikationen)
Carboplatin +
etoposide bei
Ewing-Sarkomen
(3 Publikationen)
24.03.2011
EMBASE
bei DIMDI
etoposid AND carboplatin AND
sarcoma
[Filter: English, German,
French, Krebserkrankungen,
Mensch]
867
24.03.2011
EMBASE
bei DIMDI
sarcoma AND clinical trial
NOT paediatric
Mensch]
261
24.03.2011
EMBASE
bei DIMDI
sarcoma AND clinical trial
AND adult
Mensch]
74
Seite: 8
31.03.2011
(18.04.2011)
www.clinical
trials.gov
soft tissue sarcoma and
carboplatin
38
31.03.2011
(18.04.2011)
www.clinical
trials.gov
etoposide
64
31.03.2011
(18.04.2011)
www.clinical
trials.gov
carboplatin and etoposide
21
s. Anhang 3
18.04.2011
Cochrane
Database
soft tissue sarcoma,
etoposide, carboplatin
3
s. Anhang 4
8. Auswahlkriterien für Studien
In die Auswertung sollten Studien einbezogen werden, bei d enen erwachsene Patienten mit
Weichteilsarkomen sowohl in der Erstlinienals auch in der Zwe
itlinientherapie eine
Chemotherapie alleine mit Carboplatin und Etoposid erhalten haben.
9. Ergebnis der Recherche
Zu der im Gutachten gestellten Fragestellung wurden Literaturrecherchen bei PubMed, bei
EMBASE (über DIMDI), bei www.clinicaltrials.gov und in der Cochrane Database
durchgeführt (s. Tabelle 1).
Bei PubMed fanden sich 99 Treffer mit den Suchbegriffen Weichteilsarkome (soft tissue
sarcoma) Carboplatin und Etoposide, die durch Eingabe weiterer Beschränkungen (no
ewing-sarcoma; [limits: All Adult: 19+ years]) auf 12 Treffer reduziert wurden.
Bei genauer Betrachtung dieser 12 Publikationen fand sich keine Arbeit mit der im
Gutachten gestellten Fragestellung über die Behandlung ausschließlich mit Carboplatin und
Etoposid von Erwachsenen mit Weichteilsarkomen (s. Tabelle 2). In 3 Publikationen wurden
Patienten mit Ewing-Sarkomen behandelt ( 1,4,7,8,11), in 5 Arbeiten wurde eine HochdosisChemotherapie mit Stammzell-Transplantation durchgeführt (2,6,9,11,12) und in 2
Publikationen wurden außer Carboplatin und Etoposid noch andere Zytostatika gegeben.
Bei der Literatur-Recherche bei EMBASE (über DIMDI) wurden 867 Treffer unter den
Suchbegriffen Etoposide und Carboplatin und Sarkome (sarcoma) gefunden. Durch
Verknüpfung mit „clinical trial“ und „adult“ wurde diese auf 74 Treffer reduziert. Es fand sich
keine Publikation, die die hier betrachtete Fragestellung über die Behandlung ausschließlich
mit Carboplatin und Etoposid von Erwachsenen mit Weichteilsarkomen behandelt (s. Anhang
2 und Tabelle 3).
Die Recherchen in der Datenbanken „clinicaltrials“ und in der Cochrane Database ergaben
keine aktuelle Studie, in die erwachsene Patienten mit Weichteilsarkomen eingeschlossen
werden und ausschließlich mit einer Chemotherapie bestehend aus Etoposid und
Carboplatin behandelt werden (s. Anhang 3 und Anhang 4).
Zusammengefasst kann festgestellt werden, dass sich in den durchgeführten
Literaturrecherchen keine einzige Publikation befand, in denen erwachsene Patienten mit
Weichteilsarkomen eine Chemotherapie ausschließlich mit Carboplatin und Etoposid
erhalten haben.
Seite: 9
Tabelle 2
Übersicht der Publikationen aus einer Pubmed-Recherche mit den Suchwörtern „sarcoma;
carboplatin; etoposide; no ewing-sarcoma“
Autor
Titel (verkürzt)
Quelle
Van Winkle P
Ifosfamide,Carboplatin,and Pediatric Blood
Cancer 44:338,
etoposide (ICE)
reinduction chemotherapy- 2005-
Whelan JS
Carboplatin-based
chemotherapy
Pediatric Blood
Cancer 43:338,2004
Ewing-Sarkome,
andere Zytostatika
Kasper B
Prophylactic treatment
Support Care
Cancer 12:205,2004
andere Zytostatika
Tanaka K
High-dose chemotherapy
J Orthop Sci
7:477,2002
Ewing-Sarkom
andere Zytostatika
Kushner BH
How effective is doseintensive
J Clin Oncol
19:870,2001
Ewing-Sarkome
andere Zytostatika
Burdach S
Allogeneic and autologous
stem-cell transplantation
Ann
Oncol11:1451,2000
Ewing-Sarkome
andere Zytostatika
Ozkaynak MF
Double-alkylator non-totalbody irradiation
J Clin Oncol
16:937,1998
Kinder
andere Zytostatika
Zoubek A
High-dose chemotherapy
Pediatr Hematol
Oncol 11:613,1994
Kinder
Andere Zytostatika
Burdach S
Myeloablative
radiochemotherapy
J Clin Oncol
11:1482,1993
Ewing-Sarkome
Andere Zytostatika
Emminger W
Is treatment intensification
Bone Marrow
Transplant.
8:119,1991
Kinder
Andere Zytostatika
Brazäo-Silva
MT
Ewing-sarcoma in a child
Braz Dent J
21:74,2010
Ewing-Sarkom,
Kind
Bemerkung/
Begründung für
Nichtberücksichtigung
Kinder,
andere Zytostatika-
Avramova B
Myoablative chemotherapy J BUON
Hochdosis-Therapie
with autologous peripheral 11:433,2006
andere Zytostatika
blood stem cell
transplantation
Wie aus der obigen Tabelle hervorgeht, wurden keine Studien identifiziert, die die
Auswahlkriterien erfüllen und zur Beantwortung der Fragestellung herangezogen werden
könnten.
Seite: 10
10. Studienextraktionsbögen
Es wurden keine Studien in strukturierter Form aufgearbeitet, da sich keine Publikation und
keine Studie in der Literatur gefunden wurde, die die Fragestellung im vorliegenden
Gutachten erfüllt hätten.
11. Bewertungsvorschlag und
12. Fazit
Die Literaturrecherche zu Auswertungen klinischer Studien, die eine Chemotherapie allein
mit Carboplatin und Etoposid bei erwachsenen Patienten mit Weichteilsarkomen untersuchten, ergab keinen Treffer. Nutzen und Risiken einer Chemotherapie allein mit Carboplatin und Etoposid bei erwachsenen Patienten mit Weichteildarkom können deshalb nicht
bewertet werden und diese Behandlung kann nicht zur zulassungsüberschreitenden
Anwendung empfohlen werden.
13. Ergänzendes Fazit
entfällt
14. Bemerkungen
Die Expertengruppe empfiehlt, erwachsene Patienten mit Weichteilsarkomen möglichst in
klinischen Studien zu behandeln. So können neue Erkenntnisse gewonnen werden, die eine
weitere Verbesserung der noch unbefriedigenden Behandlungsergebnisse, insbesondere
im fortgeschrittenen Tumorstadium ermöglichen. Außerdem wird damit ein optimaler
Patientenschutz gewährleistet.
Seite: 11
15. Literaturverzeichnis
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extremity superficial truncal treatment. J Clin Oncol 9:49, 1987
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Onkologie. H.-J. Schmoll. K. Höffken, K. Possinger (Hrsg). 4. Auflage, Springer 2006
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the European and American Osteosarkom Study Group to optimize treatment
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7. Koscielniak, E., Klingebiel, Th. Cooperative Weichteilsarkom Study Group CWS der
GPOH: CWS-guidance. Version 1.5. from 01.07.2009
8. Koscielniak, E., Morgan, M. et al. Soft Tissue Sarcoma in Children. Prognosis and
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9. Krebs in Deutschland 2003-2004. Häufigkeiten und Trends. 6. überarbeitete Auflage.
Robert Koch-Institut (Hrsg) und die Gesellschaft der epidemiologischen Krebsregister
in Deutschland e.V. (Hrsg). Berlin, 2008
10. Pisters, P. W. T., Harrison, G. K. et al. Long-term results of a prospective randomized
trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol 14: 859, 1996
11. Rosenberg, S.A., Tepper, J et al. The treatment of soft tissue sarcomas of the
extremities: prospective randomized evaluations of (1) limb-sparing surgery plus
radiation therapy compared with Amputation and (2) the role of adjuvant
chemotherapy. Ann Surg 196:305, 1982
12. Schütte, J., Budach, V., et al. Weichteilsarkome des Erwachsenen. Leitlinie der
Deutschen Gesellschaft für Hämatologie und Onkologie, 28.6. 2006
13. Tunn, P.-U., Andreou, D. et al. Diagnostik und chirurgische Therapie von
Weichteilsarkomen der Extremitärten. Onkologie 2 :10 ,2008.
14. Wendtner, C.M., Delank, S., Eich, H. Multimodale Therapiekonzept bei
Weichteilsarkomen. Internist 51: 1388, 2010
15. Yang, J.C., Chang, A.E., et al. Randomized prospective study of the benefit of
adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J
Clin Oncol 16: 197, 1998
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Anhang 1
Pubmed 15.04.2011
Search: sarcoma; carboplatin; etoposide; no ewing-sarcoma
Limits Activated: All Adult: 19+ years http://www.ncbi.nlm.nih.gov/pubmed/limits
12 Treffer
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Brazão-Silva MT, Fernandes AV, Faria PR, Cardoso SV, Loyola AM.
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patients with poor-prognosis solid tumors - Bulgarian experience.
Avramova B, Jordanova M, Michailov G, Konstantinov D, Christosova I, Bobev D.
J BUON. 2006 Oct-Dec;11(4):433-8.
PMID:
17309174
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Ifosfamide, carboplatin, and etoposide (ICE) reinduction chemotherapy in a large cohort of
children and adolescents with recurrent/refractory sarcoma: the Children's Cancer Group
(CCG) experience.
Van Winkle P, Angiolillo A, Krailo M, Cheung YK, Anderson B, Davenport V, Reaman G,
Cairo MS.
Pediatr Blood Cancer. 2005 Apr;44(4):338-47.
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Whelan JS, McTiernan A, Kakouri E, Kilby A; London Bone and Soft Tissue Tumour
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Pediatr Blood Cancer. 2004 Sep;43(3):237-42.
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Prophylactic treatment of known ifosfamide-induced encephalopathy for chemotherapy with
high-dose ifosfamide?
Kasper B, Harter C, Meissner J, Bellos F, Krasniqi F, Ho AD, Egerer G.
Support Care Cancer. 2004 Mar;12(3):205-7. Epub 2004 Jan 16.
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High-dose chemotherapy and autologous peripheral blood stem-cell transfusion after
conventional chemotherapy for patients with high-risk Ewing's tumors.
Tanaka K, Matsunobu T, Sakamoto A, Matsuda S, Iwamoto Y.
J Orthop Sci. 2002;7(4):477-82.
PMID:
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Allogeneic and autologous stem-cell transplantation in advanced Ewing tumors. An update
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Kinderspital, Vienna, Austria.
Burdach S, van Kaick B, Laws HJ, Ahrens S, Haase R, Körholz D, Pape H, Dunst J, Kahn T,
Willers R, Engel B, Dirksen U, Kramm C, Nürnberger W, Heyll A, Ladenstein R, Gadner H,
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Double-alkylator non-total-body irradiation regimen with autologous hematopoietic stem-cell
transplantation in pediatric solid tumors.
Ozkaynak MF, Matthay K, Cairo M, Harris RE, Feig S, Reynolds CP, Buckley J, Villablanca
JG, Seeger RC.
J Clin Oncol. 1998 Mar;16(3):937-44.
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High-dose cyclophosphamide, adriamycin, and vincristine (HD-CAV) in children with
recurrent solid tumor.
Zoubek A, Holzinger B, Mann G, Peters C, Emminger W, Perneczky-Hintringer E, Gadner H,
Mostbeck G, Horcher E, Dobrowsky W.
Pediatr Hematol Oncol. 1994 Nov-Dec;11(6):613-23.
PMID:
7857784
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Myeloablative radiochemotherapy and hematopoietic stem-cell rescue in poor-prognosis
Ewing's sarcoma.
Burdach S, Jürgens H, Peters C, Nürnberger W, Mauz-Körholz C, Körholz D, Paulussen M,
Pape H, Dilloo D, Koscielniak E, et al.
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PMID:
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Related citations
Anhang 2
Recherche EMBASE bei DIMDI am 29.03.2011
EMBASE_adult Datum....................: 29.03.2011 Uhrzeit..................: 11:05:00
Ausgabeformat : HTML
gefundene Dokumente : 7
abgesuchte Datenbank(en) : EM47 - EMBASE copyright 2011 Elsevier B.V. -------------------Schlagwörter: etoposid AND carboplatin AND sarcoma AND clinical trial AND adult
Die nachfolgende Verknüpfung der Suchbegriffe wird automatisch generiert:
(((((CT D "etoposid" OR UT="etoposid" OR IT="etoposid" OR SH="etoposid") AND (CT D
"carboplatin" OR UT="carboplatin" OR IT="carboplatin" OR SH="carboplatin")) AND (CT
D "sarcoma" OR UT="sarcoma" OR IT="sarcoma" OR SH="sarcoma")) AND (CT D
"clinical trial" OR UT="clinical trial" OR IT="clinical trial" OR SH="clinical trial")) AND
(CT D "adult" OR UT="adult" OR IT="adult" OR SH="adult")) AND (LA=ENGLISH OR
LA=GERMAN OR LA=FRENCH) AND (pps=Krebserkrankungen OR pps=Mensch)
Volltext online anzeigen
1 von 74
DIMDI: EMBASE (EM47) © 2011 Elsevier B.V.
ND:
EM2010681243
Autoren: Thiery-Vuillemin A; Dobi E; Nguyen T; Royer B; Montange D; Maurina T;
Kalbacher E; Bazan F; Villanueva C; Demarchi M; Chaigneau L; Ivanaj A; Pivot X
Titel:
Duration: Escalation study of oral etoposide with carboplatin in
patients with varied solid tumors
Source:
DOI:
PU:
SU:
Sprache:
AB:
Anti-Cancer Drugs; VOL: 21 (10); p. 958-962 /November 2010/
10.1097/CAD.0b013e32833fc0be
Lippincott Williams and Wilkins
EMBASE
English
Prolonged fractionated oral administration of etoposide may present a theoretical
advantage over intravenous administration of the bolus. This phase I trial was
carried out to determine the recommended duration of oral etoposide in combination
with a fixed dose of carboplatin. Nineteen patients with varied solid tumors, who
were not candidates for standard chemotherapy, were administered an escalating
duration (6, 9 or 12 consecutive days) of oral etoposide (a 25mg capsule three times
daily) combined with carboplatin AUC5 administered on day 1, by a 30 min
intravenous infusion, to define the maximum tolerated dose on the basis of the acute
toxicities that were reported. Etoposide was started on day 2; the cycles repeated
every 28 days until disease progression or toxicity. Pharmacokinetics was carried
out during the two first cycles. The maximum tolerated dose was determined to be
the 12-day treatment level, with two cases of grade 4 neutropenia, grade 3 anemia
and thrombocytopenia. As no severe toxicity occurred with the 9-day treatment
level and in an attempt to explore an optimal combination, a new 10-day treatment
plan was studied in three patients. As onepatient presented dose-limiting toxicity at
that level, five additional patients were included to establish the recommended
regimen. Nonhematological toxicities among all patients were moderate, consisting
of grade 2 nausea and asthenia. No treatment-related death occurred. Objective
responses were observed in four patients and stabilization in three patients.
Pharmacokinetics highlighted no interaction between etoposide and carboplatin.
Fractionated oral etoposide (3× 25 mg/day) for 10 days in combination with
carboplatin AUC 5 presents acceptable toxicity and efficacy. The main toxicity
remains hematological. © 2010 Wolters Kluwer Health | Lippincott Williams &
Wilkins.
2 von 74
ND:
Autoren:
EM2010632795
Srinivasan N; Pakala A; Mukkamalla C; Oswal A
Titel:
Pineal germinoma
Source:
DOI:
PU:
SU:
Sprache:
AB:
Southern Medical Journal; VOL: 103 (10); p. 1031-1037 /October 2010/
10.1097/SMJ.0b013e3181ebeeff
Lippincott Williams and Wilkins
EMBASE
English
Germinomas are gonadal neoplasms that rarely occur extragonadally in the
midline structures of the human body. Newly diagnosed adult cases of pineal
gland germinomas are very rare since most of the cases are diagnosed in the mid
teens. The estimated incidence of this tumor in western countries is between 0.43.4%. Typically, this tumor is diagnosed by its characteristic radiological
appearance alone, supported by tumor marker(s) or by stereotactic biopsy of the
tumor. We are reporting a very unique case of pineal germinoma diagnosed in an
adult at our institute by cerebrospinal fluid cytology with literature review. We
analyzed case reports, literature reviews, and therapy and diagnostic articles about
pineal germinoma in the English literature from 1983 to 2009 through the national
library of medicine, Pubmed, and OVID search engines. We used key words
"pineal germinoma," "pineal gland tumor," "CNS germinoma," and "extragonodal
germinomas" to search for our articles. Copyright © 2010 by The Southern
Medical Association.
3 von 74
ND:
Autoren:
EM2010407908
Kasper B; Scharrenbroich I; Schmitt T; Wuchter P; Dietrich S; Ho AD; Egerer G
Titel:
Consolidation with high-dose chemotherapy and stem cell support
for responding patients with metastatic soft tissue sarcomas:
Prospective, single-institutional phase II study
Source:
DOI:
PU:
SU:
Bone Marrow Transplantation; VOL: 45 (7); p. 1234-1238 /July 2010/
10.1038/bmt.2009.333
Nature Publishing Group
EMBASE
Sprache:
AB:
4 von 74
English
Prognosis of patients with metastatic soft tissue sarcoma remains poor. Whether
high-dose chemotherapy with stem cell support improves the long-term outcome
for these patients is debatable. We present a prospective, single-institutional phase
II study that enrolled 34 soft tissue sarcoma patients with advanced and/or
metastatic disease. After four courses of chemotherapy consisting of doxorubicin
and ifosfamide, responding patients in at least partial response (PR) were treated
with high-dose chemotherapy (n9); all other patients continued chemotherapy for
two more cycles. After standard chemotherapy, PR (n10), stable disease (SD, n6)
and progressive disease (PD, n14) were attained for the evaluable patients.
Twenty-nine patients died and five are alive with the disease. Median PFS was
11.6 months (range 8-15) for patients treated with high-dose chemotherapy (n9) vs
5.6 months (range 0-19) for patients treated with standard chemotherapy. Median
OS was 23.7 months (range 12-34) vs 10.8 months (range 0-39), respectively. The
subgroup of patients treated with high-dose chemotherapy gained significant
survival benefit. Nevertheless, high-dose chemotherapy as a possible
consolidation strategy remains highly investigational. © 2010 Macmillan
Publishers Limited All rights reserved.
ND:
Autoren:
EM2010290130
McDowell HP; Foot ABM; Ellershaw C; Machin D; Giraud C; Bergeron C
Titel:
Outcomes in paediatric metastatic rhabdomyosarcoma: Results of
The International Society of Paediatric Oncology (SIOP) study
MMT-98
Source:
DOI:
PU:
SU:
Sprache:
AB:
European Journal of Cancer; VOL: 46 (9); p. 1588-1595 /June 2010/
10.1016/j.ejca.2010.02.051
Elsevier Ltd
EMBASE
English
Purpose: Results are presented of the SIOP study MMT-98 for paediatric
metastatic rhabdomyosarcoma (RMS), which evaluated intensive chemotherapy
followed by low intensity 'maintenance' chemotherapy in standard risk patients
(SRG). For poor risk patients (PRG), the value of a therapeutic window study,
sequential high dose monotherapy to achieve a complete response (CR) followed
by low dose maintenance chemotherapy was examined. Patients and methods:
From November 1998 to 2005, 146 patients aged 6 months to 18 years with
metastatic RMS were entered. Forty-five were SRG, i.e. age < 10 years and no
bone marrow or bone involvement. Treatment was a 6-drug regimen with local
therapy of surgery and/or radiotherapy followed by maintenance of 9 courses of
vincristine, actinomycin D and cyclophosphamide (VAC). One hundred and one
patients were PRG, i.e. >10 years, or with bone marrow or bone metastases. An
upfront window study, high dose monotherapy, local treatment and then VAC
maintenance therapy were given. Results: With a median follow-up of 1.52 years,
the 3-year event-free survival (EFS) and overall survival (OS) for SRG were
54.92% and 62.14%, respectively, whilst for the PRG 16.17% and 23.17%. The
corresponding adverse hazard ratio (HR) for the PRG was HR = 2.65 (95% CI
1.63-4.31, p-value < 0.001) for EFS and HR = 2.51 (CI 1.53-4.11, p-value <
0.001) for OS. Conclusion: SRG patients' EFS and OS were comparable to those
of previous studies. For PRG patients there was no improvement in survival. ©
2010 Elsevier Ltd. All rights reserved.
5 von 74
ND:
Autoren:
EM2010057776
Fritsch P; Schwinger W; Schwantzer G; Lackner H; Sovinz P; Wendelin G;
Benesch M; Sipurzynski S; Urban C
Titel:
Peripheral blood stem cell mobilization with Pegfilgrastim compared
to Filgrastim in children and young adults with malignancies
Source:
Pediatric Blood and Cancer; VOL: 54 (1); p. 134-137 /January 2010/
http://www3.interscience.wiley.com/cgi-bin/fulltext/122609874/PDFSTART
10.1002/pbc.22304
Wiley-Liss Inc.
EMBASE
English
Background. Pegfilgrastim, the long acting agent of rh-GCSF, has been shown to
be as effective as Filgrastim in children undergoing cytotoxic chemotherapy by
reducing the duration of neutropenia. Recent studies in adults have also shown
that Pegfilgrastim is effective to mobilize CD34+ stem cells, resulting in earlier
peripheral stem cell collections (PSCC). The aim of the study was to compare the
efficacy of Pegfilgrastim with Filgrastim for CD34+ stem cell mobilization in
children. Procedure. Three groups of patients were compared: Group 1: six
patients with Ewing Sarcoma stimulated with Filgrastim; Group 2: five patients
with Ewing Sarcoma, Ependymoma, and Neuroblastoma; Group 3: four patients
with relapsed neoplasm. Patients of Group 2 and 3 were stimulated with
Pegfilgrastim followed by peripheral stem cell collection. Two patients in Group 3
needed further cytokine stimulation with Filgrastim combined with stem cell
factor, Ancestim. Results. In Groups 1-3, a median of 4, 3, and 3 PSCC between
day 12-24, 6-13, and 8-30 were performed, yielding a median of 14.2, 24.0, and
10.3 x106 CD34+ stem cells/kg BW, respectively. Conclusions.
Group 2 data show that stem cell mobilization with Pegfilgrastim in children when
performed during primary or without previous long lasting chemotherapy seems to
produce earlier CD34+ peaks and better CD34+ yields than in Group 1. CD34+
cell mobilization with Pegfilgrastim in Group 3-patients with previous long lasting
chemotherapy was possible. © 2009 Wiley-Liss, Inc.
DOI:
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6 von 74
ND:
Autoren:
EM2010073366
Merchant MS; Mackall CL
Titel:
Current approach to pediatric soft tissue sarcomas
Source:
Oncologist; VOL: 14 (11); p. 1139-1153 /2009/
http://theoncologist.alphamedpress.org/cgi/reprint/14/11/1139
ClinicalTrials.gov-NCT00047372; ClinicalTrials.gov-NCT00077285;
NCT:
DOI:
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7 von 74
ClinicalTrials.gov-NCT00923351
10.1634/theoncologist.2009-0160
AlphaMed Press
EMBASE
English
The development of a new soft tissue lesion in an otherwise healthy child,
adolescent, or young adult can present many challenges for pediatric or medical
oncology teams. Although uncommon, the diagnosis of a soft tissue malignancy
should always be considered in the differential diagnosis of persistent pain, even if
no mass is palpable. The definitive diagnosis and treatment of a soft tissue mass is
aided by timely scans, appropriate biopsy for anatomic and molecular pathology,
and a treatment approach guided by the specific diagnosis. Because pediatric soft
tissue sarcomas are rare, cooperative groups play a crucial role in defining the
standard of care through retrospective series and well-designed prospective
clinical trials. Enrollment of newly diagnosed patients in clinical studies should be
encouraged in order to continue to improve outcomes and understanding of these
rare tumors. This review focuses on the current recommendations for management
of sarcomas that typically occur in the soft tissues of pediatric and young adult
patients. ©AlphaMed Press.
ND:
Autoren:
EM2009352535
Mattke AC; Bailey EJ; Schuck A; Dantonello T; Leuschner I; Klingebiel T;
Treuner J; Koscielniak E
Titel:
Does the time-point of relapse influence outcome in pediatric
rhabdomyosarcomas?
Source:
Pediatric Blood and Cancer; VOL: 52 (7); p. 772-776 /20090701/
10.1002/pbc.21906
Wiley-Liss Inc.
EMBASE
English
Background. Childhood rhabdomyosarcoma (RMS), a soft tissue malignant tumor
of skeletal muscle origin, accounts for approximately 3.5% of the cases of cancer
among children 0-14 years and 2% of the cases among adolescents and young
adults 15-19 years of age. Procedure. We evaluated survival (SUR) after first
relapse depending on the time to relapse (TTR) in RMSs of childhood and
adolescence. Early, intermediate, and late relapsing patients were evaluated for
prognostic risk factors. Results. Two hundred thirty-four patients with RMS
enrolled in the German sarcoma trial CWS-81, CWS-86, CWS-91, and CWS-96
met selection criteria. Of the 234 patients, 35%, 32%, and 33% relapsed within 6
(early), 6-12 (intermediate), and more than 12 (late) months respectively after the
end of primary therapy. Four-year SUR was 12%, 21%, and 41% for early,
intermediate, and late relapse respectively (P<0.001). Four-year SUR after local
DOI:
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relapse was 18% (early), 38% (intermediate), and 49% (late). Embryonal RMS
showed four year SUR of 16%, 30%, and 46% (P<0.001) whereas alveolar
histology showed four year SUR of 8%, 6%, and 23% (P<0.01) for early,
intermediate, and late relapse respectively. Conclusion. TTR has significant
influence on prognosis in relapsed RMS. It influences SUR independent of other
features such as type of relapse, histology, tumor site, primary treatment time or
irradiation in primary treatment. © 2009 Wiley-Liss, Inc.
8 von 74
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Autoren:
EM2009304311
Lieu C; Chow L; Pierson AS; Eckhardt SG; O'Bryant CL; Morrow M; Tran ZV;
Wright JJ; Gore L
Titel:
A phase i study of bortezomib, etoposide and carboplatin in patients
with advanced solid tumors refractory to standard therapy
Source:
DOI:
PU:
SU:
Sprache:
AB:
Investigational New Drugs; VOL: 27 (1); p. 53-62 /February 2009/
10.1007/s10637-008-9154-z
Kluwer Academic Publishers
EMBASE
English
To evaluate the toxicity, pharmacological, and biological properties of the
combination of bortezomib, etoposide, and carboplatin in adults with advanced
solid malignancies. Patients and methods: Patients received escalating doses of
bortezomib, etoposide, and carboplatin every 21 days. Surrogate markers of
angiogenesis were evaluated. Results: Twenty-four patients received 64 courses of
therapy. The most common treatment-related adverse events were
myelosuppression. Dose-limiting grade 3 and 4 neutropenia and thrombocytopenia
were observed when bortezomib was given on days 1, 4, 8, 11. With revised
dosing, the maximum tolerated dose (MTD) of bortezomib 0.75 mg/m² (days 1,
8), etoposide 75 mg/m² (days 1-3), and carboplatin AUC 5 (day 1) was well
tolerated, and are the recommended doses for further studies with this
combination. No objective responses were observed, however stable disease was
noted for greater or equal to four cycles in nine highly refractory patients. © 2008
Springer Science+Business Media, LLC.
9 von 74
ND:
Autoren:
EM2009233696
Ramondetta LM; Johnson AJ; Sun CC; Atkinson N; Smith JA; Jung MS;
Broaddus R; Iyer RB; Burke T
Titel:
Phase 2 trial of mifepristone (RU-486) in advanced or recurrent
endometrioid adenocarcinoma or low-grade endometrial stromal
sarcoma
Source:
Cancer; VOL: 115 (9); p. 1867-1874 /20090501/
10.1002/cncr.24197
DOI:
PU:
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Sprache:
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10 von 74
John Wiley and Sons Inc.
EMBASE
English
English
BACKGROUND: The objective of this study was to determine the efficacy of
mifepristone (RU-486) in women with advanced or recurrent endometrioid
adenocarcinoma or low-grade endometrial stromal sarcoma (LGESS).
METHODS: Mifepristone (RU-486; 200 mg orally) was given daily to patients
with progesterone receptor-positive advanced or recurrent endometrioid
adenocarcinoma or LGESS. Patients were evaluated every 4 weeks for toxicity
and response. Quality-of-life data were obtained using the Memorial Symptom
Assessment Scale and Functional Assessment for Cancer Therapy. RESULTS:
Twelve of 13 enrolled patients were evaluable in the first phase of accrual. Stable
disease was noted in 3 of 12 patients (at 8 weeks, 12 weeks, and >=77 weeks,
respectively), and the median time to disease progression was 48 days. Among the
patients who had stable disease, 2 women had endometrioid endometrial cancer,
and 1 woman had LGESS. No partial or complete responses were observed. The
most frequent grade 1 and 2 toxicities were anorexia, fatigue, and mood
alterations observed in 50%, 50%, and 58% of patients, respectively. The most
common grade 3 toxicities were fatigue and dyspnea observed in 25% and 17% of
patients, respectively. One patient experienced grade 4 dyspnea. Thirty-three
percent of patients had asymptomatic elevations of corticotropin. No serious
treatment-related adverse events occurred. There were no significant changes in
quality of life. CONCLUSIONS: Single-agent mifepristone used in the treatment
of recurrent endometrioid adenocarcinoma or LGESS resulted in a stable disease
rate of 25%. One patient who had a biopsy-positive disease recurrence remained
stable at 77 weeks. Although mifepristone was tolerated well, as a single agent, it
provided limited response as a single agent in women with progesterone receptorpositive uterine tumors. Recently, was been recognized that biologic agents used
as single agents may result only in stable disease unless they are combined with
cytotoxic agents. The authors concluded that further research into the best mode of
application for mifepristone in the treatment of endometrial cancer is needed. ©
2009 American Cancer Society.
ND:
Autoren:
EM2008566385
Bielack SS; Carrle D; Hardes J; Schuck A; Paulussen M
Titel:
Bone tumors in adolescents and young adults
Source:
DOI:
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Sprache:
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AB:
Current Treatment Options in Oncology; VOL: 9 (1); p. 67-80 /2008/
10.1007/s11864-008-0057-1
Springer New York LLC
EMBASE
English
English
Bone tumors, particularly osteosarcomas and members of the Ewing Sarcoma
Family of Tumors (ESFT), are typical malignancies of adolescents and young
adults. Current diagnostic and therapeutic guidelines for patients of all ages were
developed in this specific age group. The aim of bone sarcoma therapy should be
to cure the patient from both the primary tumor and all (micro-)metastatic deposits
while maintaining as much (extremity) function and causing as few treatmentspecific late effects as possible. Bone sarcoma therapy requires close
multidisciplinary cooperation. Usually, it consists of induction chemotherapy,
followed by local therapy of the primary tumor (and, if present, primary
metastases) and further, adjuvant chemotherapy. Local treatment for osteosarcoma
should be surgery whenever feasible. Surgery is also gaining importance in ESFT,
which was long considered a domain of radiotherapy. Modern reconstructive
techniques continue to expand the indications for limb salvage, particularly for
patients who have not yet reached skeletal maturity. Treatment within the
framework of prospective, multi-institutional trials should be considered standard
of care not only for children, but also for affected adolescents and (young) adults.
Such trials are essential in guaranteeing that all patients have access to appropriate
care and that progress from biological studies can be translated into prognostic
improvements without undue delay. The rarity of bone sarcomas increasingly
requires trials to be multinational. © Current Medicine Group LLC 2008.
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EM2008494218
Weitberg AB
Titel:
A phase I/II trial of beta-(1,3)/(1,6) D-glucan in the treatment of
patients with advanced malignancies receiving chemotherapy
Source:
ANR:
DOI:
PU:
SU:
Sprache:
AB:
Journal of Experimental and Clinical Cancer Research; VOL: 27 (1) /2008/
40
10.1186/1756-9966-27-40
BioMed Central Ltd.
EMBASE
English
beta -(1,3)/(1,6) D-glucan, a component of the fungal cell wall, has been shown to
stimulate the immune system, enhance hematopoiesis, amplify killing of
opsonized tumor cells and increase neutrophil chemotaxis and adhesion. In view
of these attributes, the beta -glucans should be studied for both their therapeutic
efficacy in patients with cancer as well as an adjunctive therapy in patients
receiving chemotherapy as a maneuver to limit suppression of hematopoiesis. In
this study, twenty patients with advanced malignancies receiving chemotherapy
were given a beta -(1,3)/(1,6) D-glucan preparation (MacroForce plus IP6,
ImmuDyne, Inc.) and monitored for tolerability and effect on hematopoiesis. Our
results lead us to conclude that beta -glucan is well-tolerated in cancer patients
receiving chemotherapy, may have a beneficial effect on hematopoiesis in these
patients and should be studied further, especially in patients with chronic
lymphocytic leukemia and lymphoma. © 2008 Weitberg; licensee BioMed Central
Ltd.
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EM2008251453
Pearson AD; Pinkerton CR; Lewis IJ; Imeson J; Ellershaw C; Machin D
Titel:
High-dose rapid and standard induction chemotherapy for patients
aged over 1 year with stage 4 neuroblastoma: a randomised trial
Source:
NCT:
DOI:
SU:
Sprache:
AB:
The Lancet Oncology; VOL: 9 (3); p. 247-256 /200803/
ClinicalTrials.gov-NCT00365755
10.1016/S1470-2045(08)70069-X
EMBASE
English
Background: The current standard treatment for patients with high-risk
neuroblastoma includes initial induction chemotherapy with a 21-day interval
between induction treatments. We aimed to assess whether an intensive
chemotherapy protocol that had a 10-day interval between treatments would
improve event-free survival (EFS) in patients aged 1 year or over with high-risk
neuroblastoma. Methods: Between Oct 30, 1990, and March 18, 1999, patients
with stage 4 neuroblastoma who had not received previous chemotherapy were
enrolled from 29 centres in Europe. Patients were randomly assigned to rapid
treatment (cisplatin [C], vincristine [O], carboplatin [J], etoposide [E], and
cyclophosphamide [C], known as COJEC) or standard treatment (vincristine [O],
cisplatin [P], etoposide [E], and cyclophosphamide [C], ie, OPEC, alternated with
vincristine [O], carboplatin [J], etoposide [E], and cyclophosphamide [C], ie,
OJEC). Both regimens used the same total cumulative doses of each drug (except
vincristine), but the dose intensity of the rapid regimen was 1·8-times higher than
that of the standard regimen. The standard regimen was given every 21 days if
patients showed haematological recovery, whereas the rapid regimen was given
every 10 days irrespective of haematological recovery. Response to chemotherapy
was assessed according to the conventional International Neuroblastoma Response
Criteria (INRC). In responders, surgical excision of the primary tumour was
attempted, followed by myeloablation (with 200 mg/m² of melphalan) and
haemopoietic stem-cell rescue. Primary endpoints were 3-year, 5-year, and 10year EFS. Data were analysed by intention to treat. This trial is registered on the
clinical trials site of the US National Cancer Institute website, number
NCT00365755, and also as EU-20592 and CCLG-NB-1990-11. Findings: 262
patients, of median age 2·95 years (range 1·03-20·97), were randomly assigned132 patients to standard and 130 patients to rapid treatment. 111 patients in the
standard group and 109 patients in the rapid group completed chemotherapy.
Chemotherapy doses were recorded for 123 patients in the standard group and 126
patients in the rapid group. 97 of 123 (79%) patients in the standard group and 84
of 126 (67%) patients in the rapid group received at least 90% of the scheduled
chemotherapy, and the relative dose intensity was 1·94 compared with the
standard regimen. 3-year EFS was 24·2% for patients in the standard group and
31·0% for those in the rapid group (hazard ratio [HR] 0·86 [95% CI 0·66-1·14],
p=0·30. 5-year EFS was 18·2% in the standard group and 30·2% in the rapid
group, representing a difference of 12·0% (1·8 to 22·3), p=0·022. 10-year EFS was
18·2% in the standard group and 27·1% in the rapid group, representing a
difference of 8·9% (-1·2 to 19·0), p=0·085. Myeloablation was given a median of
55 days earlier in patients assigned rapid treatment than those assigned standard
treatment. Infective complications (numbers of patients with febrile neutropenia
and septicaemia, and if given, time on antibiotic and antifungal treatment) and
time in hospital were greater with rapid treatment. Occurrence of fungal infection
was the same in both regimens. Interpretation: Dose intensity can be increased
with a rapid induction regimen in patients with high-risk neuroblastoma. There
was no significant difference in OS between the rapid and standard regimens at 5
years and 10 years. However, an increasing difference in EFS after 3 years
suggests that the efficacy of the rapid regimen is better than the standard regimen.
A rapid induction regimen enables myeloablation to be given much earlier, which
might contribute to a better outcome. © 2008 Elsevier Ltd. All rights reserved.
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EM2008172897
Schuster MW; Shore TB; Harpel JG; Greenberg J; Jalilizeinali B; Possley S;
Gerwien RW; Hahne W; Halvorsen Y-DC
Titel:
Safety and tolerability of velafermin (CG53135-05) in patients
receiving high-dose chemotherapy and autologous peripheral blood
stem cell transplant
Source:
DOI:
SU:
Sprache:
AB:
Supportive Care in Cancer; VOL: 16 (5); p. 477-483 /200805/
10.1007/s00520-007-0325-9
EMBASE
English
Goals of work: The objective of this study was to evaluate the safety and
tolerability of velafermin in patients at risk of developing severe oral mucositis
(OM) from chemotherapy. Materials and methods: This study was a single-center,
open-label, single-dose escalation, phase I trial in patients undergoing high-dose
chemotherapy (HDCT) and autologous peripheral blood stem cell transplant
(PBSCT). Velafermin was administered 24 h after stem cell infusion as a single
intravenous dose infused over 15 min. Clinical safety variables were assessed and
OM status scored daily for 30 days using the World Health Organization (WHO)
grading scale. Main results: Thirty patients were treated with velafermin at doses
of 0.03 (n=10), 0.1 (n=10), 0.2 (n=8), or 0.33 mg/kg (n=2). Patients were
diagnosed with multiple myeloma (n=16), non-Hodgkin's lymphoma (n=12), acute
myelogenous leukemia (n=1), or desmoplasmic round cell tumor (n=1).
Velafermin was well tolerated at doses up to 0.2 mg/kg. There were no drugrelated serious adverse events. No patient discontinued because of adverse events;
however, two patients administered 0.33 mg/kg developed adverse reactions
immediately after infusion of the study drug. No other patients were treated at this
dose level. The most frequent (>35% of patients) treatment-emergent adverse
events were diarrhea, fatigue, pyrexia, vomiting, and nausea. Most adverse events
were mild or moderate and resolved the same day without sequelae. Eight (27%)
patients developed WHO grade 3 or 4 OM during the study; seven of these
patients received high-dose melphalan as a conditioning regimen. Conclusion:
Velafermin was well tolerated by autologous PBSCT patients at doses up to 0.2
mg/kg. © 2007 Springer-Verlag.
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EM2008170047
Ozkaynak MF; Sahdev I; Gross TG; Levine JE; Cheerva AC; Richards MK;
Rozans MK; Shaw PJ; Kadota RP
Titel:
A pilot study of addition of amifostine to melphalan, carboplatin,
etoposide, and cyclophosphamide with autologous hematopoietic
stem cell transplantation in pediatric solid tumors - A pediatric
blood and marrow transplant consortium study
Source:
DOI:
SU:
Sprache:
AB:
Journal of Pediatric Hematology/Oncology; VOL: 30 (3); p. 204-209 /200803/
10.1097/MPH.0b013e318162bd0c
EMBASE
English
Limited information is available regarding the use of amifostine in pediatric
hematopoietic stem cell transplant (HSCT) patients. Melphalan, carboplatin,
etoposide ± cyclophosphamide is a commonly used preparatory regimen in
pediatric solid tumor HSCT. Therefore, we decided to determine the feasibility of
the addition of amifostine (750 mg/m b.i.d. ×4 d) to melphalan (200 mg/m),
carboplatin (1200 mg/m), and etoposide (800 mg/m) (level 1) and escalating doses
of cyclophosphamide (3000 mg/m and 3800 mg/m, levels 2 and 3, respectively)
followed by autologous HSCT. Thirty-two patients with a variety of pediatric
solid tumors were studied. Seventeen patients were accrued at level 1, 9 at level 2,
and 6 at level 3. Major toxicities during the administration of the preparatory
regimen were hypocalcemia, emesis, and hypotension. Hypocalcemia required
aggressive calcium supplementation during the conditioning phase. No dose
limiting toxicities were encountered at level 3. Amifostine at 750 mg/m b.i.d. for 4
days can be administered with a double alkylator regimen consisting of melphalan
(200 mg/m), cyclophosphamide (up to 3800 mg/m), carboplatin (1200 mg/m), and
etoposide (800 mg/m) with manageable toxicities. © 2008 Lippincott Williams &
Wilkins, Inc.
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EM2007597146
Dohnal AM; Witt V; Hügel H; Holter W; Gadner H; Felzmann T
Titel:
Phase I study of tumor Ag-loaded IL-12 secreting semi-mature DC
for the treatment of pediatric cancer
Source:
DOI:
SU:
Sprache:
AB:
Cytotherapy; VOL: 9 (8); p. 755-770 /2007/
10.1080/14653240701589221
EMBASE
English
Background: Cancer vaccines employing DC in their capacity as APC have been
tolerated well and have shown some efficacy in clinical studies. IL-12, a cytokine
critical for type 1 T-helper (Th1) lymphocyte and cytotoxic T-lymphocyte (CTL)
differentiation, when released from a DC-based cancer vaccine, may support the
generation of a cellular T-cell response. Methods: We applied tumor cell lysate
plus keyhole limpet hemocyanin (KLH)-loaded and 48-h lipopolysaccharide
(LPS) plus IFN- gamma -stimulated fully mature DC, which do not release IL-12,
subcutaneously to eight patients, and maximally 6-h stimulated semi-mature (sm)
DC, which are potent producers of IL-12, subcutaneously (n=6) or intranodally
(n=8) as a cancer vaccine to patients suffering from advanced solid pediatric
malignancies. Results: No serious adverse events were observed following
application of IL-12-releasing smDC. Following immunization the majority of
patients responded positively to KLH in a delayed-type hypersensitivity (DTH)
test. In addition, three of six intranodally treated patients responded to the tumor
Ag in the DTH test. Discussion: We conclude that treatment with a DC-based
cancer vaccine enabled to release the immune regulatory cytokine IL-12 is safe
and feasible and has the potential to induce a cellular immune response in
pediatric cancer patients.
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EM2007499525
Nieto Y; Aldaz A; Rifón J; Pérez-Calvo J; Zafra A; Zufia L; Viúdez A; Viteri S;
Aramendía JM; Aristu J; Centeno C; Moreno M; Sayar O; Hernández M
Titel:
Phase I and Pharmacokinetic Study of Gemcitabine Administered at
Fixed-Dose Rate, Combined with Docetaxel/Melphalan/Carboplatin,
with Autologous Hematopoietic Progenitor-Cell Support, in Patients
with Advanced Refractory Tumors
Source:
Biology of Blood and Marrow Transplantation; VOL: 13 (11); p. 1324-1337
/200711/
10.1016/j.bbmt.2007.07.008
EMBASE
English
The purpose of this trial was to define the maximum tolerated duration (MTD),
dose-limiting toxicity (DLT), regimen-related toxicities (RRT), and
pharmacokinetics of gemcitabine infused at a fixed dose rate (FDR) of 10
mg/m²/min, combined with docetaxel/melphalan/carboplatin, using autologous
stem cell transplantation (ASCT). The duration of gemcitabine infusion was
incrementally escalated as a single treatment on day -6 or as 4 daily infusions on
days -5 to -2. Gemcitabine was followed by docetaxel (300 or 350 mg/m²) on day
-5, and then melphalan (50 mg/m²/day) and carboplatin (333 mg/m²/day) on days 4 to -2. Fifty-two patients with refractory tumors were accrued with a median age
of 40 (range: 6-66), a median of 3 (1-6) prior chemotherapy regimens, and 3 (1-7)
organs involved. The gemcitabine MTD was defined at 20 hours (total dose
12,000 mg/m²) on both schedules. The DLT was enteritis. Three patients died
from aspiration, catheter-related sepsis, and enteritis, respectively. The tumor
response rate was 91%, with 50% complete responses. At current 2-year median
follow-up, the event-free and overall survival (EFS, OS) rates are 54% (median 26
months) and 79% (median not reached), respectively. Gemcitabine area under the
curve (AUC), but not clearance, increased linearly with infusion duration, and
correlated with grade 3 RRT. Docetaxel showed a linear increase of its AUC and
similar clearance compared with prior reports at lower doses. In conclusion,
ASCT-supported infusions of gemcitabine at FDR could be prolonged up to 20
hours. The resulting gemcitabine/docetaxel/melphalan/carboplatin combination
DOI:
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was highly active in refractory cancers and should be further tested in diseasespecific trials. © 2007 American Society for Blood and Marrow Transplantation.
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EM2007493416
Syed R; Bomanji JB; Nagabhushan N; Kayani I; Groves A; Waddington W;
Cassoni A; Ell PJ
Titel:
186Re-HEDP in the treatment of patients with
inoperable osteosarcoma
Source:
Journal of Nuclear Medicine; VOL: 47 (12); p. 1927-1935 /20061201/
http://jnm.snmjournals.org/cgi/reprint/47/12/1927
EMBASE
English
The aim of this study was to examine the safety and efficacy of
186Re-hydroxyethylidene diphosphonate (HEDP) as an adjuvant to
external-beam radiotherapy (EBRT) in the treatment of patients with
osteosarcoma. Methods: Thirteen patients (9 male, 4 female; age range, 12-42 y)
were treated with combination chemotherapy (standard U.K. protocol) and
186Re-HEDP therapy (18.5 MBq/kg, intravenously), followed by
EBRT. A full blood count; liver function test; and measurements of urea and
electrolytes, glomerular filtration rate, and left ventricular function were
performed on all patients before and after therapy. Tumor volume and
composition were obtained from CT or MRI data. Dosimetric calculations were
performed using the MIRD formalism. Results: Of the 13 patients, 1 is still under
follow-up. The median survival time was 36 mo (range, 12-216 mo) from
diagnosis and 5 mo(range, 1-60 mo) from the last 186Re-HEDP
treatment. The mean tumor dose delivered with 186Re-HEDP was
calculated to be 5.8 Gy (range, 0.5-16 Gy). CT and MRI revealed the tumors
tohave a complex structure, comprising "ossified," "partially calcified," and "softtissue" components. Posttherapy scans showed a heterogeneous distribution of
186Re-HEDP in the tumor mass: Although the "soft-tissue"
component showed minimal uptake of the therapeutic dose, the "ossified
component" showed intense uptake. The 3 long-term survivors in whom tumor
sterilization was achieved received calculated mean tumor doses in the range of
2.0-3.1 Gy, which was believed to be an underestimate of the actual tumor doses
delivered. Conclusion: This study indicates that a simple approach to tumor
dosimetry based on mean tumor dose is inappropriate because it may
underestimate the dose delivered to these heterogeneous tumors. The data also
indicate that EBRT combined with a standard dose of 18.5 MBq/kg of
186Re-HEDP does not provide a sufficient dose to achieve tumor
sterilization. A dose estimation technique is required that is based on the
determination of tumor dose at the individual voxel level and that is able to
represent the heterogeneous uptake observed in these complex tumor structures
with highly nonuniform composition. This, coupled with individualized dose
escalation, may then achieve the goal of tumor sterilization. Copyright © 2006 by
the Society of Nuclear Medicine, Inc.
SU:
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AB:
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EM2007186036
Seibel NL; Krailo M; Chen Z; Healey J; Breitfeld PP; Drachtman R; Greffe B;
Nachman J; Nadel H; Sato JK; Meyers PA; Reaman GH
Titel:
Upfront window trial of topotecan in previously untreated children
and adolescents with poor prognosis metastatic osteosarcoma:
Children's Cancer Group (CCG) 7943
Source:
DOI:
SU:
Sprache:
AB:
Cancer; VOL: 109 (8); p. 1646-1653 /20070415/
10.1002/cncr.22553
EMBASE
English
BACKGROUND. Patients with metastatic osteosarcoma have a poor prognosis.
The objectives of the study were to determine the antitumor activity and toxicity
of topotecan (daily x5) in newly diagnosed patients with metastatic osteosarcoma
followed by chemotherapy (ifosfamide, carboplatin, etoposide [ICE], alternating
with cisplatin and doxorubicin [CD]). METHODS. Newly diagnosed patients
(=<30 years of age) with extensive metastatic disease (primary and >=5
pulmonary nodules and/or bone metastases) with normal hepatic, renal, and
cardiac function were eligible. Patients were eligible to receive further topotecan
after standard chemotherapy if they exhibited a response. Twenty-eight patients
were enrolled. Seventeen had metastases to the lung only and 11 had metastases to
the bone or multiple sites. Of 28 patients enrolled, 27 could be evaluated for
response. A limited dose escalation was incorporated. RESULTS. No responses
were seen in the 11 patients treated at 3 mg/m²/day. One partial response (PR) and
1 clinical response (CLR) were reported among 15 patients who received
topotecan at 3.5 mg/m²/day. No dose-limiting toxicity was observed. Principal
nondose-limiting toxicities were hematologic and gastrointestinal. The 2- and 5year event-free survival rates were low, 7% and 4%, respectively, but the 2- and 5year overall survival rates were 44% and 22%, respectively. CONCLUSIONS.
Topotecan at dose of 3.5 mg/m²/day can be safely administered upfront to newly
diagnosed patients without excessive toxicity. Insufficient activity was seen with
topotecan in this schedule to warrant further studies in osteosarcoma. The
combination of ICE and CD was tolerable when delivered after initial topotecan
therapy. © 2007 American Cancer Society.
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EM2007183124
Schlemmer M; Wendtner C-M; Falk M; Abdel-Rahman S; Licht T; Baumert J;
Straka C; Hentrich M; Salat C; Hiddemann W; Issels R-D
Titel:
Efficacy of consolidation high-dose chemotherapy with ifosfamide,
carboplatin and etoposide (HD-ICE) followed by autologous
peripheral blood stem cell rescue in chemosensitive patients with
metastatic soft tissue sarcomas
Source:
DOI:
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Oncology; VOL: 71 (1-2); p. 32-39 /200704/
10.1159/000100447
EMBASE
English
Background: Prognosis of patients with metastatic soft tissue sarcomas (MSTS) is
poor even after response to doxorubicin-based chemotherapy. We report phase II
data of high-dose chemotherapy and peripheral blood stem cell (PBSC) rescue in
patients with MSTS responding to AI-G chemotherapy. Patients and Methods:
From 1997 to 2002, 55 patients with MSTS were prospectively treated with 4
cycles of AI-G (doxorubicin 75 mg/m², ifosfamide 6 g/m ² with G-CSF support).
Responders received 2 further cycles of AI-G with collection of PBSCs. Highdose chemotherapy consisted of ifosfamide 12 g/m², carboplatin 1.2 g/m² and
etoposide 1.2 g/m ² (HD-ICE) followed by reinfusion of PBSCs. Results: Twentyone of 55 patients (38%) were assessed as responders (3 complete response, 18
partial response). All but 2 patients refusing treatment received high-dose
chemotherapy with PBSC rescue leading to grade IV hematologic toxicity without
severe infections in all patients. No toxic death occurred. After a median followup time of 30 months, the median progression-free time was 12 months and
survival time was 22 months for the entire group. By intent-to-treat analysis the
probability of 5-year progression-free survival was significantly higher for
patients allocated to HD-ICE compared to patients receiving second-line
chemotherapy after failure of AI-G (14 vs. 3%; p = 0.003). The estimated 5-year
overall survival between the 2 groups was different (27% vs. not reached) but did
not reach significance (p = 0.08). Conclusion: HD-ICE is feasible and promising
in patients with chemosensitive MSTS. A randomized phase III trial is warranted
to further define the role of HD-ICE as consolidation treatment in these patients.
Copyright © 2006 S. Karger AG.
ND:
Autoren:
EM2007041975
Fine RL; Shah SS; Moulton TA; Yu I-R; Fogelman DR; Richardson M; Burris
HA; Samuels BL; Assanasen C; Gorroochurn P; Hibshoosh H; Orjuela M; Garvin
J; Goldman FD; Dubovsky D; Walterhouse D; Halligan G
Titel:
Androgen and c-Kit receptors in desmoplastic small round cell
tumors resistant to chemotherapy: Novel targets for therapy
Source:
DOI:
SU:
Sprache:
AB:
Cancer Chemotherapy and Pharmacology; VOL: 59 (4); p. 429-437 /200703/
10.1007/s00280-006-0280-z
EMBASE
English
Purpose: Desmoplastic small round cell tumor (DSRCT) is a highly fatal, mainly
peritoneal cell origin cancer which predominantly affects young adult males. This
predilection in young males led us to examine the role of androgen receptors
(AR), testosterone, and growth factors in the biology of DSRCT. Methods: Slides
were prepared from 27 multi-institutional patients all with end-stage DSRCT.
Slides were stained for AR, c-Kit, various growth factors, and drug resistanceassociated proteins. Immunohistochemical (IHC) expression was scored semiquantitatively. Western blot and MTT studies were performed to validate the IHC
findings of over-expression of the AR and its functional status by stimulation of
growth by dihydrotestosterone, respectively. Six patients with positive AR status
were treated solely with combined androgen blockade (CAB) as used for prostate
cancer. Results: Twenty-two patients were male (81%) and five were female
(19%) with a median age at diagnosis of 23. All patients had failed at least two
prior multi-agent chemotherapy regimens and 44% had progressed after
autologous stem cell transplant. DSRCT samples from 10 of 27 patients were
>=2+ IHC positive for AR (37%,P = 0.0045) and 7 of 20 patients were >=2+ IHC
positive for c-Kit (35%, P = 0.018). We found elevated IHC expression of GST-pi,
MRP and thymidylate synthase in smaller subsets of patients. In vitro studies for
AR by Western blot and stimulation of growth by dihydrotestosterone in MTT
assays suggest that the AR in DSRCT cells is functional. Six patients with positive
AR status were treated with CAB alone and three of six attained clinical benefit
(1-PR, 1-MR, 1-SD) in a range of 3-4 months. The three patients who responded
to CAB had normal testosterone levels before CAB, while the three who did not
respond to CAB had baseline castrate levels of testosterone. Conclusions: DSRCT
has significant IHC expression of AR and c-Kit in heavily pre-treated patients.
The presence of significant AR expression in 37% suggests that these patients
could possibly respond to CAB. The significance of c-Kit expression in 35% of
DSRCT patients is unknown and warrants further investigation. © 2006 SpringerVerlag.
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EM2006625419
Wagner LM; McAllister N; Goldsby RE; Rausen AR; McNall-Knapp RY;
McCarville MB; Albritton K
Titel:
Temozolomide and intravenous irinotecan for treatment of advanced
Ewing sarcoma
Source:
DOI:
SU:
Sprache:
AB:
10.1002/pbc.20697
EMBASE
English
Background. Preclinical models show sequence-dependent synergy with the
combination of temozolomide and irinotecan, and a Phase I trial has demonstrated
the combination to be tolerable and active in children with relapsed solid tumors.
Because responses were seen in patients with Ewing sarcoma (ES) on that trial,
additional patients were treated with this combination following study completion.
Procedure. We reviewed data from all ES patients treated with temozolomide and
irinotecan at four institutions, including seven patients treated on the above Phase
I trial. Results. Sixteen patients received a total of 95 courses, with a median of
five courses per patient. All patients had either progressive disease (PD) during
initial therapy (n = 5) or relapse within 2 years of diagnosis (n = 11). Twelve
patients had metastatic disease at diagnosis, including 5 with bone and/or marrow
metastases. Patients received oral temozolomide 100 mg/m²/day on days 1-5 plus
intravenous irinotecan 10-20 mg/m²/day on days 1-5 and 8-12, with courses
repeated every 21-28 days. We observed 1 complete, 3 partial, and 3 minor
responses in 14 evaluable patients, with a median duration of response of 30
weeks. Planned 21-day courses were tolerable and no more toxic than 28-day
courses. Myelosuppression was minimal despite heavy pretreatment. Grade 3-4
diarrhea occurred in 11% of courses and was related to higher irinotecan doses.
Over 600 irinotecan doses were administered uneventfully at home. Conclusions.
Temozolomicle and protracted intravenous irinotecan given in 21-day courses was
tolerable and active in patients with advanced ES. Home administration of
irinotecan with temozolomide was safe and is reasonable palliative therapy. A
formal Phase II study using a uniform dose and schedule is warranted to better
define activity. © 2005 Wiley-Liss, Inc.
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EM2006602514
Schneider B; Fukunaga A; Murry D; Yoder C; Fife K; Foster A; Rosenberg L;
Kelich S; Li L; Sweeney C
Titel:
A phase I, pharmacokinetic and pharmacodynamic dose escalation
trial of weekly paclitaxel with interferon- alpha 2b in patients with
solid tumors
Source:
DOI:
SU:
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AB:
10.1007/s00280-006-0264-z
EMBASE
English
Purpose: Paclitaxel and interferon have demonstrated anti-angiogenic activity in
vitro and in vivo. The toxicity, pharmacokinetics, and pharmacodynamics of
paclitaxel with interferon- alpha 2b (IFN- alpha 2b) were assessed in patients with
solid tumors to assess the feasibility of this novel anti-angiogenic regimen.
Methods: IFN- alpha 2b (1 million units) was administered twice daily by
subcutaneous injection. Paclitaxel was given weekly over 1 h starting at 30 mg/m²
and increased to 50 mg/m². Cycles were repeated every 4 weeks. Results:
Nineteen patients with a variety of solid tumors were enrolled. Dose-limiting
toxicity in cycle 1 was observed at 50 mg/m². Eleven patients were treated at 40
mg/m² with no undue toxicity. Pharmacokinetic parameter comparison studies
were completed in 11 patients who received days 1 and 29 paclitaxel. Mean
paclitaxel clearance and area under the curve (0- infinity ) were not statistically
different from days 1 to 29. There was a 50% increase in the average
C<inf>max</inf> from days 1 to 29. There was also a 73% decrease of matrix
metalloproteinase-9 (MMP-9) levels in these 11 patients from days 1 to 29 (p <
0.0005). All three patients with cutaneous angiosarcomas experienced clinically
meaningful remissions. In addition, minor responses were observed in one patient
with heavily pretreated ovarian cancer and another with adrenocortical carcinoma.
Conclusion: This trial details the inability to dose escalate to the maximum
tolerated dose of weekly paclitaxel when combined with low-dose interferon.
However, this low-dose regimen caused a significant decrease in MMP-9 and
demonstrated anti-cancer activity in cutaneous angiosarcomas. © 2006 SpringerVerlag.
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EM2006583642
McTiernan AM; Cassoni AM; Driver D; Michelagnoli MP; Kilby AM; Whelan JS
Titel:
Improving outcomes after relapse in Ewing's sarcoma: Analysis of
114 patients from a single institution
Source:
NCT:
ANR:
DOI:
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Sarcoma; VOL: 2006 /2006/
ISRCTN-61438620
83548
10.1155/SRCM/2006/83548
EMBASE
English
The outcome for patients with relapsed Ewing's sarcoma is poor. A
retrospectiveanalysis was carried out to identify factors associated with improved
survival.Between 1992 and 2002, 114 patients presented with relapsed or
progressive disease.Median time to progression/relapse was 13 months (range, 2128). Treatment atrelapse included high dose treatment (HDT) in 29 patients, and
surgery or definitiveradiotherapy in 29. 2 and 5-year post relapse survival (PRS)
was 23.5% and 15.2%,respectively. In multivariate analysis, the most significant
factors associated withimproved survival were disease confined locally or to the
lungs (2-year PRS, 40%versus 6%; P<.001), relapse >18 months from diagnosis
(2-year PRS, 53% versus8%; P<.001), HDT at relapse (2-year PRS, 62% versus
11%; P<.001), and surgeryand/or radiotherapy at relapse (2-year PRS, 51% versus
14%; P<.001). First treatment failure in Ewing's sarcoma is mostly fatal. Improved
survival can beachieved in selective patients with aggressive treatment. These
improvements areconfined to those without bone or bone marrow metastases.
Copyright © 2006 Anne M. McTiernan et al.
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EM2006498992
Pedrazzoli P; Ledermann JA; Lotz J-P; Leyvraz S; Aglietta M; Rosti G;
Champion KM; Secondino S; Selle F; Ketterer N; Grignani G; Siena S; Demirer T
Titel:
High dose chemotherapy with autologous hematopoietic stem cell
support for solid tumors other than breast cancer in adults
Source:
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Annals of Oncology; VOL: 17 (10); p. 1479-1488 /200610/
10.1093/annonc/mdl044
EMBASE
English
Since the early 1980s high dose chemotherapy with autologous hematopoietic
stem cell support was adopted by many oncologists as a potentially curative
option for solid tumors, supported by a strong rationale from laboratory studies
and apparently convincing results of early phase II studies. As a result, the number
and size of randomized trials comparing this approach with conventional
chemotherapy initiated (and often abandoned before completion) to prove or
disprove its value was largely insufficient. In fact, with the possible exception of
breast carcinoma, the benefit of a greater escalation of dose of chemotherapy with
stem cell support in solid tumors is still unsettled and many oncologists believe
that this approach should cease. In this article, we critically review and comment
on the data from studies of high dose chemotherapy so far reported in adult
patients with small cell lung cancer, ovarian cancer, germ cell tumors and
sarcomas. © 2006 Oxford University Press.
25 von 74
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EM2006470220
Frickhofen N; Berdel WE; Opri F; Haas R; Schneeweiss A; Sandherr M; Kuhn W;
Hossfeld DK; Thomssen C; Heimpel H; Kreienberg R; Hinke A; Möbus V
Titel:
Phase I/II trial of multicycle high-dose chemotherapy with
peripheral blood stem cell support for treatment of advanced
ovarian cancer
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Bone Marrow Transplantation; VOL: 38 (7); p. 493-499 /200610/
10.1038/sj.bmt.1705472
EMBASE
English
Ovarian cancer is chemosensitive, but most patients with advanced disease die
from tumor progression. As 25% of the patients can be cured by chemotherapy, it
is reasonable to evaluate high-dose chemotherapy (HDCT). Forty-eight patients
with untreated ovarian cancer were entered in a multicenter phase I/II trial of
multicycle HDCT. Median age was 46 (19-59 years); International Federation of
Gynecology and Obstetrics-stage was III in 79% and IV in 21%; 31% had residual
disease > 1 cm after surgery. Two courses of induction/mobilization therapy with
cyclophosphamide (250 mg/m²) and paclitaxel (250 mg/m²) were used to collect
peripheral blood stem cells. HDCT consisted of two courses of carboplatin (area
under curve (AUC) 18-22) and paclitaxel followed by one course of carboplatin
and melphalan (140 mg/m²) with or without etoposide (1600 mg/m²). Main
toxicity was gastrointestinal. Limiting carboplatin to AUC 20 and eliminating
etoposide resulted in manageable toxicity (69% without grade 3/4 toxicity). One
patient died from treatment-related pneumonitis. At 8 years median follow-up,
median progression-free-survival (PFS) and overall survival (OS) is 13.3 and 37.0
months. Five-years PFS and OS is 18 and 33%. Multicycle HDCT is feasible in a
multicenter setting. A European phase III trial based on this regimen is evaluating
the efficacy of HDCT.
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EM2006335597
Kuzhan O; Arpaci F; Özet A; Öztürk B; Kömürcü S
Titel:
Delayed molgramostim administration after autologous peripheral
blood stem cell transplantation does not add any benefit regarding
hematological engraftment and supportive therapy requirements: A
prospective randomized trial
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27 von 74
Turkish Journal of Cancer; VOL: 36 (2); p. 57-63 /2006/
http://www.turkjcancer.org/pdf/pdf_TJC_426.pdf
EMBASE
English
The administration of hematopoietic growth factors after autologous peripheral
stem cell transplantation is still controversial. In this prospective, randomized trial
we aimed to investigate the impact of GM-CSF after the transplantation with GCSF mobilized peripheral blood stem cells with respect to hematological
engraftment and supportive therapy requirements. Thirty-one patients with solid
and hematological malignancies were randomized in one group (n=16) receiving
GM-CSF (Molgramostim, Leucomax; Sandoz-Schering- Plough Laboratories,
Paris, France) from day 7 post transplant until neutrophil recovery (absolute
neutrophil count >0.5×109/L on three consecutive days) or in
another group (n=15) receiving no GM-CSF. All patients received total CD34+
cells more than 2×106/kg. The patients in both groups were
comparable for age, sex, time between diagnosis and transplantation, total
numbers of pretransplant chemotherapy regimens, previous radiotherapy, tumor
type (solid or hematological) and numbers of total CD34+ cells infused. There
was no difference between cytokine and nocytokine group with respect to
leukocyte engraftment (11.9±2.2 vs. 11.9±2.9 days, respectively; p=0.936),
platelet engraftment (12.6±3.6 vs. 11.9±3.9 days, respectively; p=0.691), number
of days with parenteral antibiotherapy (10.8±4.7 vs. 11.9±3.7 days, respectively;
p=0.662), number of days with fever over 38.1 ° C (6.3±4.3 vs. 5.0±3.0 days,
respectively; p=0.551), the use of red cells (2.6±1.7 vs. 2.9±1.0 units, respectively;
p=0.623), the use of platelet transfusions (1.2±1.0 vs. 1.3±1.0 units, respectively;
p=0.773), duration of posttransplant hospitalization (13.1±2.7 vs. 13.5±2.6 days,
respectively; p=0.435). This randomized trial suggested that the administration of
GM-CSF from day 7 until engraftment after autologous peripheral blood stem cell
transplantation did not add any evident clinical benefit in terms of engraftment
duration and supportive therapy requirements.
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EM2006252164
Eselgrim M; Grunert H; Kühne T; Zoubek A; Kevric M; Bürger H; Jürgens H;
Mayer-Steinacker R; Gosheger G; Bielack SS
Titel:
Dose intensity of chemotherapy for osteosarcoma and outcome in the
Cooperative Osteosarcoma Study Group (COSS) trials
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DOI:
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10.1002/pbc.20608
EMBASE
English
Background. The prognostic relevance of dose intensity in the treatment of
osteosarcoma is still under discussion. The aim of this study was to investigate
whether higher dose intensities of chemotherapy correlated with better outcomes.
Procedure. This study contains 917 consecutive Cooperative Osteosarcoma Study
Group (COSS) patients <40 years with primary, high-grade central, nonmetastatic
osteosarcoma of the extremities, who were in complete remission at least until day
200 after the start of chemotherapy. All COSS-protocols were based on a uniform
treatment concept of aggressive polychemotherapy and definitive surgery.
Chemotherapy dose intensity in the first 200 days of treatment
(DI200) and possible correlations to overall and event-free survival
were investigated. The study focused on methotrexate, doxorubicin, cisplatin, and
ifosfamide, which are considered to be the most active drugs against
osteosarcoma. Multivariate analyses including well-known prognostic factors
were added to complete this investigation. Results. Until day 200, patients
received 80.7 ± 26.1 g/m² methotrexate (MTX); 242 ± 69 mg/m² doxorubicin
(DOX); 324 ± 133 mg/m² cisplatin (DDP); and 13.9 ± 9.8 g/m ² ifosfamide (IFO)
(mean ± SD). Median follow-up from day 200 was 6.6 (0.02-22.1) years. There
was no correlation between a higher DI 200 of any one drug and
better outcomes in uni- or multi-variate analyses. Total treatment intensity did not
show such correlations either. Conclusions. In an overall setting of intensive
multidrug treatment of osteosarcoma, we could not prove that higher dose
intensities correlate with better outcomes. © 2005 Wiley-Liss, Inc.
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EM2005583981
Zaucha RE; Buckner DC; Barnett T; Holmberg LA; Gooley T; Hooper HA;
Maloney DG; Appelbaum F; Bensinger WI
Titel:
Modified total body irradiation as a planned second high-dose
therapy with stem cell infusion for patients with bone-based
malignancies
Source:
International Journal of Radiation Oncology Biology Physics; VOL: 64 (1);
p. 227-234 /20060101/
10.1016/j.ijrobp.2005.06.005
EMBASE
English
Purpose: To estimate the maximum tolerated dose of hyperfractionated total
marrow irradiation (TMI) as a second consolidation after high-dose chemotherapy
with autologous or syngeneic blood stem cell transfusion for patients with
bone/bone marrow-based malignant disease. Patients and Methods: Fifty-seven
patients aged 3-65 years (median, 45 years), including 21 with multiple myeloma,
24 with breast cancer, 10 with sarcoma, and 2 with lymphoma, were treated with
1.5 Gy administered twice daily to a total dose of 12 Gy (n = 27), 13.5 Gy (n =
12), and 15 Gy (n = 18). Median time between the 2 transplants was 105 days
(range, 63-162 days). Results: All patients engrafted neutrophils (median, Day 11;
range, Day 9-23) and became platelet independent (median, Day 9; range, Day 736). There were 5 cases of Grade 3-4 regimen-related pulmonary toxicity, 1 at 12
Gy, and 4 at 15 Gy. Complete responses, partial responses, and stabilizations were
achieved in 33%, 26%, and 41% of patients, respectively. Kaplan-Meier estimates
of 5-year progression-free survival and overall survival for 56 evaluable patients
are 24% and 36%, respectively. Median time of follow-up among survivors was
96 months (range, 77-136 months). Conclusion: Total marrow irradiation as a
second myeloablative therapy is feasible. The estimated maximum tolerated dose
for TMI in a tandem transplant setting was 13.5 Gy. Because 20% of patients are
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surviving at 8 years free of disease, further studies of TMI are warranted. © 2006
Elsevier Inc.
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EM2005411971
Ashihara E; Shimazaki C; Okano A; Hatsuse M; Okamoto A; Shimura K;
Takahashi R; Sumikuma T; Inaba T; Fujita N; Murakami S; Haruyama H;
Nakagawa M
Titel:
Infusion of a high number of CD34+ cells provides a rapid
hematopoietic recovery and cost savings in autologous peripheral
blood stem cell transplantation
Source:
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Japanese Journal of Clinical Oncology; VOL: 32 (4); p. 135-139 /2002/
10.1093/jjco/hyf030
EMBASE
Background: The objectives of this study were to evaluate the effect of the number
of infused CD34+ cells on hematopoietic recovery and on the cost in autologous
peripheral blood stem cell transplantation (PBSCT). Methods: Sixty-nine patients
who received autologous PBSCT (ABSCT) were divided into three groups
defined by the number of infused CD34+ cells. The number of days until 0.5 ×
109/l neutrophils and 50 × 109/l platelets, the number
of transfused blood products, the febrile days, the duration of parenteral antibiotics
and the cost of additional supportive care (transfusions of blood products and
parenteral antibiotics) were analyzed. Results: Twenty-three patients received
<2.5 × 106/kg of CD34+ cells (group A), 25 patients received >=2.5
to 5 × 10 6/kg of CD34+ cells (group B) and 21 patients received
>=5 × 106/kg of CD34+ cells (group C). Patients in group C had
rapid neutrophil (p < 0.01) and platelet (p < 0.05) recovery and required less
platelet transfusions (p < 0.05) than patients in other groups. Transfusions of red
blood cell concentrates, the duration of febrile days or parenteral antibiotics were
not statistically different between the two groups. The patients in group C required
significantly lower costs for platelet concentrates and additional supportive care (p
< 0.05). Conclusion: Infusion of >=5 × 106/kg of CD34+ cells in
ABSCT shortens hematopoietic recovery and reduces costs for additional
supportive care. © 2002 Foundation for Promotion of Cancer Research.
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EM2005391275
Goldstein-Jackson SY; Gosheger G; Delling G; Berdel WE; Exner GU; Jundt G;
Machatschek J-N; Zoubek A; Jürgens H; Bielack SS
Titel:
Extraskeletal osteosarcoma has a favourable prognosis when treated
like conventional osteosarcoma
Source:
Journal of Cancer Research and Clinical Oncology; VOL: 131 (8); p. 520-526
/200508/
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10.1007/s00432-005-0687-7
EMBASE
English
Purpose: The aims of this analysis were to investigate the clinical features of
extraskeletal osteosarcoma (ESOS) and examine the outcome after multi-modal
therapy. Methods: The co-operative osteosarcoma study-group database was
searched for patients with extraskeletal osteosarcoma. Eligible patients were
included in a retrospective analysis of patient, tumour and treatment related
variables and outcome. As for conventional osteosarcoma, scheduled treatment
included surgery and multi-agent chemotherapy. Results: Seventeen eligible
patients were identified with a median age of 44 years (range, 3-65 years). The
thigh was the commonest tumour site. Two patients had a history of previous
malignancies and two had primary metastases. Median follow-up was 3.2 years
(range: 0.6-7.4 years) and at last follow-up, 11 patients were alive in complete
remission, 3 patients were alive with disease and 3 patients had died of their
disease. Three-year overall actuarial and event-free survival rates were 77% and
56%, respectively. Patients with macroscopically complete surgical remission had
an improved overall survival (P=0.0004). Conclusions: The patients in this
retrospective study had a surprisingly good survival rate. This may be due to the
combination of multi-agent chemotherapy with surgery, and we recommend this
approach in the treatment of ESOS. © Springer-Verlag 2005.
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EM2005377855
Arpaci F; Ataergin S; Ozet A; Erler K; Basbozkurt M; Ozcan A; Komurcu S;
Ozturk B; Celasun B; Kilic S; Kuzhan O
Titel:
The feasibility of neoadjuvant high-dose chemotherapy and
autologous peripheral blood stem cell transplantation in patients
with nonmetastatic high grade localized osteosarcoma: Results of a
phase II study
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Cancer; VOL: 104 (5); p. 1058-1065 /20050901/
10.1002/cncr.21279
EMBASE
English
BACKGROUND. The primary and secondary objectives of the current study were
to improve the >= 90% tumor necrosis rate and assess the toxicity profile of the
neoadjuvant high-dose chemotherapy (HDC) regimen, respectively. METHODS.
Twenty-two patients with AJCC Stage IIB high-grade osteosarcoma were
included in the current study. Two cycles of an induction chemotherapy regimen
including cisplatin, doxorubicin, and ifosfamide followed by HDC and autologous
peripheral blood stem cell support or transplantation (APBSCT) were given. After
engraftment was achieved, the patients underwent limb-sparing surgery (LSS)
followed by three to six cycles of postoperative chemotherapy depending on the
tumor necrosis rate. RESULTS. The median follow-up, the total duration of
treatment, and the time to surgery were 23.7 months, 5.96 months, and 3.03
months, respectively. The necrosis rate was at least 90% in 82% of the cases. The
3-year overall survival (OS) and disease-free survival (DFS) rates were 83% and
70%, respectively. Leukopenia, anemia, thrombocytopenia, nausea and emesis,
and mucositis were the most frequent Grade 3 and Grade 4 toxicities (according to
the National Cancer Institute Common Toxicity Criteria [version 2.0]) of
induction, high-dose, and adjuvant chemotherapies. At the time of last follow-up,
no patient had died of chemotherapeutic toxicity. LSS was performed in all
patients. Surgery-related complications were reported in 3 of 22 patients.
Functional scoring results were excellent in eight patients, good in nine patients,
fair in two patients, and poor in three patients. CONCLUSIONS. The results of
the current Phase II study suggest that neoadjuvant HDC provides a greater than
90% necrosis rate with acceptable toxicity. A short duration of therapy and the
feasibility of LSS in all patients are additional advantages of this approach. ©
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EM2005148283
Nieto Y; Shpall EJ; Bearman SI; McSweeney PA; Cagnoni PJ; Matthes S;
Gustafson D; Long M; Barón AE; Jones RB
Titel:
Phase I and pharmacokinetic study of docetaxel combined with
melphalan and carboplatin, with autologous hematopoietic
progenitor cell support, in patients with advanced refractory
malignancies
Source:
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Biology of Blood and Marrow Transplantation; VOL: 11 (4); p. 297-306 /200504/
10.1016/j.bbmt.2005.01.002
EMBASE
English
The purpose of this study was to define the maximal tolerated dose (MTD),
extramedullary toxicities, and pharmacokinetics of docetaxel combined with highdose melphalan and carboplatin with autologous hematopoietic progenitor cell
support. Fifty-nine patients with advanced refractory malignancy (32 breast
cancer, 10 non-Hodgkin lymphoma, 6 germ cell tumors, 4 Hodgkin disease, 4
ovarian cancer, 2 sarcoma, and 1 unknown primary adenocarcinoma) with a
median of 3 prior chemotherapy regimens and a median of 3 organs involved were
enrolled. Treatment included docetaxel (150-550 mg/m² infused over 2 hours on
day -6), melphalan (150-165 mg/m² infused over 15 minutes from day -5 to -3),
and carboplatin (1000-1300 mg/m² as a 72-hour continuous infusion from day -5).
Five patients died from direct regimen-related organ toxicity (2 capillary leak
syndrome, 2 enterocolitis, and 1 hepatic toxicity), and 1 additional patient died
from pulmonary aspergillosis. The docetaxel MTD was defined as 400 mg/m²,
combined with melphalan (150 mg/m²) and carboplatin (1000 mg/m²). The MTD
cohort was expanded to enroll a total of 26 patients, 1 of whom died from toxic
enterocolitis. The remaining 25 patients presented the following extramedullary
toxicity profile, which was manageable and largely reversible: stomatitis,
myoarthralgias, peripheral neuropathy, gastrointestinal and cutaneous toxicities,
and syndrome of inappropriate antidiuretic hormone secretion. Docetaxel
exhibited linear pharmacokinetics in the dose range tested (150-550 mg/m²).
Pharmacodynamic correlations were noted between the docetaxel area under the
curve and peripheral neuropathy or stomatitis. The response rate among 38
patients with measurable disease was 95%, with 47% complete responses. At a
median follow-up of 26 months (range, 7-72 months), the 3-year event-free
survival and overall survival were 26% and 36%, respectively. In conclusion, a 4fold dose escalation of docetaxel, combined with melphalan and carboplatin, is
feasible with autologous hematopoietic progenitor cell support. The notable
activity of this regimen in treatment-refractory patients warrants its further
evaluation. © 2005 American Society for Blood and Marrow Transplantation.
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EM2004505694
Gil A; Portilla AG; Brun EA; Sugarbaker PH
Titel:
Clinical perspective on desmoplastic small round-cell tumor
Source:
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Oncology; VOL: 67 (3-4); p. 231-242 /2004/
10.1159/000081323
EMBASE
English
Rare diseases are often associated with uninformed medical decisions and poorly
executed treatments because of inexperience of the physicians. Desmoplastic
small round-cell tumor is a rare disease that is a form of peritoneal surface
malignancy usually affecting young males, with a mean survival of 29 months. In
order to begin to build a more knowledgeable clinical pathway all 7 patients
treated at the Washington Hospital Center were studied and compared to patients
described in the medical literature. Clinical and pathological data, tumor
distribution, cytoreductive surgery, completeness of cytoreduction and survival
were recorded and analyzed. The first most common symptoms were pain,
increased abdominal girth and palpable abdominal mass in our patients and in the
literature review. The overall survival did not improve with cytoreductive surgery
plus intraperitoneal chemotherapy (mean survival 32 months); however, 2 longterm survivors who responded to systemic chemotherapy of 55 and 101 months
were recorded. The latter may be the longest survivor reported in the literature. No
consistent response to chemotherapy was observed in our patients or in any
literature review. Complete surgical removal of this malignancy did not correlate
with survival in our patients. The absence of improved survival of our
aggressively treated patients as compared to the literature was thought to be a
consequence of an advanced stage of the disease. A new comprehensive approach
that uses complete clearing of cancer by surgery and perioperative systemic and
perioperative intraperitoneal chemotherapy as early as is possible in the natural
history of the disease emerged as goals for future management. Copyright © 2004
S. Karger AG, Basel.
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EM2004437570
Garami M; Schuler D; Babosa M; Borgulya G; Hauser P; Müller J; Paksy A;
Szabó E; Hidvégi M; Fekete G
Titel:
Fermented wheat germ extract reduces chemotherapy-induced
febrile neutropenia in pediatric cancer patients
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Journal of Pediatric Hematology/Oncology; VOL: 26 (10); p. 631-635 /200410/
EMBASE
English
Purpose: An open-label, matched-pair (by diagnosis, stage of disease, age, and
gender) pilot clinical trial was conducted to test whether the combined
administration of the medical nutriment MSC (Avemar) with cytotoxic drugs and
the continued administration of MSC on its own help to reduce the incidence of
treatment-related febrile neutropenia in children with solid cancers compared with
the same treatments without MSC. Methods: Between December 1998 and May
2002, 22 patients (11 pairs) were enrolled in this study. At baseline, the staging of
the tumors was the same in each pair (mostly pTNM = T2N0M0), with the
exception of two cases in which patients in the MSC group had worse prognoses
(metastasis at baseline). There were no significant differences in the average age
of the patients, the length of treatment time (MSC) or follow-up, the number of
patients with central venous catheters, the number of chemotherapy cycles, the
frequency of preventive counterneutropenic interventions, or the type and dosage
of antibiotic and antipyretic therapy used in the two groups. Results: During the
treatment (follow-up) period, there was no progression of the malignant disease,
whereas at end-point the number and frequency of febrile neutropenic events
significantly differed between the two groups: 30 febrile neutropenic episodes
(24.8%) in the MSC group versus 46 (43.4%) in the control group (Wilcoxon
signed rank test, P < 0.05). Conclusions: The continuous supplementation of
anticancer therapies with the medical nutriment MSC helps to reduce the
incidence of treatment-related febrile neutropenia in children with solid cancers.
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EM2004374464
Fiegl M; Schlemmer M; Wendtner C-M; Abdel-Rahman S; Fahn W; Issels RD
Titel:
Ifosfamide, carboplatin and etoposide (ICE) as second-line regimen
alone and in combination with regional hyperthermia is active in
chemo-pre-treated advanced soft tissue sarcoma of adults
Source:
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International Journal of Hyperthermia; VOL: 20 (6); p. 661-670 /200409/
10.1080/02656730410001714959
EMBASE
English
Purpose: To evaluate the efficacy and safety of the combination of ICE
(ifosfamide 1.5g m-2, carboplatin 100mg m-2 and
etoposide 150mg m-2, days 1-4, q 28 days, G-CSF 5 mu g kg1 starting from day 6) alone and in combination with regional hyperthermia
(RHT) in soft tissue sarcoma (STS) refractory to previous standard doxorubicinifosfamide-based chemotherapy. Patients and methods: Twenty patients with
advanced STS of different histological sub-types were treated with the ICE
regimen with 13 patients receiving additional RHT. A median of four courses of
ICE were administered with RHT on days 1 and 3 (60 min, T<inf>max</inf>
42°C). Results: The objective response rate was 20%, with four partial responses
(all treated with hyperthermia). In addition, two patients showed mixed responses
and five patients stable disease. After a median follow-up time of 15 months,
median time to progression was 6 months. Progression free rate estimates were
60% and 45% at 3 and 6 months, respectively. Median overall survival for all
patients was 14.6 months. Conclusion: These results suggest that ICE alone or
combined with RHT shows activity as second-line therapy in doxorubicinifosfamide-refractory STS. © 2004 Taylor & Francis Ltd.
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EM2004352974
Ritchie DS; Grigg AP; Roberts AW; Rosenthal MA; Fox RM; Szer J
Titel:
Staged autologous peripheral blood progenitor cell transplantation
for Ewing sarcoma and rhabdomyosarcoma
Source:
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Internal Medicine Journal; VOL: 34 (7); p. 431-434 /200407/
10.1111/j.1444-0903.2004.00630.x
EMBASE
English
37 von 74
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EM2004184998
Rieger C; Fiegl M; Tischer J; Ostermann H; Schiel X
Titel:
Incidence and severity of ifosfamide-induced encephalopathy
Source:
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Anti-Cancer Drugs; VOL: 15 (4); p. 347-350 /200404/
EMBASE
English
This retrospective trial was performed to determine risk factors, incidence and
severity of ifosfamide-induced encephalopathy in correlation with patient and
treatment characteristics. Patients receiving ifosfamide were included
consecutively with no restrictions concerning disease, prior chemotherapy or
disease stage. Incidence and severity of encephalopathy were graduated according
to common toxicity criteria. Between July 2001 and July 2002, 60 patients (32
male, 28 female, median age 47.5 years) were included; 26.6% of the patients (n =
16) developed neurological symptoms [grade 1: 6.7% (n = 4); grade 2: 3.3% (n =
2); grade 3: 11.7% (n = 7); grade 4: 5% (n = 3)]. Encephalopathy occurred for the
first time in 87.5% (n = 14) in chemotherapy courses 1 and 2. In 56.25% (n = 9) of
these 16 patients only one episode was observed. There was no significant
difference concerning age (38 versus 50 years, p = 0.08) and dosage (median 2.9
versus 2.8 g, p = 0.74) between patients with and without encephalopathy. No risk
factors could be identified by this study, suggesting an individual predisposition in
each patient. On the other hand, ifosfamide can be administered in older patients
without increased risk of neurotoxicity. © 2004 Lippincott Williams & Wilkins.
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EM2003490012
Recchia F; De Fillipis S; Piccinini M; Rea S
Titel:
High-dose Carboplatin, Cyclophosphamide, Etoposide with
Hematological Growth Factors, without Stem Cell Support in
Patients with Advanced Cancer
Source:
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Anticancer Research; VOL: 23 (5 B); p. 4141-4147 /200309/
EMBASE
English
Purpose: Peripheral blood progenitor cell (PBPC) transplantation, introduced into
clinical practice to decrease the hematological toxicity of high-dose chemotherapy
(HDCT), is both a costly procedure and a potential source of tumor cell reinfusion.
The maximum tolerated dose of carboplatin (CB), cyclophosphamide (CT) and
etoposide (VP) administered with growth factors without PBPC was determined in
a previous phase I study. The aim of this phase II study was to evaluate the
activity and toxicity of HDCT with CB, CT and VP administered with growth
factors, without PBPC in a group of patients with advanced solid tumors. Patients
and Methods: Forty patients with a median age of 52 years received two
consecutive courses of chemotherapy every four weeks, consisting of CT 1500
mg/m² VP 400 mg/m² and CB AUC of 7-8. Following chemotherapy,
hematological growth factors were administered for 14 days. Results: Grade 4
leukopenia and thrombocytemia occurred in 40 and 21 patients, respectively. An
overall response rate of 72.5% was achieved. After a median 81 months followup, median time to progression and overall survival were 29 and 38 months,
respectively. Conclusion: These data indicate that HDCT chemotherapy may be
delivered safely without PBPC support. Prolonged responses were observed in
patients that had few therapeutic options.
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EM2003444059
Boccardo F; Guglielmini P
Titel:
Ifosfamide in urologic cancer
Source:
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Oncology; VOL: 65 (SUPPL. 2); p. 67-72 /2003/
10.1159/000073363
EMBASE
English
The therapeutic activity of ifosfamide in urologic tumors has been reviewed.
Ifosfamide has definite activity in nephroblastoma, where it represents the
treatment of choice for children who are not cured by front-line chemotherapy,
and for the adults who are diagnosed with this uncommon disease. Definite
therapeutic activity has also been shown in patients with urothelial tract
malignancies and it represents a major option for patients failing first-line
cisplatin-based chemotherapy. However, promising results have been achieved in
chemo-naïve patients in combination with taxanes or gemcitabine, though at the
price of relevant toxicity. A modest activity has been shown by ifosfamide in renal
cancer (including the sarcomatoid variant) and in hormone-refractory prostate
cancer, which unfortunately respond poorly to cytotoxic chemotherapy. No results
of ifosfamide in penile carcinoma are available so far. Copyright © 2003 S.
Karger AG, Basel.
40 von 74
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Autoren:
EM2003297159
Pakos EE; Ioannidis JPA
Titel:
The association of P-glycoprotein with response to chemotherapy
and clinical outcome in patients with osteosarcoma: A meta-analysis
Source:
DOI:
SU:
Sprache:
AB:
Cancer; VOL: 98 (3); p. 581-589 /20030801/
10.1002/cncr.11546
EMBASE
English
BACKGROUND. There is controversy regarding whether P-glycoprotein (Pgp)
may be a prognostic factor for the response to chemotherapy and clinical disease
progression in patients with osteosarcoma. METHODS. The authors conducted a
meta-analysis of 14 studies (n = 631 patients) that evaluated the correlation
between Pgp and histologic response to chemotherapy and clinical disease
progression (death, metastasis, or recurrence). Data were synthesized in receiver
operating characteristic curves and with fixed-effects and random-effects
likelihood ratios and risk ratios. RESULTS. Pgp had no discriminating ability for
identifying poor responders versus good responders to chemotherapy: The positive
likelihood ratio was 1.15 (95% confidence interval [95% CI], 0.93-1.43), and the
negative likelihood ratio was 0.88 (95% CI, 0.65-1.18; random-effects
calculations). There was some between-study heterogeneity, but no study showed
strong discriminating ability. Conversely, Pgp positivity increased the risk of
disease progression 1.92-fold (95% CI, 1.18-3.13; random-effects calculations)
with some between-study heterogeneity that disappeared when only studies that
employed immunohistochemistry were considered (risk ratio, 2.23; 95% CI, 1.373.64). The results were robust in various sensitivity analyses, although smaller
studies tended to show stronger associations with the risk of disease progression
compared with larger studies (P = 0.03). CONCLUSIONS. The available evidence
showed conclusively that Pgp was not associated with the histologic response of
patients with osteosarcoma to combination chemotherapy regimens. Conversely,
Pgp positivity, as determined by immunohistochemistry, was a strong correlate of
more rapid disease progression, although there was heterogeneity across the
performed studies that, to some extent, may have reflected bias, differential
measurements of Pgp, or confounding with other risk factors. © 2003 American
Cancer Society.
41 von 74
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Autoren:
EM2003229840
Westermann AM; Wiedemann GJ; Jager E; Jager D; Katschinski DM; Knuth A;
Vörde Sive Vörding PZ; Van Dijk JDP; Finet J; Neumann A; Longo W;
Bakhshandeh A; Tiggelaar CL; Gillis W; Bailey H; Peters SO; Robins HI
Titel:
A systemic hyperthermia oncologic working group trial: Ifosfamide,
carboplatin, and etoposide combined with 41.8°C whole-body
hyperthermia for metastatic soft tissue sarcoma
Source:
DOI:
SU:
Sprache:
AB:
Oncology; VOL: 64 (4); p. 312-321 /2003/
10.1159/000070287
EMBASE
English
Background: Based on earlier clinical and preclinical studies, we conducted a
phase II trial in metastatic sarcoma patients of the combination of 41.8°C (x60
min) radiant heat (Aquatherm®) whole-body hyperthermia (WBH) with 'ICE'
chemotherapy. The ICE regimen consists of ifosfamide (5 g/m²), carboplatin (300
mg/m²) and etoposide (100 mg/m²), concurrent with WBH, with etoposide also on
days 2 and 3 post-WBH. Methods: Therapy was delivered every 4 weeks for a
maximum of 4 cycles. All patients received filgrastim or lenograstim. Results: Of
108 patients enrolled as of September 2001, 95 are evaluable for response. Of the
evaluable patients (mean ECOG performance status ~1; mean age 42.3; 58%
male) 33 had no prior therapy for metastatic disease, and 62 were pretreated
(mean: 1.5 prior regimens). The overall response rate was 28.4% (4 complete
remissions and 23 partial remissions) with stable disease (SD) in 31 patients. For
no prior therapy, the response rate was 36%; in pretreated patients it was 24%.
The median overall survival by Kaplan-Meier estimates was 393 days (95% CI
327, 496); the median time to treatment failure was 123 days (95% CI 77, 164).
The major toxicity (287 cycles) was grade 3 or 4 neutropenia and
thrombocytopenia seen in 79.7 and 60.6% of treatments respectively; there were 7
episodes of infection (grade 3/4) with 2 treatment-related deaths, bot involving
disease progression and ureteral obstruction. Conclusion: These results are
consistent with continued clinical investigation of this combined modality
approach. Copyright © 2003 S. Karger AG, Basel.
42 von 74
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Autoren:
EM2003200095
Meyer T; McTiernan A; Whelan J
Titel:
A phase II study of docetaxel in patients with relapsed and
refractory Ewing's tumours
Source:
DOI:
SU:
Sprache:
AB:
Sarcoma; VOL: 7 (1); p. 13-17 /200303/
10.1080/1357714031000114192
EMBASE
English
Purpose. The prognosis for patients with Ewing's tumours who have metastases at
presentation or who are reftactory to standard chemotherapy regimens remains
poor. There is therefore a need to evaluate the role of new agents. This report
describes the initial results of a prospective phase II trial of docetaxel in patients
with progressive or reftactory Ewing's tumours. Patients and methods. Fourteen
patients with Ewing's tumours who had all relapsed or progressed after treatment
with multi-drug cytotoxic therapy were treated with docetaxel 100 mg/m² infused
over 1 h, three weekly for a maximum of six cycles. Nine patients received
granulocyte colony-stimulating factor with all cycles. Results. A partial response
was observed in one patient and stable disease in two. The remaining patients
progressed on treatment. The major toxicity was myelosuppression and infection
with 36% patients experiencing grade 3 or 4 neutropenia and/or infection.
Conclusion. Docetaxel appears to have some activity in Ewing's tumours even in
heavily pre-treated patients. Further evaluation of its efficacy at an earlier stage of
the disease is warranted.
43 von 74
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Autoren:
EM2003017877
Zumberg MS; Leather HL; Nejame C; Meyer C; Wingard JR
Titel:
GM-CSF versus G-CSF: Engraftment characteristics, resource
utilization, and cost following autologous PBSC transplantation
Source:
DOI:
SU:
Sprache:
AB:
Cytotherapy; VOL: 4 (6); p. 531-538 /2002/
10.1080/146532402761624692
EMBASE
English
Background: G-CSF and GM-CSF have both been shown to decrease the time to
hematopoietic recovery when administered after autologous BM or peripheral
stem cell re-infusion. However, few studies have compared G-CSF and GM-CSF
to determine which is the preferred myeloid growth factor. Methods: This study
compares a prospectively accrued cohort of 22 patients receiving GM-CSF with a
historical cohort of patients who received G-CSF commencing Day + 6 after
autologous PBSC transplantation. Patients were matched based on disease type
and stage, CD34+ cell dose/kg, conditioning regimen, and prior
treatment. Time to myeloid engraftment, growth factor utilization, antibiotic
utilization, fever incidence, and cost were compared. Results: The median time to
neutrophil and platelet engraftment was similar in the two groups (ANC > 500 /
mm³, GM-CSF 12 versus G-CSF 11, P = 0.69). There was a trend towards more
days of temperature > 38.0 °C (six versus three, P = 0.05) and febrile neutropenia
(three versus two, P = 0.06) in the GM-CSF arm. There was a trend towards
increased use of i.v. antibiotics in the GM-CSF cohort (7.6 days versus 5.5 days, P
= 0.06). More chest X-rays (1.5 versus 1.0, P = 0.03) were ordered, and more
blood cultures drawn (4.2 versus 2.7, P = 0.05) as part of fever evaluation in the
group treated with GM-CSF. Resource utilization based on actual wholesale
pricing (AWP) favored the G-CSF cohort. Applying a sensitivity analysis, GMCSF became cost-effective when priced below $94 per 250 mu g, despite greater
resource utilization. Discussion: This study suggests that engraftment
characteristics are similar with GM-CSF and G-CSF following PBSC
transplantation. Resource utilization for fever treatment and evaluation may be
greater with GM-CSF. Determination of which agent is more cost-effective
depends on institutional acquisition costs.
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EM2003165549
Autoren:
Matsubara H; Makimoto A; Higa T; Kawamoto H; Takayama J; Ohira M;
Yokoyama R; Beppu Y; Takaue Y
Titel:
Possible benefits of high-dose chemotherapy as intensive
consolidation in patients with high-risk rhabdomyosarcoma who
achieve complete remission with conventional chemotherapy
Source:
SU:
Sprache:
AB:
Pediatric Hematology and Oncology; VOL: 20 (3); p. 201-210 /200304/
EMBASE
English
The authors reviewed their single-center experience with autologous stem cell
transplantation (SCT) in 22 patients with advanced rhabdomyosarcoma.
Pathological subtypes included alveolar (n = 7) and embryonal types (n = 15). The
conditioning regimen primarily consisted of etoposide, carboplatin, and
melphalan. Fourteen, five, and three patients underwent SCT in CR, PR, and PD,
respectively. Eight patients are currently alive without evidence of disease. The
overall survival rete at 5 years was 70% for 14 patients who were in CR at the
time of SCT. This limited experience warrants the examination of SCT in a
prospective study.
45 von 74
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Autoren:
EM2003072315
Newton HB; Slivka MA; Volpi C; Bourekas EC; Christoforidis GA; Baujan MA;
Slone W; Chakeres DW
Titel:
Intra-arterial carboplatin and intravenous etoposide for the
treatment of mtastatic brain tumors
Source:
DOI:
SU:
Sprache:
AB:
Journal of Neuro-Oncology; VOL: 61 (1); p. 35-44 /200301/
10.1023/A:1021218207015
EMBASE
English
Metastatic brain tumors (MBT) are the most frequent complication of systemic
cancer and often respond poorly to treatment. Median survival is only 16-24
weeks after conventional radiation therapy. Regional intra-arterial (IA)
administration of chemotherapy results in increased tumor uptake of drug and may
improve response rates and survival. Twenty-seven patients with MBT who had
received prior irradiation were treated with IA carboplatin (200 mg/m²/d) and
intravenous (IV) etoposide (100 mg/m²/d) for 2 days every 3-4 weeks. Eighteen
patients (67%) had received prior systemic chemotherapy for their primary tumor.
Patients ranged in age from 19 to 68 years (mean 48.1). Thirteen of 24 evaluable
patients had objective responses (54.2%). There were 6 complete responses
(25%), 6 partial responses (25%), 1 minor response (4.2%), 7 stable disease
(32%), and 5 progressive disease (20.8%). Some patients with multifocal tumors
had a mixture of responses. The median time to progression was 16.0 weeks
overall and 30.0 weeks in responders (range 6-118 weeks). Overall median
survival from the time of protocol initiation was 20.0 weeks. In six responders,
death occurred due to systemic illness unrelated to MBT progression. Therapy
was well tolerated, with predominantly hematologic toxicity. Angiographic
complications were rare. Although these are preliminary results, IA carboplatin
and IV etoposide is safe and well tolerated, appears to be active against brain
metastases, and warrants further study.
46 von 74
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Autoren:
EM2003044175
Arpaci F; Dogru T; Ozturk B; Komurcu S; Ozet A; Yilmaz MI; Beyzadeoglu M;
Turan M; Sengul A; Yalcin A
Titel:
Changes in immunological recovery in patients who received posttransplant G-CSF or GM-CSF after autologous peripheral blood
stem cell transplantation (PBSCT)¹
Source:
DOI:
SU:
Sprache:
AB:
Haematologia; VOL: 32 (3); p. 253-264 /2002/
10.1163/15685590260461066
EMBASE
English
In this prospective study, the effects of granulocyte colony-stimulating factor (GCSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on
immunological reconstitution after autologous peripheral blood stem cell
transplantation (PBSCT) were investigated for 6 months. Thirty-five patients
received G-CSF 5 mu g/kg per day and 26 patients received GM-CSF SC 5 mu
g/kg per day from day 1 to leukocyte engraftment (>1000 per mm³). Peripheral
blood samples were obtained on 14, 28, 100, and 180 days after transplantation for
immunological evaluation. CD3+, CD4+, CD8+, CD19+, and CD56+ cells were
analysed by flow cytometry. Immunoglobulin levels (IgG, IgA, and IgM) and
complement levels (C3c and C4) were measured by nephelometry. Both G-CSF
and GM-CSF groups were comparable with respect to age, sex, the period from
diagnosis to transplantation, total nucleated cells infused, the number of CD34+
cells, conditioning regimens (TBI and non-TBI), and post-transplant infection.
CD3+ and CD8+ cells on day 14 following autologous PBSCT + G-CSF were
significantly higher than following autologous PBSCT + GM-CSF (p = 0.008 and
p = 0.021, respectively). The number of CD4 cells and the CD4/CD8 ratio were
not different at several time points between the two groups. CD19+, CD56+ cells
and immunoglobulin levels showed a faster recovery pattern in the autologous
PBSCT + G-CSF group. The effect of G-CSF on immune reconstitution after
autologous PBSCT is more prominent than that of GM-CSF. The possible role of
haematopoietic growth factor on immune recovery and its clinical importance
should be investigated in further studies.
47 von 74
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Autoren:
EM2002345200
Bisogno G; Carli M; Stevens M; Oberlin O; Treuner J; Scarzello G; Colombatti R;
De Zen L; Pinkerton CR
Titel:
Intensive chemotherapy for children and young adults with
metastatic primitive neuroectodermal tumors of the soft tissue
Source:
DOI:
SU:
Sprache:
AB:
48 von 74
10.1038/sj.bmt.1703617
EMBASE
English
The MMT4 study was designed to explore an intensive chemotherapy regimen
(MMT4-89) and the role of high-dose melphalan (MMT4-91) in children with
metastatic soft tissue sarcoma, including extraosseous peripheral neuroectodermal
tumor (PNET). Thirty-one patients with PNET were treated between 1989 and
1995 (11 according to MMT4-89 and 20 according to MMT4-91). Chemotherapy
consisted of four CEVAIE cycles, each including three 3-week courses: CEV
(carboplatin 500 mg/m², epirubicin 150 mg/m², vincristine 1.5 mg/m²), IVA
ifosfamide 9 g/m², actinomycin 1.5 mg/m², vincristine 1.5 mg/m²), IVE
(ifosfamide 9 g/m², etoposide 600 mg/m², vincristine 1.5 mg/m²). In MMT4-91 the
fourth CEVAIE was replaced with melphalan 200 mg/m² with stem cell rescue.
The CEV combination was evaluated as a window study. Surgery followed the
second cycle. Radiotherapy was administered to post-surgical residual disease.
The response rate was 55% after CEV, rising to 80% after the first CEVAIE.
Twenty-five patients achieved complete remission (CR). Overall, the 5-year EFS
was 22.6%: 36.4% and 15% for patients treated according to MMT4-89 and
MMT4-91, respectively (P = 0.3). Local control was achieved in 77% of irradiated
patients vs 45% of non-irradiated. Age >10 years was associated with significantly
poorer outcome (P = 0.04). In conclusion, despite the high CR rate, intensive
chemotherapy with or without high-dose melphalan appeared to have little impact
on the survival of patients with metastatic extraosseus PNET.
ND:
Autoren:
EM2002066756
Atra A; Pinkerton R
Titel:
High-dose chemotherapy in soft tissue sarcoma in children
Source:
DOI:
SU:
Sprache:
AB:
Critical Reviews in Oncology/Hematology; VOL: 41 (2); p. 191-196 /2002/
10.1016/S1040-8428(01)00155-X
EMBASE
English
Soft tissue sarcomas (STS) are highly malignant tumours that constitute 5-6% of
all malignant childhood neoplasms. Of these, rhabdomyosarcoma (RMS) is the
most common in children, and has a characteristic two-peak age incidence, 2-5
and 15-19 years. Most children with RMS are cured with conventional
chemotherapy and local therapy (surgery with or without radiotherapy). Children
with metastatic disease at presentation, particularly those older than 10 years or
with bone marrow or bone involvement have a much poorer outcome. In this
subgroup, high-dose therapy with stem cell rescue has been studied over the last
two decades. Various single or multiagent chemotherapy regimens with or without
radiotherapy and autologous stem cell rescue have been used as consolidation
treatment with little success. Recent trials using sequential high-dose
chemotherapy in the early phase of treatment have proved to be feasible, but the
beneficial effect has to be confirmed. The role of purging remains unclear.
Collaboration between different international groups is urgently required, in an
attempt to improve the poor outcome of children with high risk STS. Copyright ©
2002 Elsevier Science Ireland Ltd.
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EM2001399650
Ferrari A; Casanova M; Bisogno G; Mattke A; Meazza C; Gronchi A; Ceccheto
G; Fidani P; Kunz D; Treuner J; Carli M
Titel:
Hemangiopericytoma in pediatric ages: A report from the Italian
and German Soft Tissue Sarcoma Cooperative Group
Source:
DOI:
SU:
Sprache:
AB:
Cancer; VOL: 92 (10); p. 2692-2698 /20011115/
10.1002/1097-0142(20011115)92:10<2692::AID-CNCR1623>3.0.CO;2-Y
EMBASE
English
BACKGROUND. Hemangiopericytoma (HPC) is very uncommon in childhood
and comprises two different clinical entities, the adult type and the infantile type,
occurring in the first year of age. We report on a series of 27 pediatric patients
treated from 1978 to 1999 by the Italian and German Soft Tissue Sarcoma
Cooperative Group. METHODS. Seven patients had infantile HPC; complete
resection was achieved in the tumors of five patients and chemotherapy was given
to four patients. Twenty children had adult type HPC; nine received complete
tumor resection (four patients at diagnosis and five at delayed surgery). Postoperative radiotherapy was administered to 15 patients, chemotherapy to 19.
RESULTS. Six of seven patients with infantile HPC were alive in first remission;
one patient died of disease. Chemotherapy achieved an objective response in four
of four patients. Among the adult type HPC cases, 5-year event free survival was
64% (median follow-up 125 months); 12 patients were alive in first remission,
eight patients relapsed and died of disease. Seven of 10 evaluable patients showed
good response to chemotherapy. Statistically significant differences in outcome
were observed in relation to Intergroup Rhabdomyosarcoma Study grouping, size,
local invasiveness, and gender. CONCLUSIONS. Infantile HPC is a unique entity
probably related to infantile myofibroblastic lesions and characterized by a high
response to chemotherapy, which is required in case of unresectable, lifethreatening tumors. In children over 1 year of age, HPC behaves like its adult
counterpart; complete surgical resection remains the mainstay of treatment, but
chemotherapy and radiotherapy seem effective and are recommended in all
patients with incomplete tumor resection and/or locally invasive, large tumors. ©
50 von 74
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Autoren:
EM2001369646
Kushner BH; Cheung N-KV; Kramer K; Dunkel IJ; Calleja E; Boulad F
Titel:
Topotecan combined with myeloablative does of thiotepa and
carboplatin for neuroblastoma, brain tumors, and other poor-risk
solid tumors in children and young adults
Source:
DOI:
SU:
Sprache:
AB:
51 von 74
10.1038/sj.bmt.1703213
EMBASE
English
Topotecan appears to be relatively unaffected by the most common multidrug
resistance mechanisms, may potentiate cytotoxicity of alkylators, has good
penetration into the central nervous system, is active against a variety of
neoplasms, and has myelosuppression as its paramount toxicity. We present our
experience with a myeloablative regimen that includes topotecan. Twenty-one
patients with poor-prognosis tumors and intact function of key organs received
topotecan 2 mg/m² by 30-min intravenous (i.v.) infusion on days -8, -7, -6, -5, -4;
thiotepa 300 mg/m² by 3 h i.v. infusion on days -8, -7, -6; and carboplatin by 4 h
i.v. infusion on days -5, -4, -3 with a daily dose derived from the pediatric Calvert
formula, using a targeted area under the curve of seven mg/ml* min (~500
mg/m²/day). Stem cell rescue was on day 0. The patients were 1 to 29 (median 4)
years old; 18 were in complete remission (CR) and three in partial remission (PR).
Early toxicities were severe mucositis and erythema with superficial peeling in all
patients and a seizure, hypertension, and renal insufficiency followed by venoocclusive disease in one patient each. Post-transplant treatment included
radiotherapy alone (four patients) or plus biological agents (11 patients with
neuroblastoma). With a follow-up of 6+ to 32+ (median 11+) months, event-free
survivors include 10/11 neuroblastoma patients (first CR), 4/5 brain tumor patients
(second PR or CR), 1/3 patients with metastatic Ewing's sarcoma (first or second
CR), and a patient transplanted for multiply recurrent immature ovarian teratoma;
a patient with desmoplastic small round-cell tumor (second PR) had progressive
disease at 8 months. Favorable results for disease control, manageable toxicity,
and the antitumor profiles of topotecan, thiotepa, and carboplatin, support use of
this three-drug regimen in the treatment of neuroblastoma and brain tumors;
applicability to other tumors is still uncertain.
ND:
Autoren:
EM2001067453
Hartmann JT; Vangerow Avon; Fels LM; Knop S; Stolte H; Kanz L; Bokemeyer
C
Titel:
A randomized trial of amifostine in patients with high-dose VIC
chemotherapy plus autologous blood stem cell transplanation
Source:
DOI:
SU:
Sprache:
AB:
British Journal of Cancer; VOL: 84 (3); p. 313-320 /2001/
10.1054/bjoc.2000.1611
EMBASE
English
This pilot study evaluates the degree of side effects during high-dose
chemotherapy (HD-VIC) plus autologous bone marrow transplant (HDCT) and its
possible prevention by the cytoprotective thiol-derivate amifostine. Additionally,
the in-patient medical costs of both treatment arms were compared. 40 patients
with solid tumours were randomized to receive HD-VIC chemotherapy with or
without amifostine (910 mg/m² at day 1-3) given as a short infusion prior to
carboplatin and ifosfamide. Patients were stratified according to pretreatment.
HDCT consisted of an 18 h infusion of carboplatin (500 mg/m²/d over 18 h),
ifosfamide (4 g/m²/d over 4 h) and etoposide (500 mg/m²/d) all given for 3
consecutive days. All patients received prophylactic application of G-CSF (5 pg
mu g-1 subcutaneously) to ameliorate neutropenia after treatment.
Patients were monitored for nephrotoxicity, gastrointestinal side effects,
haematopoietic recovery, as well as frequency of fever and infections. The median
fall of the glomerular filtration rate (GFR) was 10% from baseline in the
amifostine group (105 to 95 ml min-1) and 37% in the control patient
group (107 to 67 ml min-1) (P < 0.01). Amifostine-treated patients
revealed a less pronounced increase in albumine and low molecular weight protein
urinary excretion. Stomatitis grade III/IV occurred in 25% without versus 0% of
patients with amifostine (P = 0.01). Acute nausea/vomiting was frequently
observed immediately during or after the application of amifostine despite
intensive antiemetic prophylaxis consisting of 5-HT<inf>3</inf>-receptor
antagonists/dexamethasone/trifluorpromazine. However, delayed emesis occurred
more often in the control patients. Engraftment of neutrophil (> 500 mu l1) and thrombocytes (> 25 000 mu l-1) were observed at days
9 versus 10 and 10 versus 12, respectively, both slightly in favour of the
amifostine arm. In addition, a lower number of days with fever and a shortened
duration of hospital stay were observed in the amifostine arm. The reduction of
acute toxicity observed in the amifostine arm resulted in 30% savings in costs for
supportive care (Euro 4396 versus Euro 3153 per patient). Taking into account the
drug costs of amifostine, calculation of in-patient treatment costs from the start of
chemotherapy to discharge revealed additional costs of Euro 540 per patient in the
amifostine arm. This randomized pilot study indicates that both organ and
haematotoxicity of HD-VIC chemotherapy can be ameliorated by the use of
amifostine. Additionally, a nearly complete preservation of GFR was observed in
amifostine-treated patients which may be advantageous if repetitive cycles of
HDCT are planned. Larger randomized trials evaluating amifostine cytoprotection
during high-dose chemotherapy are warranted. © 2001 Cancer Research
Campaign.
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Autoren:
EM2000261377
Merimsky O; Meller I; Kollender Y; Issakov J; Flusser G; Inbar M
Titel:
Gemcitabine in bone sarcoma resistant to doxorubicin-based
chemotherapy
Source:
SU:
Sprache:
AB:
Sarcoma; VOL: 4 (1-2); p. 7-10 /2000/
EMBASE
English
Subjects and Methods: Seven patients with progressive localized or metastatic
chemo-resistant osteosarcoma were treated by gemcitabine. The protocol included
gemcitabine 1000 mg/m2/w for 7 consecutive weeks, followed by 1 week rest. If
no progression was observed, maintenance by gemcitabine 1000 mg/m2/w for 3
weeks every 28 days was given until failure was clinically or radiologically
evident. Results. The true objective response rate was 0%. However, disease
stabilization and clinical benefit response were observed in five patients (70%) for
13-96 weeks. Discussion. Postponing the inevitable death with a relatively nontoxic treatment, is, in our opinion, an important issue especially in young patients.
Thus it may be justified and warranted to investigate the activity of gemcitabine in
a larger group of patients with bone sarcomas.
53 von 74
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Autoren:
EM2000104785
Figuerres E; Haut PR; Olzewski M; Kletzel M
Titel:
Analysis of parameters affecting engraftment in children undergoing
autologous peripheral blood stem cell transplants
Source:
SU:
Sprache:
AB:
EMBASE
English
Eighty-three pediatric patients underwent autologous peripheral blood stem cell
transplants at a single institution and were included in a study evaluating the
correlations between five engraftment parameters and the time to both neutrophil
and platelet recovery. The parameters included: the number of nucleated cells per
kg (TNC/kg), the absolute CD34+ cell content per kg
(CD34+/kg), the number of mononuclear cells per kg (MNC/kg), the
number of BFU-E/kg, and the number of CFU-GM/kg. A two-tailed MannWhitney test ( alpha = 0.05) was used to determine if there were significant
differences between patients with neuroblastoma (n = 45) and patients with other
diagnoses (n = 38). No statistically significant differences existed between
neuroblastoma patients and patients with other diagnoses. Therefore, the two
groups of patients were pooled together. Data were analyzed using both a
univariate and multivariate correlation method and Student's t-test ( alpha = 0.05).
Two statistically significant logarithmic relationships were found. The first
relationship was between MNC/kg and time to ANC reconstitution (P = 0.05). The
second relationship was between CFU-GM/kg and time to platelet recovery (P =
0.01). Based on the statistical data, we conclude that there is no correlation
between nucleated cell dose, CD34+ cell dose, and BFU-E content
with either neutrophil or platelet recovery. Accordingly, in this study MNC cell
dose per kilogram was the most important parameter predicting the length of time
between graft infusion and neutrophil recovery while CFU-GM content per
kilogram was the most important parameter predicting the length of time until
platelet recovery.
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Autoren:
EM2000007634
Sola C; Maroto P; Salazar R; Mesia R; Mendoza L; Brunet J; Lopez-Pousa A;
Tabernero JM; Montesinos J; Pericay C; Martinez C; Cancelas JA; Lopez-Lopez
JJ
Titel:
Prognostic factors of peripheral blood stem cell mobilization with
cyclophosphamide and Filgrastim (r-metHuG-CSF): The
CD34+ cell dose positively affects the time to
hematopoietic recovery and supportive requirements after high-dose
chemotherapy
Source:
SU:
Sprache:
AB:
55 von 74
Hematology; VOL: 4 (3); p. 195-209 /1999/
EMBASE
English
To prospectively analyze factors that influence peripheral blood stem cell (PBSC)
collection and hematopoietic recovery after high-dose chemotherapy (HDC), 39
patients received cyclophosphamide 4 g/m² and rHuG-CSF (Filgrastim) 5 mu
g/kg/day. Leukapheresis was started when CD34+ cells/mL were > 5
x 10³. A minimum of 2 x 106 CD34+ cells/kg was
collected. Median steady-state bone marrow CD34+ cell percentage
was 0.8% (range, 0.1 to 6). Thirty-two patients received HDC with autologous
PBSC transplantation plus Filgrastim. A median of 2 (range, 0 to 6) leukapheresis
per patient were performed and a median of 6.3 X 106
CD34+ cells/kg (range, 0 to 44.4) collected; four patients failed to
mobilize CD34+ cells. The number of cycles of prior chemotherapy
had an inverse correlation with the number CD34+ cells/kg collected
(r = -0.38; p < 0.005). Patients with < 7 cycles had a higher predictability for onset
of leukapheresis than patients with ³7 (93% versus 50%; p < 0.005). The four
patients who failed to mobilize had received >= 7 cycles. The number of
CD34+ cells/kg infused after HDC had an inverse correlation with
days to recovery to 0.5 x 109 neutrophils/L and 20 x
109 platelets/L (r = -0.68 and -0.56; p < 0.005). The effect of these
factors on mobilization and hematopoietic recovery were confirmed by
multivariate analysis. Requirements for supportive measures were significantly
lower in patients given a higher dose of CD34+ cells/kg. Therefore,
PBSC collection should be planned early in the course of chemotherapy. Larger
number of CD34+ cells/kg determined a more rapid hematopoietic
recovery and a decrease of required supportive measures.
ND:
Autoren:
EM1999309177
Carli M; Colombatti R; Oberlin O; Stevens M; Masiero L; Frascella E;
Koscielniak E; Treuner J; Pinkerton CR
Titel:
High-dose melphalan with autologous stem-cell rescue in metastatic
rhabdomyosarcoma
Source:
SU:
Sprache:
AB:
Journal of Clinical Oncology; VOL: 17 (9); p. 2796-2803 /199909/
EMBASE
English
Purpose: The European Collaborative MMT4-91 trial was conducted as a
prospective nonrandomized study to evaluate the potential benefit of high- dose
melphalan as consolidation of first complete remission in children with stage IV
rhabdomyosarcoma. Patients and Methods: Fifty-two patients in complete
remission after six courses of chemotherapy received 'megatherapy': 42 received
melphalan alone, whereas 10 received melphalan in combination with etoposide,
carboplatin/etoposide, or thiotepa/busulfan and etoposide. The outcome of this
group of patients was compared with that observed in 44 patients who were also in
complete remission after six courses of identical chemotherapy (plus surgery or
radiotherapy) but went on to receive a total of up to 12 courses of conventional
chemotherapy (four cycles). No differences were found between the two groups
regarding clinical characteristics, chemotherapy received before complete
remission, or response to chemotherapy. In particular, there was no significant
difference between the groups for site of primary tumor, histologic subtype, age at
presentation, presence of bone or bone marrow metastases, or number of
metastases. Results: The 3-year event-free survival (EFS) and overall survival
(OS) rates were 29.7% and 40%, respectively, for those receiving high-dose
melphalan or other multiagent high-dose regimens and 19.2% and 27.7%,
respectively, for those receiving standard chemotherapy. The difference was not
statistically significant (P = .3 and P = .2 for EFS and OS, respectively). There
was a significant prolongation in the time from the last day of high-dose
chemotherapy or the end of chemotherapy cycle 4 to the time of relapse in those
receiving megatherapy (168 days for patients receiving megatherapy v 104 days
for those receiving standard therapy; P = .05). Conclusion: The addition of a highdose alkylating agent to consolidation therapy may have prolonged progressionfree survival in this poor-risk patient group, but it did not significantly improve
the ultimate outcome.
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Autoren:
EM1998077104
Ozkaynak MF; Matthay K; Cairo M; Harris RE; Feig S; Reynolds CP; Buckley J;
Villablanca JG; Seeger RC
Titel:
Double-alkylator non-total-body irradiation regimen with
autologous hematopoietic stem-cell transplantation in pediatric solid
tumors
Source:
SU:
Sprache:
AB:
EMBASE
English
Purpose: To determine the maximum-tolerated dose (MTD) of cyclophosphamide
(CTX) when administered with fixed doses of carboplatin, etoposide, and
melphalan (CEM) followed by autologous hematopoietic stem- cell
transplantation (HSCT) in children with recurrent or high-risk solid tumors as a
consolidation chemotherapy, and to make preliminary observations on efficacy.
Patients and Methods: Twenty-seven patients with solid tumors between the ages
of 2 and 21 years were enrolled. Twenty of 27 had recurrent disease, whereas
seven were treated in first remission. Nine were treated with melphalan 50
mg/m²/d for 4 days, carboplatin 300 mg/m²/d for 4 days as a continuous infusion
(CI), and etoposide 200 mg/m²/d for 4 days as a CI (level I). CTX 750 mg/m²/d for
4 days was added to this regimen for the next 18 patients (level II). Seven of nine
patients at level I and four of 18 at level II received bone marrow (BM) only,
while two of nine at level I and 14 of 18 at level II received BM plus peripheralblood stem cells (PBSC). Results: The median time to reach on absolute
neutrophil count (ANC) greater than 500/ mu L was 12.5 and 10 days for patients
who received BM only and BM plus PBSC, respectively. Three cases of grade 3
mucositis, one Candida sepsis, and two transient hypoxemias were the main
nonfatal toxicities. No toxic mortality was observed among level I patients. Three
of 18 (16%) level II patients, all in second CR, died of transplant-related
complications. Median follow-up is 29 months. Nine died of progressive disease
(one second malignancy), six relapsed and are alive with disease, and nine are in
continuous CR. Among the 15 PNET/Ewing's sarcoma patients, seven are in
continuous CR (three of nine in second CR/VGPR, four of six in first CR/VGPR).
Conclusion: The addition of CTX 3 g/m² to CEM followed by autologous HSCT
as a consolidation therapy resulted in 16% toxic mortality in children with
recurrent or high-risk solid tumors. Further CTX dose escalation was aborted. No
common nonhematologic toxicity was identified. The event-free survival (EFS) of
66% ± 19% at 3 years for patients with metastatic PNET/Ewing's sarcoma in first
remission is encouraging. However, this is based on only six patients. Both level I
and II need further exploration in high-risk pediatric solid tumors in first
remission.
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Autoren:
EM1998066692
Furman WL; Rodman JH; Tonda ME; Luo X; Arnold B; Marina N; Garrison L;
Hanna R; Pratt CB; Meyer WH
Titel:
Clinical effects and pharmacokinetics of the fusion protein PIXY321
in children receiving myelosuppressive chemotherapy
Source:
DOI:
SU:
Sprache:
AB:
10.1007/s002800050733
EMBASE
English
A hemopoietin with the ability to accelerate both platelet and granulocyte
recovery after intensive chemotherapy would have great clinical utility. The
recombinant fusion protein composed of human granulocyte- macrophage colonystimulating factor and interleukin-3 (PIXY321), showed some promise in early
adult trials. However, studies for pediatric patients are limited, and there are no
systematic data on the pharmacokinetics of PIXY321 given over prolonged
periods at current dosage levels. Purpose: To determine the safety, clinical effects
and plasma concentrations of increasing doses of PIXY321 in children treated
with myelosuppressive chemotherapy. Methods: A total of 39 children with
relapsed or high-risk solid tumors were enrolled in this phase I/II study. PIXY321
was administered once or twice daily by subcutaneous injection in total doses of
500 to 1000 mu g/m² per day for 14 days after each course of chemotherapy with
ifosfamide, carboplatin, and etoposide (ICE). Pharmacokinetic studies were
performed on day 1 of the first course in 33 patients and repeated on day 14 in 13
patients (once-daily schedule only). Results: Although mild local skin reactions
and fever were frequent, no dose-limiting toxicity was identified at the maximum
dose studied (1000 mu g/m² per day). There were no statistically significant
differences in chemotherapy-induced hematologic toxicity with increasing doses
of PIXY321 or with twice-daily vs once-daily dosing. On day 1, the median
PIXY321 clearance was 657 ml/min per m² (range 77-1804 ml/min per m²) and
the median half-life was 3.7 h (range 2.1-20.8 h). On day 14, clearance increased
in all patients studied (median increase 63%), with a corresponding decrease in the
median 12-h concentration (from 1.2 to 0.25 ng/ml). Maximum concentrations
were <1 ng/ml in 81% of patients, and only two patients had maximum plasma
concentrations equivalent to those required for consistent activity in vitro.
Conclusions: The recombinant fusion protein PIXY321 proved safe in children
treated with myelosuppressive ICE chemotherapy but had no demonstrable
clinical benefits. The pharmacokinetic studies suggest that the observed lack of
hematologic benefit may be explained by low plasma concentrations resulting
from increased clearance with prolonged administration. Moreover, the significant
increase in PIXY321 systemic clearance in the absence of increased circulating
myeloid cells suggests that the upregulation of either extravascular compartment
hematopoietic progenitor cells or nonhematopoietic cells may play an important
role in controlling circulating concentrations of this unique cytokine. These
findings highlight the importance of a thorough assessment of the systemic
disposition of cytokines when determining the dose and schedule necessary to
achieve clinical activity in patients.
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Autoren:
EM1998055922
Charuruks N; Voravud N; Sriuranpong V
Titel:
MPXI and early neutrophilia: New potential therapeutic biomarkers
for recombinant human granulocyte colony-stimulating factor
Source:
DOI:
SU:
Sprache:
AB:
Journal of Clinical Laboratory Analysis; VOL: 12 (1); p. 41-46 /1998/
10.1002/(SICI)1098-2825(1998)12:1<41::AID-JCLA7>3.0.CO;2-M
EMBASE
English
We evaluated the effect of recombinant human granulocyte colony- stimulating
factor (rhG-CSF) given after myelosuppressive chemotherapy in 15 cancer
patients. No severe neutropenia (absolute neutrophil count, ANC < 0.5 x 10³/ mu
L) was noticed in 10 rhG-CSF primary prophylactic patients, but was noticed in
two of five rhG-CSF secondary prophylactic patients. Neutrophilia characterized
by shift to the left occurred within 24 hours after starting rhG-CSF prophylaxis.
Thereafter, conversion to normal level occurred within 24 hours. The peak of
neutrophilia occurred earlier in the primary group than in the secondary
prophylactic group. The detection of myeloperoxidase (MPO) using flow
cytochemistry blood autoanalyzer (Technicon(R) H*1) was evaluated as mean
peroxidase index (MPXI). Leukocyte alkaline phosphatase (LAP) using the
method of Kaplow (Am J Clin Pathol 39:439-449, 1963) was recorded as LAP
score. There was a statistically significant elevation of MPXI in the primary group
over the secondary prophylactic patients. The LAP activity was in normal range.
There was a slightly decreased red blood cell (RBC) count, hemoglobin (Hb), and
platelet count. In conclusion, rhG-CSF induced neutrophilia with efficient
enzymatic activity. These findings demonstrate the value of rhG-CSF in patients
receiving chemotherapy. MPXI and early neutrophilia may serve as a potential
biomarker of therapeutic efficacy of rhG-CSF.
59 von 74
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Autoren:
EM1997322845
Bramwell VHC
Titel:
The role of chemotherapy in the management of non-metastatic
operable extremity osteosarcoma
Source:
SU:
Sprache:
AB:
Seminars in Oncology; VOL: 24 (5); p. 561-571 /1997/
EMBASE
English
Original articles published between 1991-1996 were selected according to
specified criteria, and reviewed to provide answers to nine important questions
about the role of chemotherapy in the management of nonmetastatic extremity
osteosarcoma: (1) Does adjuvant chemotherapy improve survival? (2) Are the
results of the Rosen T10 protocol reproducible in different settings? (3) Is
chemotherapy with two of the most active drugs (DOX/DDP) an effective
adjuvant treatment, and comparable to other multiagent regimens? (4) Does
histological response to neoadjuvant chemotherapy correlate with reduced local
recurrence and/or improved survival? (5) Does a change of chemotherapy for
patients whose tumors show a poor histological response to chemotherapy
improve survival? (6) Does chemotherapy given before surgery (neoadjuvant)
improve survival? (7) Are certain drugs, or their method of administration (route,
duration, total dose, dose intensity, pharmacokinetics) important in determining
outcomes? (8) Can new agents such as Ifosfamide be incorporated into intensive
multi-agent chemotherapy, and does this improve pathological response and/or
survival? (9) Can dose intensity of treatment be increased with G-CSF? The brief
answers to questions 1-3 and 7-9 are 'Yes'; question 4 'Yes, but may be changing';
and questions 5, 6 'Not proven,' and these are expanded in the text. Future
directions for treatment of osteosarcoma are covered under the headings
identification of new agents, dose intensification, circumvention of drug
resistance, immunotherapy, and insulin-like growth factor.
60 von 74
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Autoren:
EM1997148951
Graham ML; Herndon II JE; Casey JR; Chaffee S; Ciocci GH; Krischer JP;
Kurtzberg J; Laughlin MJ; Lonqee DC; Olson JF; Paleologus N; Pennington CN;
Friedman HS
Titel:
High-dose chemotherapy with autologous stem-cell rescue in patients
with recurrent and high-risk pediatric brain tumors
Source:
SU:
Sprache:
AB:
EMBASE
English
Purpose: We treated 49 patients with recurrent or poor-prognosis CNS
malignancies with high-dose chemotherapy regimens followed by autologous
marrow rescue with or without peripheral-blood stem-cell augmentation to
determine the toxicity of and event-free survival after these regimens. Patients and
Methods: Nineteen patients had medulloblastomas, 12 had glial tumors, seven had
pineoblastomas, five had ependymomas, three had primitive neuroectodermal
tumors, two had germ cell tumors, and one had fibrosarcoma. Thirty-seven
received chemotherapy with cyclophosphamide 1.5 g/m² daily x 4 and melphalan
25 to 60 mg/m² daily x 3. Nine received busulfan 37.5 mg/m² every 6 hours x 16
and melphalan 180 mg/m² (n = 7) or 140 mg/m² (n = 2). Three received
carboplatin 700 mg/m²/d on days -7, -5, and -3 and etoposide 500 mg/m²/d on
days -6, -4, and -2. All patients received standard supportive care. Results:
Eighteen of 49 patients survive event-free 22+ to 55+ months (median, 33+) after
transplantation, including nine of 16 treated before recurrence and nine of 33
treated after recurrence. There was one transplant related death from pulmonary
aspergillosis. Of five patients assessable for disease response, one had a partial
remission (2 months), one has had stable disease (55+ months), and three showed
progression 2, 5, and 8 months after transplantation. Conclusion: The toxicity of
these regimens was tolerable. Certain patients with high-risk CNS malignancies
may benefit from such a treatment approach. Subsequent trials should attempt to
determine which patients are most likely to benefit from high-dose chemotherapy
with autologous stem-cell rescue.
61 von 74
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Autoren:
EM1997127845
Weaver CH; Schwartzberg LS; Hainsworth J; Greco FA; Li W; Buckner CD;
West WH
Titel:
Treatment-related mortality in 1000 consecutive patients receiving
high-dose chemotherapy and peripheral blood progenitor cell
transplantation in community cancer centers
Source:
SU:
Sprache:
AB:
EMBASE
English
High-dose chemotherapy (HDC) with autologous peripheral blood progenitor cell
(PBPC) is being increasingly utilized as a therapeutic modality for patients with
chemotherapy-sensitive disease. Several published HDC regimens have become
relatively widely used. The purpose of this analysis was to determine treatmentrelated mortality (TRM) following administration of five different HDC regimens
in community cancer centers. A retrospective evaluation of 1000 consecutive
patients with leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple
myeloma, sarcoma, ovarian cancer, or breast cancer who received one of five
published HDC regimens followed by PBPC infusion over a 5-year period in
community cancer centers was performed to determine TRM. Fifty-nine patients
(5.9%) died within 100 days of PBPC infusion. Twenty-five patients (2.5%) died
predominantly of causes related to disease progression. Thirty-four patients
(3.4%) died of TRM, 15 patients (1.5%) died from infection and 19 (1.9%) died
from regimen-related toxicities (RRT). In a logistic model, increasing age (P =
0.001) and lower numbers of CD34+ cells/kg (P = 0.003) were
associated with an increased risk of 100-day TRM. High-dose cyclophosphamide,
thiotepa, and carboplatin was associated with a lower risk of mortality than other
regimens (P = 0.0001). High-dose chemotherapy and autologous PBPC support
can be performed in community cancer centers with relative safety. Patient age,
the type of preparative regimen and the number of CD34+ cells
infused were important determinates of mortality.
62 von 74
ND:
Autoren:
EM1997120938
Hartmann O; Le Corroller AG; Blaise D; Michon J; Philip I; Norol F; Janvier M;
Pico JL; Baranzelli MC; Rubie H; Coze C; Pinna A; Méresse V; Benhamou E
Titel:
Peripheral blood stem cell and bone marrow transplantation for
solid tumors and lymphomas: Hematologic recovery and costs: A
randomized, controlled trial
Source:
SU:
Sprache:
AB:
Annals of Internal Medicine; VOL: 126 (8); p. 600-607 /19970415/
EMBASE
English
Background: Previous studies have suggested that peripheral blood stem cell
(PBSC) transplantation has an advantage over autologous bone marrow
transplantation. Objective: To compare the hematologic recovery and costs
associated with PBSC transplantation with those associated with autologous bone
marrow transplantation in patients receiving high-dose chemotherapy for solid
tumors or lymphomas. Design: Multicenter, randomized, controlled clinical trial.
Setting: French Federation of Cancer Centers, located in cancer facilities or public
hospitals with transplantation units. Patients: Children and adults with solid
tumors or lymphomas who were candidates for high-dose chemotherapy.
Interventions: Bone marrow or filgrastim-mobilized PBSCs. Measurement: The
major end point was the duration of thrombocytopenia (platelet count < 50 x
109/L). An economic evaluation of both types of transplantation was
done prospectively to measure costs and cost- effectiveness. Results: 129 patients
entered the trial; 64 had PBSC transplantation, and 65 had bone marrow
transplantation. The median duration of thrombocytopenia was 16 days in the
PBSC group and 35 days in the bone marrow group (P < 0.001). All of the other
clinical end points studied (time to last platelet transfusion, duration of
granulocytopenia, number of transfusion episodes, and duration of hospitalization)
favored PBSC transplantation. A cost analysis showed that total cost was
decreased by 17% in adults and 29% in children with PBSC transplantation; thus,
PBSC transplantation was clearly more cost-effective than bone marrow
transplantation for both platelet and granulocyte recovery. Conclusion:
Transplantation of PBSCs is associated with more rapid hematologic recovery
than is bone marrow transplantation after high-dose chemotherapy for solid
tumors or lymphomas. Furthermore, global costs are lower and cost- effectiveness
ratios are better with PBSC transplantation.
63 von 74
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Autoren:
EM1997064875
Riepl M; Fietkau R; Sauer R
Titel:
G-CSF bei Radiochemotherapie
G-CSF in radiochemotherapy
Source:
Strahlentherapie und Onkologie; VOL: 173 (2); p. 76-82 /199702/
SU:
Sprache:
AB:
64 von 74
EMBASE
German
Background: G-CSF enhances the division, maturation and release of granulocyte
precursor cells. The shortening of chemotherapy-induced leukopenia via G-CSF is
well documented in literature, with fractionated radiotherapy alone one finds a
distinct increase of the granulocyte level. There are only few results for combined
simultaneous radiochemotherapy. Patients and methods: In the Department of
Radiotherapy of the University of Erlangen 102 patients were treated with G-CSF
since 1992. Twenty-eight patients (31 applications) undergoing radiotherapy only
(n = 4) or combined simultaneous radiochemotherapy (n = 27) received G-CSF
interventional daily. These results are presented and discussed. Indications for the
application of G-CSF were severe leukopenia below 1000/mm³ (level IV
according to WHO) or rapid decreasing leukocytes during therapy. G-CSF was
not applied during chemotherapy and terminated at least 24 h before the next
chemotherapy cycle. r-metHuG-CSF (Filgrastim, Neupogen®) was used
subcutaneously. Documented were the duration until the leukocyte increase,
neutrophil granulocytes, thrombocytes, interruption of radiotherapy, febrile
episodes and side effects. Results: In case of severe leukopenia (< 1000/mm³, n =
16) the leukocytes increased after 3 days of G-CSF application, the radiotherapy
was interrupted in 2 cases, terminated in 1 case. Four patients had fever before,
during G-CSF 4 additional febrile episodes occurred. If G-CSF application was
started between leukocyte levels of 1000 and 1500/mm3 after 1 day the leukocytes
increased in 9 of 10 cases beyond the starting level. Interruption of radiotherapy
was not necessary. Only 1 febrile episode occurred (1/11). There were no relevant
side effects of G-CSF. Conclusions: Rapidly developing or severe leukopenia
during radio(chemo)therapy are indications for an interventional application of GCSF. The leukocyte level for the start of G-CSF should be chosen so that without
G-CSF an interruption of therapy or a level IV leukopenia seems to be
unavoidable.
ND:
Autoren:
EM1997053693
Legros M; Fleury J; Bay JO; Choufi B; Basile M; Condat P; Glenat C; Communal
Y; Tavernier F; Bons JM; Chollet P; Plagne R; Chassagne J
Titel:
rhGM-CSF vs placebo following rhGM-CSF-mobilized PBPC
transplantation: A phase III double-blind randomized trial
Source:
SU:
Sprache:
AB:
EMBASE
English
In this placebo-controlled randomized trial we evaluated the hematological and
clinical effects of r-Hu GM-CSF after high-dose chemotherapy (HDC) followed
by GM-CSF-mobilized PBPC transplantation. Fifty patients with poor prognosis
malignancies were randomized in a double-blind study to receive either GM-CSF
or placebo after HDC followed by PBPC rescue. For all patients, PBPCs were
recruited using a combination of VP-16 (300 mg/m² on days 1 and 2), cytoxan (3
g/m² on days 3 and 4) and GM-CSF (5 mu g/kg from day 5). No differences were
demonstrated between the two groups in median time to neutrophil or platelet
recoveries. There was no significant difference between the GM-CSF group and
the placebo group in the duration of post-transplant hospitalization, in the number
of days of antibiotic treatment, in the number of infections and in red blood cell or
platelet transfusion requirements. There was a significant difference with an
advantage or the placebo group in the mean duration of febrile days (P = 0.01).
We conclude that the administration of GM-CSF in patients transplanted with
GM-CSF-mobilized PBPC is not associated with a clinical benefit in term of
tempo of engraftment, number of documented infections, transfusion requirements
mucositis grading.
65 von 74
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Autoren:
EM1996290274
Koenigsmann MP; Notter M; Knauf WU; Papadimitriou CA; Oberberg D; Reufi
B; Mücke C; Thiel E; Berdel WE
Titel:
Chemopurging of peripheral blood-derived progenitor cells by alkyllysophospholipid and its effect on haematopoietic rescue after highdose therapy
Source:
SU:
Sprache:
AB:
EMBASE
English
One reason for relapse after high-dose tumor therapy with subsequent autologous
stem cell transplantation is tumor cell contamination of the graft. Removal of
tumor cells from bone marrow grafts by chemopurging with the ether lipid
edelfosine has been established as an effective and simple method. When
compared with bone marrow derived grafts, progenitor cells from peripheral blood
have considerably reduced the haematological recovery times. However, this
advantage is put at risk by the nonspecific haematotoxic activity of the purging
agent. We therefore compared the in vitro recovery of peripheral blood derived
progenitor cells (PBPC) from either non-purged (n = 41) or purged (75 mu g/ml of
ether lipid for 4 h at 37°C, n = 48) leukapheresis products. The recovery of CFUGM after cryopreservation was 63 ± 4% without and 48 ± 3% with purging (P =
0.007). After high-dose therapy, patients (n = 37) received similar amounts of
either non-purged (n = 17) or purged (n = 20) autologous PBPC. The median
haematological recovery times (non-purged vs purged) to > 500 WBC/ mu l were
9.0 vs 8.5 days after transplantation, to > 2000 PMN/ mu l 10.5 vs 10.0 days, and
to > 50,000 PLT/ mu l 15.5 vs 14.0 days. All differences were statistically not
significant. We conclude that ether lipid purging of PBPC leads to a significant,
however tolerable loss of progenitor cells in vitro, and that haematological
recovery times after high-dose therapy are identically short, provided similar
amounts of PBPC are reinfused.
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Autoren:
EM1996260493
Pratt CB; Luo X; Fang L; Marina N; Avery L; Furman WL
Titel:
Response of pediatric malignant solid tumors following ifosfamide or
ifosfamide/carboplatin/etoposide: A single hospital experience
Source:
DOI:
SU:
Sprache:
AB:
67 von 74
Medical and Pediatric Oncology; VOL: 27 (3); p. 145-148 /199609/
10.1002/(SICI)1096-911X(199609)27:3<145::AID-MPO2>3.0.CO;2-E
EMBASE
English
One hundred thirty-eight pediatric patients have received treatment for malignant
solid tumors with ifosfamide with mesna, and 71 have received a combination
with ifosfamide/carboplatin/etoposide (ICE). Responses were obtained in many
types of pediatric tumors, yet comparison of responses was not possible be cause
of inadequate numbers of tumors of differing histiotypes. Comparison of results
between patients with all tumors treated with ifosfamide or ICE indicated that
there was a higher response rate for patients treated with ICE, with an estimated
odds ratio of 2.74 (95% C.I. 1.45-5.179). Excluding patients without prior
chemotherapy and radiotherapy, the odds ratio for 2.801 (95% C.I. 1.45-5.4)
suggests a similar result. There remain no guarantees that the more costly
treatment with ICE, which requires cytokine support, will offer therapeutic
benefits against resistant solid tumors.
ND:
Autoren:
EM1996218811
Chang AY; Boros L; Garrow GC; Asbury RF; Hui L
Titel:
Ifosfamide, carboplatin, etoposide, and paclitaxel chemotherapy: A
dose- escalation study
Source:
SU:
Sprache:
AB:
Seminars in Oncology; VOL: 23 (3 SUPPL. 6); p. 74-77 /1996/
EMBASE
English
Ifosfamide, carboplatin, cisplatin, etoposide, and paclitaxel are chemotherapeutic
agents active in treating many malignant diseases. The ICE combination
(ifosfamide/carboplatin [or cisplatin]/etoposide) has been studied in breast cancer,
small cell and non-small cell lung cancer, testicular cancer, lymphoma, and other
malignancies with promising results. We conducted a dose-escalation study of
paclitaxel in combination with ICE (ICE-T) to evaluate the toxicity and define the
maximum tolerated dose of paclitaxel. To date, 24 patients have been treated with
ICE-T. Patients had to have no or minimal prior chemotherapy, an Eastern
Cooperative Ontology Group performance status of 0 or 1, and adequate bone
marrow, liver, and kidney function. The doses of ICE were as follows: ifosfamide
1.25 g/m²/d days 1 to 3, carboplatin 300 mg/m² day 1, and etoposide 80 mg/m²/d
days 1 to 3. Paclitaxel was given at a dose of 120 mg/m² to five patients, 135
mg/m² to five patients, 150 mg/m² to three patients, and 175 mg/m² to 11 patients.
All patients received granulocyte colony-stimulating factor support. The most
common side effect was neutropenia. Grade 4 neutropenia and thrombocytopenia
occurred during 34% and 20% of 94 cycles, respectively, with leukopenic fever
occurring during 14% of cycles. No treatment-related death or sepsis occurred due
to brief nadir durations of 3.5 days for neutropenia and thrombocytopenia. Other
toxicities were mostly mild to moderate and did not require dose modification,
although alopecia was universal. Nine patients (100%) with metastatic breast
cancer and four (67%) with soft tissue sarcoma have attained documented
objective responses with four complete remissions (one breast cancer and three
sarcoma patients). The maximum tolerated dose of paclitaxel has not yet been
defined, and the study is ongoing. In conclusion, this pilot study showed that ICET is safe and tolerable. The response to ICE-T is encouraging and warrants further
study with this regimen.
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Autoren:
EM1996165454
Wiedemann GJ; Robins HI; Gutsche S; Mentzel M; Deeken M; Katschinski DM;
Eleftheriadis S; Crahe R; Weiss C; Storer B; Wagner T
Titel:
Ifosfamide, carboplatin and etoposide (ICE) combined with 41.8°C
whole body hyperthermia in patients with refractory sarcoma
Source:
DOI:
SU:
Sprache:
AB:
European Journal of Cancer Part A; VOL: 32 (5); p. 888-892 /1996/
10.1016/0959-8049(95)00622-2
EMBASE
English
Two earlier studies resulted in the design of a phase II trial of 41.8°C (x 60 min)
extracorporeal whole body hyperthermia (WBH) with ICE, i.e. ifosfamide (5
g/m²), carboplatin (300 mg/m²), and etoposide given with WBH, as well as, day 2
and 3 post-WBH (100 mg/m²) for adult patients with refractory sarcoma. 12
patients entered this trial; all were evaluable. 8 patients had a history of prior
chemotherapy associated with disease progression. Following WBH/ICE, 7 partial
remissions were observed (58%); 3 patients experienced disease stabilisation; the
aforementioned 10 patients each received four cycles of therapy. 2 patients
exhibited progressive disease. Episodes of WHO graded (grade 3; grade 4)
toxicity observed included: anaemia (2;2); leucopenia (5;7); thrombocytopenia
(1;6); renal (0;1). Other toxicities (grade 1 and 2) included: anasarca, diarrhoea,
ventricular arrhythmias, pressure sores, and perioral herpes simplex.
69 von 74
ND:
Autoren:
EM1996138009
Wada T; Isu K; Takeda N; Usui M; Ishii S; Yamawaki S
Titel:
A preliminary report of neoadjuvant chemotherapy NSH-7 study in
osteosarcoma: Preoperative salvage chemotherapy based on clinical
tumor response and the use of granulocyte colony-stimulating factor
Source:
SU:
Sprache:
AB:
Oncology; VOL: 53 (3); p. 221-227 /199605/
EMBASE
English
Eleven patients with high-grade osteosarcoma of an extremity were treated with
neoadjuvant chemotherapy with the NSH-7 protocol. NSH-7 is a refinement of the
T-12 Rosen protocol. Preoperative chemotherapy is initiated with a doxorubicin
(ADM) and high-dose methotrexate combination. If the primary tumor progresses
after the first cycle, the preoperative chemotherapy is switched to a combination
of cisplatin and ADM. Postoperative adjuvant chemotherapy was selected based
on histological response of the primary tumor. In addition, recombinant human
granulocyte colony-stimulating factor was used to prevent leukocytopenia and to
increase the dose intensity of the chemotherapy. In 1 patient, preoperative
chemotherapy was switched to salvage treatment. Of the 156 courses given, there
were 10 delays and 4 dose reductions. Leukocytopenia accounted for only 1 delay.
All 11 patients completed the chemotherapy and 5 patients were fully able to
tolerate the protocol without delay or dose reduction. Nine patients remained alive
and continuously free of disease at an average follow-up of 35 months. The rate of
continuous disease-free survival at 3 years was 81%, which was significantly
better than that of the T-12 study of our group. These observations suggest that the
NSH-7 protocol is a safe and effective treatment regimen for osteosarcoma.
70 von 74
ND:
Autoren:
EM1995233956
Boros L; Garrow GC; Asbury RF; Chang AY
Titel:
Phase I study of escalating doses of paclitaxel (Taxol) with fixed
doses of ifosfamide, carboplatin, and etoposide
Source:
SU:
Sprache:
AB:
EMBASE
English
The combination of ifosfamide (with mesna uroprotection), carboplatin, and
etoposide (ICE) has demonstrated activity in a variety of cancers. Paclitaxel
(Taxol; Bristol-Myers Squibb Company, Princeton, NJ), a dipertene compound
extracted from the Pacific yew Taxus brevifolia, appeared a good candidate for
study as an addition to the ICE regimen (ICE-T) because of its broad antitumor
activity, its unique mechanism of action, and its toxicity profile, which was not
expected to impact the ICE regimen adversely. In a phase I study, we evaluated
the impact of adding escalating doses of paclitaxel (120 mg/m², 135 mg/m², 150
mg/m², and 175 mg/m²) to the ICE regimen in 13 previously untreated (with two
exceptions) patients with breast cancer, sarcoma, lung cancer, and adenoid cystic
carcinoma. In general, ICE-T was well tolerated with some myelosuppression
observed. Responses were seen at all dose levels. To date, the maximal tolerated
dose of paclitaxel has not been reached; we are currently administering 175
mg/m².
71 von 74
ND:
Autoren:
EM1994286780
Marina NM; Shema SJ; Bowman LC; Rodman J; Douglass EC; Furman WL;
Pappo A; Santana VM; Hudson M; Meyer WH; Pratt CB
Titel:
Failure of granulocyte-macrophage colony-stimulating factor to
reduce febrile neutropenia in children with recurrent solid tumors
treated with ifosfamide, carboplatin, and etoposide chemotherapy
Source:
SU:
Sprache:
Medical and Pediatric Oncology; VOL: 23 (4); p. 328-334 /1994/
EMBASE
English
AB:
72 von 74
Ifosfamide, carboplatin, and etoposide (ICE) chemotherapy has promising activity
against various solid tumors but produces significant myelotoxicity that might be
ameliorated by hematopoietic growth factors. Twelve patients with relapsed solid
tumors were treated with ICE chemotherapy. Carboplatin was given on day 1 at a
targeted area under the concentration-time curve (AUC) of 8 mg/mL x min
(adjusted for each patient's glomerular filtration rate), followed by ifosfamide 2
g/m² and etoposide 100 mg/m² on days 2 through 4. Granulocyte-macrophage
colony-stimulating factor (GM-CSF), 1,000 mu g/m²/day, was started 24 hours
after each course and given for 17 days or until the absolute neutrophil count
(ANC) reached 10 x 109/L. Myelotoxicity and responses in these
patients were compared to those of eight patients who received the same therapy
without GM-CSF. Patients received a median of three courses (range, 1-8). All 20
patients developed grade 4 neutropenia and grade 3 or 4 thrombocytopenia. The
median duration of neutropenia was significantly shorter in patients who received
GM-CSF (16.75 vs. 10 days, P = 0.005). However, the two groups did not differ in
the proportion of courses associated with hospitalization for febrile neutropenia,
the duration of hospitalization, or the median duration of thrombocytopenia. There
were two complete, four partial, and three objective responses in the 12 patients
treated with ICE plus GM-CSF, and two partial and three objective responses in
the 8 patients treated with ICE only. GM-CSF did not reduce the occurrence of
febrile neutropenia or the duration of thrombocytopenia associated with ICE
chemotherapy. Studies of other hematopoietic growth factors in conjunction with
this promising combination are merited.
ND:
Autoren:
EM1994059088
Philp T; Ladenstein R; Linkesch W
Titel:
Recent aspects on the role of megatherapy followed by bone marrow
rescue in high-risk neuroblastoma, malignant brain gliomas and
poor prognosis Ewing sarcoma
Source:
SU:
Sprache:
Bone Marrow Transplantation; VOL: 12 (SUPPL. 4); p. S82-S84 /1993/
EMBASE
English
73 von 74
ND:
Autoren:
EM1994045946
McQueen KD; Milton JD
Titel:
Multicenter postmarketing surveillance of ondansetron therapy in
pediatric patients
Source:
SU:
Sprache:
AB:
Annals of Pharmacotherapy; VOL: 28 (1); p. 85-92 /1994/
EMBASE
English
OBJECTIVE: To identify prescribing patterns of ondansetron, to provide a
general overview of the therapeutic responses and possible adverse effects to
ondansetron in selected children's hospitals, and to evaluate this methodology of
surveillance and assess its effectiveness as a means to collect postmarketing
experience with a drug in pediatric patients. DESIGN: This survey examined the
use of ondansetron in 210 children. Complete drug and medical histories,
indications, doses, possible ondansetron-associated adverse reactions, and daily
responses to ondansetron therapy were recorded by a study pharmacist for each
patient. Patients were followed until discharged from the clinic or hospital and/or
until ondansetron therapy was discontinued. SETTING: The survey was
conducted in seven free-standing children's hospitals across the US. Hospitals
ranged in size from 100 to 331 beds (average 234). One hospital was located on
the West coast, one on the East coast, one in the Rocky Mountain region, one in
the Southwest region, and three in the Midwest. PARTICIPANTS: The selection
of study participants was limited to member free-standing children's hospitals of
the Pediatric Pharmacy Administrative Group. Selection was based on geographic
location and availability of a pharmacist to coordinate the study. One pharmacist
at each study site served as surveillance coordinator. Each pharmacist monitored
without intervention the use of ondansetron in 30 children. Patients were enrolled
consecutively from physicians' orders for ondansetron. Enrollment was open to
clinic and hospital patients. Patients were excluded if more than 48 hours of
retrospective review was required. MAIN OUTCOME MEASURES: The survey
queried patient demographics, type of antineoplastic therapy administered,
indications and dosing regimen(s) for ondansetron, additional antiemetic agents
administered, and clinical response. Adverse drug reactions and prescriptions for
ondansetron on discharge were recorded. An evaluation of response rates in
hospital patients based on exposure to antineoplastic regimens causing acute
(within 24 h) or delayed emesis (after 24 h) was formulated after data collection.
Off-label use was summarized. RESULTS: Surveys from 197 of the 210 patients
enrolled were complete for evaluation. Ondansetron was used to treat
chemotherapy-induced emesis in 88 percent of the patients and 12 percent
received it for various other indications. Ondansetron dosing was off-label in 15
percent and 73 percent prior to and after an emetogenic exposure, respectively.
Twenty-six percent of the patients were younger than four years. Dosages ranged
from 0.15 to 0.45 mg/kg, given in various schedules. The injectable form was
given both intravenously and orally. There was a significant difference in the
mean number of doses in hospital (9 ± 7.3) versus clinic (2 ± 1.5) patients
(p<0.0001). Eighty-seven percent of all patients had a complete or major overall
response. Possible ondansetron-associated adverse reactions were similar to those
of previous reports for all patients, although some recorded reactions are not
currently included in package labeling. CONCLUSIONS: This study documents
off-label use of ondansetron in children. Further study of ondansetron use in
children less than four years of age, and for indications other than chemotherapyinduced emesis, is needed. Additional evaluation into the most cost-effective
dosing of ondansetron would also be valuable.
74 von 74
ND:
Autoren:
EM1993045321
Loehrer PJ Sr.
Titel:
Chronic oral etoposide: Trials at Indiana University and with the
Hoosier Oncology Group
Source:
SU:
Sprache:
AB:
EMBASE
English
Etoposide has proven to be an active agent in the treatment of a variety of
neoplasms, particularly germ cell cancers and small cell lung cancer. Yet despite
its widespread use, the optimal dose and schedule for etoposide remain unknown.
The fact that its efficacy appears to be schedule dependent, along with the recent
availability of an oral formulation, formed the basis for several trials at Indiana
University and through the Hoosier Oncology Group. These trials evaluated
chronic daily administration of the drug in several malignancies. In testicular
cancer, etoposide was shown to have a possible role in adjuvant therapy for
refractory disease or as part of combination chemotherapy. In small cell lung
cancer, etoposide demonstrated activity in both previously treated and untreated
patients. The drug, however, had little impact on patients with advanced non-small
cell lung cancer, advanced melanoma, or advanced soft tissue sarcoma. Since
etoposide appears to be most effective in refractory small cell lung cancer and
germ cell tumors, we believe the drug should be explored in tumors with a known
history of chemosensitivity to conventionally administered etoposide.
Anhang 3
Recherche in www.Clinicaltrials.gov am 31.03.2011 (überprüft am18.04.2011)
Found 21 studies with search of: soft tissue sarcoma; carboplatin AND etoposide
Hide studies that are not seeking new volunteers.
Hide studies with unknown recruitment status.
Display Options
Rank
Status
Study
1
Completed
Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant
Solid Tumors
Conditions: Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor;
Extragonadal Germ Cell Tumor; Kidney Cancer; Liver Cancer; Lymphoma;
Neuroblastoma; Ovarian Cancer; Sarcoma; Testicular Germ Cell Tumor; Unspecified
Childhood Solid Tumor, Protocol Specific
Interventions: Drug: carboplatin; Drug: dasatinib; Drug: etoposide phosphate; Drug: ifosfamide;
Genetic: microarray analysis; Genetic: western blotting;
Other: immunohistochemistry staining method; Other: laboratory biomarker analysis;
Procedure: therapeutic conventional surgery; Radiation: radiation therapy
2
Unknown †
Combination Chemotherapy Plus Amifostine in Treating Patients With Metastatic or Unresectable Cancer
Conditions: Bladder Cancer; Brain and Central Nervous System Tumors;
Carcinoma of Unknown Primary; Extragonadal Germ Cell Tumor;
Head and Neck Cancer; Kidney Cancer; Lung Cancer; Ovarian Cancer; Sarcoma;
Testicular Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific
Interventions: Biological: filgrastim; Drug: amifostine trihydrate; Drug: carboplatin; Drug: etoposide;
Drug: ifosfamide; Procedure: peripheral blood stem cell transplantation
3
Recruiting
Irinotecan and Carboplatin as Upfront Window Therapy in Treating Patients With Newly Diagnosed Intermediate-Risk or
High-Risk Rhabdomyosarcoma
Condition: Sarcoma
Interventions: Biological: filgrastim; Drug: carboplatin; Drug: cyclophosphamide;
Drug: dexrazoxane hydrochloride; Drug: doxorubicin hydrochloride; Drug: etoposide;
Drug: ifosfamide; Drug: irinotecan hydrochloride; Drug: vincristine sulfate;
Procedure: conventional surgery; Radiation: radiation therapy
4
Unknown †
Surgery Followed by Chemotherapy in Treating Young Patients With Soft Tissue Sarcoma
Conditions: Childhood Malignant Fibrous Histiocytoma of Bone; Sarcoma
Interventions: Biological: dactinomycin; Drug: carboplatin; Drug: cyclophosphamide;
Drug: epirubicin hydrochloride; Drug: etoposide; Drug: ifosfamide;
Drug: vincristine sulfate; Procedure: adjuvant therapy; Procedure: conventional surgery;
Procedure: neoadjuvant therapy; Radiation: brachytherapy;
Radiation: radiation therapy
5
Completed
Neoadjuvant Adriamycin and Ifosfamide Plus High-Dose ICE in Patients With Soft Tissue Sarcoma (STS)
Condition: Sarcoma, Soft Tissue
Interventions: Drug: Adriamycin; Drug: Ifosfamide; Drug: Etoposide; Drug: Carboplatin
6
Completed
Intensive Chemo-Radiotherapy With Peripheral Blood Progenitor Cell Rescue for Children With Advanced Neuroblastoma
and Sarcomas
Conditions: Neuroblastoma; Ewings Sarcoma; Non-rhabdomyosarcoma Soft Tissue Sarcoma
Interventions: Drug: Vincristine; Drug: Cyclophosphamide; Drug: Adriamycin;
Drug: Etoposide (VP-16); Drug: Cisplatin; Drug: Carboplatin; Drug: Melphalan;
Drug: Ifosfamide; Drug: G-CSF (granulocyte-colony stimulating factor); Drug: Mesna
7
Unknown †
Combination Chemotherapy in Treating Children With Metastatic Rhabdomyosarcoma or Other Malignant Mesenchymal
Tumors
Conditions: Ovarian Cancer; Sarcoma; Small Intestine Cancer
Interventions: Biological: dactinomycin; Biological: filgrastim; Drug: carboplatin;
Drug: cyclophosphamide; Drug: doxorubicin hydrochloride;
Drug: epirubicin hydrochloride; Drug: etoposide; Drug: ifosfamide;
Drug: vincristine sulfate; Procedure: peripheral blood stem cell transplantation;
8
Unknown †
Peripheral Stem Cell Transplantation Plus Chemotherapy in Treating Patients With Malignant Solid Tumors
Conditions: Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor;
Extragonadal Germ Cell Tumor; Liver Cancer; Neuroblastoma; Ovarian Cancer;
Sarcoma; Testicular Germ Cell Tumor
Interventions: Biological: filgrastim; Drug: carboplatin; Drug: cyclophosphamide; Drug: etoposide;
Procedure: autologous bone marrow transplantation; Procedure: peripheral blood stem
cell transplantation
9
Completed
Whole-Body Hyperthermia Plus Chemotherapy in Treating Patients With Advanced Sarcoma
Condition: Sarcoma
Interventions: Drug: carboplatin; Drug: etoposide; Drug: ifosfamide;
Procedure: hyperthermia treatment
10
Active, not
recruiting
High-Dose Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Advanced
Cancer
Condition: Cancer
Interventions: Biological: filgrastim; Drug: carboplatin; Drug: cisplatin; Drug: cyclophosphamide;
Drug: etoposide; Drug: ifosfamide; Drug: mesna; Drug: paclitaxel; Procedure:
peripheral blood stem cell transplantation
11
Recruiting
Combination Chemotherapy in Treating Young Patients With Nonmetastatic Rhabdomyosarcoma
Condition: Sarcoma
Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: ifosfamide;
Drug: topotecan hydrochloride; Drug: vincristine sulfate; Drug: vinorelbine tartrate;
Procedure: conventional surgery; Radiation: radiation therapy
12
Unknown †
Colony-Stimulating Factors in Treating Children With Recurrent or Refractory Solid Tumors
Condition: Cancer
Interventions: Biological: filgrastim; Biological: recombinant human thrombopoietin;
Drug: carboplatin; Drug: etoposide; Drug: ifosfamide
13
Terminated
Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Brain
Tumor
Conditions: Brain and Central Nervous System Tumors; Neuroblastoma; Retinoblastoma; Sarcoma
Drug: etoposide; Drug: leucovorin calcium; Drug: methotrexate; Drug: temozolomide;
Drug: thiotepa; Drug: vincristine sulfate;
Procedure: autologous bone marrow transplantation; Procedure: peripheral blood stem
cell transplantation; Radiation: radiation therapy
14
Active, not
recruiting
Chemotherapy Followed by Surgery and Radiation Therapy With or Without Stem Cell Transplant in Treating Patients
With Relapsed or Refractory Wilms' Tumor or Clear Cell Sarcoma of the Kidney
Condition: Kidney Cancer
Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: melphalan;
Drug: vincristine sulfate; Procedure: autologous bone marrow transplantation;
Procedure: conventional surgery; Procedure: peripheral blood stem cell transplantation;
15
Recruiting
Combination Chemotherapy, Radiation Therapy, and/or Surgery in Treating Patients With High-Risk Kidney Tumors
Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: irinotecan hydrochloride;
Drug: vincristine sulfate; Procedure: conventional surgery; Radiation: radiation therapy
16
Completed
Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Infants With Malignant Brain or Spinal Cord Tumors
Conditions: Brain and Central Nervous System Tumors; Neuroblastoma; Sarcoma
Drug: etoposide; Drug: thiotepa; Drug: vincristine sulfate;
Procedure: conventional surgery; Procedure: peripheral blood stem cell transplantation
17
Terminated
Rhabdomyosarcoma and Malignant Soft Tissue Tumours of Childhood
Conditions: Rhabdomyosarcoma; Malignant Soft Tissue
Intervention: Drug: Ifosfamide, oncovin, actinomycine D, epirubicine, carboplatinum, etoposide
18
Completed
Chemotherapy With or Without Surgery, Radiation Therapy, or Stem Cell Transplantation in Treating Young Patients
With Kidney Tumors
Interventions: Biological: dactinomycin; Biological: filgrastim; Drug: carboplatin;
Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: etoposide;
Drug: vincristine sulfate; Procedure: conventional surgery; Radiation: radiation therapy
19
Recruiting
Intravenous Palifosfamide-tris in Combination With Etoposide and Carboplatin in Patients With Malignancies
Conditions: Malignancy; Cancer; Non Small Cell Lung Cancer; Small Cell Lung Cancer;
Testicular Cancer; Thymoma; Ovarian Cancer; Osteosarcoma
Intervention: Drug: palifosfamide-tris
20
21
Completed
Recruiting
Recombinant Human Thrombopoietin in Children Receiving Ifosfamide, Carboplatin, and Etoposide Chemotherapy
Conditions: Germ Cell Tumors; Hepatic Cancer; Neuroblastoma; Osteosarcoma;
Rhabdomyosarcoma
Intervention: Drug: Recombinant Human Thrombopoietin
Tandem Peripheral Blood Stem Cell (PBSC) Rescue for High Risk Solid Tumors
Conditions: Ewing's Sarcoma; Soft Tissue Sarcoma; Hepatoblastoma; Hodgkin's Disease;
Germ Cell Tumor
Intervention: Drug: High-Dose Chemotherapy with Tandem PBSC Rescue.
Anhang 4
Recherche am 18.04.2011 in Cochrane Database
Suchbegriffe: soft tissue sarcoma, etoposide, carboplatin
Treffer 3
Record #1 of 3
ID: CN-00766449
AU: Odile Oberlin
AU: Annie Rey
AU: Jose Sanchez de Toledo
AU: Caroline Ellershaw
AU: Natahlie Bouvet
AU: Meriel Jenney
AU: Marie José Terrier-Lacombe
AU: Mike Stevens
TI: SIOP MMT 95: INTENSIFIED (6 DRUG) VERSUS STANDARD (IVA) CHEMOTHERAPY
FOR HIGH RISK NON METASTATIC SOFT TISSUE SARCOMA (STS)
OT: 40th Annual Conference of the International Society of Paediatric Oncology, SIOP 2008, Berlin,
Germany, Abstract O.103
SO: Pediatr Blood Cancer
YR: 2008
VL: 50
NO: 5(supplement)
PG: 47
US: http://www.mrw.interscience.wiley.com/cochrane/clcentral/articles/449/CN-00766449/frame.html
CC: HS-CHILDCA; SR-CHILDCA; HS-HANDSRCH
Record #2 of 3
ID: CN-00623199
AU: Stohr W
AU: Paulides M
AU: Brecht I
AU: Kremers A
AU: Treuner J
AU: Langer T
AU: Beck JD
TI: Comparison of epirubicin and doxorubicin cardiotoxicity in children and adolescents treated within
the German Cooperative Soft Tissue Sarcoma Study (CWS).
SO: Journal of Cancer Research and Clinical Oncology
YR: 2006
VL: 132
NO: 1
PG: 35-40
XR: EMBASE 2005543740
PT: Journal: Article
DE: CCT
KY: Adolescent; Article; *Cancer Combination Chemotherapy; Cancer Diagnosis; Cardiomyopathy;
Dt [Drug Therapy]; Cardiomyopathy; Si [Side Effect]; *Cardiotoxicity; Dt [Drug Therapy];
*Cardiotoxicity; Si [Side Effect]; Clinical Trial; Confidence Interval; Controlled Study;
Echocardiography; Female; Follow up; Heart Function; Heart Left Ventricle Function; High Risk
Patient; Human; Incidence; Major Clinical Study; Male; Multicenter Study; Priority Journal;
Randomized Controlled Trial; *Soft Tissue Sarcoma; Dt [Drug Therapy]; Treatment Outcome;
Carboplatin; Cb [Drug Combination]; Carboplatin; Dt [Drug Therapy]; Dactinomycin; Cb [Drug
Combination]; Dactinomycin; Dt [Drug Therapy]; Dipeptidyl Carboxypeptidase Inhibitor; Dt [Drug
Therapy]; *Doxorubicin; Ae [Adverse Drug Reaction]; *Doxorubicin; Ct [Clinical Trial];
*Doxorubicin; Cb [Drug Combination]; *Doxorubicin; Cm [Drug Comparison]; *Doxorubicin; Dt
[Drug Therapy]; *Epirubicin; Ae [Adverse Drug Reaction]; *Epirubicin; Ct [Clinical Trial];
*Epirubicin; Cb [Drug Combination]; *Epirubicin; Cm [Drug Comparison]; *Epirubicin; Dt [Drug
Therapy]; Etoposide; Cb [Drug Combination]; Etoposide; Dt [Drug Therapy]; Ifosfamide; Cb [Drug
Combination]; Ifosfamide; Dt [Drug Therapy]; Vincristine; Cb [Drug Combination]; Vincristine; Dt
[Drug Therapy]
Record #3 of 3
ID: CN-00501873
AU: Van Winkle P
AU: Angiolillo A
AU: Krailo M
AU: Cheung YK
AU: Anderson B
AU: Davenport V
AU: Reaman G
AU: Cairo MS
TI: Ifosfamide, carboplatin, and etoposide (ICE) reinduction chemotherapy in a large cohort of
children and adolescents with recurrent/refractory sarcoma: the Children's Cancer Group (CCG)
experience.
SO: Pediatric blood & cancer
YR: 2005
VL: 44
NO: 4
PG: 338-47
PM: PUBMED 15503297
PT: Clinical Trial; Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Randomized
Controlled Trial; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
AD: Childrens Hospital of Los Angeles, Los Angeles, California, USA.
KY: Adolescent; Antineoplastic Combined Chemotherapy Protocols [therapeutic use]; Carboplatin
[administration & dosage]; Colony-Stimulating Factors [administration & dosage]; Etoposide
[administration & dosage]; Ifosfamide [administration & dosage]; Multivariate Analysis; Proportional
Hazards Models; Recurrence; Rhabdomyosarcoma [drug therapy] [mortality]; Sarcoma [drug therapy]
[mortality]; Survival Rate; Adult; Child; Child, Preschool; Female; Humans; Male
CC: SR-CHILD; SR-CHILDCA
Tabelle 3
Recherche EMBASE bei DIMDI am 29.03.2011
Schlagwörter: etoposid AND carboplatin AND sarcoma AND clinical trial AND adult
Autor
Titel
1
Thiery-Vuillemin A
2
Srinivasan N; Pakala A; Mukkamalla C; Oswal A
3
Kasper B; Scharrenbroich I; Schmitt T; Wuchter
P; Dietrich S; Ho AD; Egerer G
4
McDowell HP; Foot ABM; Ellershaw C; Machin
D; Giraud C; Bergeron C
5
Fritsch P; Schwinger W; Schwantzer G; Lackner
H; Sovinz P; Wendelin G; Benesch M;
Sipurzynski S; Urban C
6
Merchant MS; Mackall CL
Current approach to pediatric soft tissue
sarcomas
Oncologist; VOL: 14
(11); p. 1139-1153 /2009
7
Mattke AC; Bailey EJ; Schuck A; Dantonello T;
Leuschner I; Klingebiel T; Treuner J; Koscielniak
E
Lieu C; Chow L; Pierson AS; Eckhardt SG;
O’Bryant CL; Morrow M; Tran ZV; Wright JJ;
Gore L
Does the time-point of relapse influence
outcome in pediatric rhabdomyosarcomas?
Pediatric Blood and
Cancer; VOL: 52 (7);
p. 772-776
Investigational New
Drugs; VOL: 27 (1);
p. 53-62 /February 2009
8
Duration: Escalation study of oral etoposide
with carboplatin in patients with varied solid
tumors
Pineal germinoma
Quelle
Consolidation with high-dose chemotherapy
and stem cell support for responding patients
with metastatic soft tissue sarcomas:
Prospective, single-institutional phase II study
Outcomes in paediatric metastatic rhabdomyosarcoma: Results of The International
Society of Paediatric Oncology (SIOP) study
MMT-98
Peripheral blood stem cell mobilization with
Pegfilgrastim compared to Filgrastim in
children and young adults with malignancies
A phase i study of bortezomib, etoposide and
carboplatin in patients with advanced solid
tumors refractory to standard therapy
Anti-Cancer Drugs;
VOL: 21 (10); p. 958-962
/November 2010
Southern Medical
Journal; VOL: 103 (10);
p. 1031-1037 /October
2010
Bone Marrow
Transplantation;
VOL: 45 (7); p. 12341238 /July 2010
European Journal of
p. 1588-1595 /June
2010
Pediatric Blood and
p. 134-137 /January
2010
Bemerkung/
Begründung für
Nichtberücksichtigung
Dosis-EskalationsStudie, Phase I
Anderer Tumor
(Germinom)
Single-Centre
prospective study,
phase II, 34 Patienten,
andere Chemotherapie
Pädiatrische Patienten,
Pädiatrische Patienten,
Studie mit Pegfilgrastim
Pädiatrie,
Keine Studie,
Übersichtsarbeit
Pädiatrische
Fragestellung,
Keine Studie,
Andere Chemotherapie
9
Ramondetta LM; Johnson AJ; Sun CC; Atkinson
N; Smith JA; Jung MS; Broaddus R; Iyer RB;
Burke T
10
Bielack SS; Carrle D; Hardes J; Schuck A;
Paulussen M
11
Weitberg AB
A phase I/II trial of beta-(1,3)/(1,6) D-glucan in
the treatment of patients with advanced
malignancies receiving chemotherapy
12
Pearson AD; Pinkerton CR; Lewis IJ; Imeson J;
Ellershaw C; Machin D
13
Schuster MW; Shore TB; Harpel JG; Greenberg
J; Jalilizeinali B; Possley S; Gerwien RW; Hahne
W; Halvorsen Y-DC
14
Ozkaynak MF; Sahdev I; Gross TG; Levine JE;
Cheerva AC; Richards MK; Rozans MK; Shaw
PJ; Kadota RP
15
Dohnal AM; Witt V; Hügel H; Holter W; Gadner
H; Felzmann T
16
Nieto Y; Aldaz A; Rifón J; Pérez-Calvo J; Zafra
A; Zufia L; Viúdez A; Viteri S; Aramendía JM;
Aristu J; Centeno C; Moreno M; Sayar O;
Hernández M
17
Syed R; Bomanji JB; Nagabhushan N; Kayani I;
Groves A; Waddington W; Cassoni A; Ell PJ
High-dose rapid and standard induction
chemotherapy for patients aged over 1 year
with stage 4 neuroblastoma: a randomised
trial
Safety and tolerability of velafermin
(CG53135-05) in patients receiving high-dose
chemotherapy and autologous peripheral
blood stem cell transplant
A pilot study of addition of amifostine to
melphalan, carboplatin, etoposide, and
cyclophosphamide with autologous
hematopoietic stem cell transplantation in
pediatric solid tumors - A pediatric blood and
marrow transplant consortium study
Phase I study of tumor Ag-loaded IL-12
secreting semi-mature DC for the treatment of
pediatric cancer
Phase I and Pharmaco-kinetic Study of Gemcitabine Administered at Fixed-Dose Rate,
Com-bined with Docetaxel/ Melphalan/
Carboplatin, with Autologous Hematopoietic
Progenitor-Cell Support, in Patients with
Advanced Refractory Tumors
186Re-HEDP in the treatment of
patients with inoperable osteosarcoma
Phase 2 trial of mifepristone (RU-486) in
advanced or recurrent endometrioid
adenocarcinoma or low-grade endometrial
stromal sarcoma
Bone tumors in adolescents and young adults
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Anderer Tumor, andere
Chemotherapie
Current Treatment
Options in Oncology;
VOL: 9 (1); p. 67-80
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Journal of Experimental
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The Lancet Oncology;
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Bone tumors
Studie zu D-Glucan
Neuroblastome in der
Pädiatrie
Supportive Care in
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Studie zu Valefermib
Journal of Pediatric
Hematology/Oncology;
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Studie zu Amifostin
Cytotherapy; VOL: 9 (8);
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Journal of Nuclear
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Osteosarkoma
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Seibel NL; Krailo M; Chen Z; Healey J; Breitfeld
PP; Drachtman R; Greffe B; Nachman J; Nadel
H; Sato JK; Meyers PA; Reaman GH
19
Schlemmer M; Wendtner C-M; Falk M; AbdelRahman S; Licht T; Baumert J; Straka C;
Hentrich M; Salat C; Hiddemann W; Issels R-D
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Fine RL; Shah SS; Moulton TA; Yu I-R;
Fogelman DR; Richardson M; Burris HA;
Samuels BL; Assanasen C; Gorroochurn P;
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Dubovsky D; Walterhouse D; Halligan G
Wagner LM; McAllister N; Goldsby RE; Rausen
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K
Schneider B; Fukunaga A; Murry D; Yoder C;
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Secondino S; Selle F; Ketterer N; Grignani G;
Siena S; Demirer T
Frickhofen N; Berdel WE; Opri F; Haas R;
Schneeweiss A; Sandherr M; Kuhn W; Hossfeld
DK; Thomssen C; Heimpel H; Kreienberg R;
Hinke A; Möbus V
Kuzhan O; Arpaci F; Özet A; Öztürk B; Kömürcü
S
25
26
Upfront window trial of topotecan in previously
untreated children and adolescents with poor
prognosis metastatic osteosarcoma:
Children's Cancer Group (CCG) 7943
Efficacy of consolidation high-dose chemotherapy with ifosfamide, carbo-platin and
etoposide (HD-ICE) followed by autologous
peripheral blood stem cell rescue in
chemosensitive patients with metastatic soft
tissue sarcomas
Androgen and c-Kit receptors in desmoplastic
small round cell tumors resistant to
chemotherapy: Novel targets for therapy
Temozolomide and intravenous irinotecan for
treatment of advanced Ewing sarcoma
A phase I, pharmaco-kinetic and pharmacodynamic dose escalation trial of weekly
paclitaxel with interferon- alpha 2b in patients
with solid tumors
Improving outcomes after relapse in Ewing's
sarcoma: Analysis of 114 patients from a
single institution
High dose chemotherapy with autologous
hematopoietic stem cell support for solid
tumors other than breast cancer in adults
Phase I/II trial of multicycle high-dose
chemotherapy with peripheral blood stem cell
support for treatment of advanced ovarian
cancer
Delayed molgramostim administration after
au-tologous peripheral blood stem cell
transplantation does not add any benefit
regarding hematological engraftment and
suppor-tive therapy require-ments: A
prospective randomized trial
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Osteosarkoma
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Zusätzliche Zytostatika
Cancer Chemotherapy
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Anderer Tumor
Pediatric Blood and
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Cancer Chemotherapy
and Pharmacology;
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Ewing-Sarkoma,
Sarcoma; VOL: 2006
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Ewing-Sarkoma
Annals of Oncology;
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Anderes Thema,
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Turkish Journal of
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Studie zu Molgramostim
27
Eselgrim M; Grunert H; Kühne T; Zoubek A;
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28
Zaucha RE; Buckner DC; Barnett T; Holmberg
LA; Gooley T; Hooper HA; Maloney DG;
Appelbaum F; Bensinger WI
29
Ashihara E; Shimazaki C; Okano A; Hatsuse M;
Okamoto A; Shimura K; Takahashi R;
Sumikuma T; Inaba T; Fujita N; Murakami S;
Haruyama H; Nakagawa M
Goldstein-Jackson SY; Gosheger G; Delling G;
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31
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Basbozkurt M; Ozcan A; Komurcu S; Ozturk B;
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35
Dose intensity of chemo-therapy for
osteosarcoma and outcome in the
Cooperative Osteo-sarcoma Study Group
(COSS) trials
Modified total body irradiation as a planned
second high-dose therapy with stem cell
infusion for patients with bone-based
malignancies
Infusion of a high num-ber of CD34+ cells provides a rapid hemato-poietic recovery and cost
savings in autologous peripheral blood stem
cell transplantation
Extraskeletal osteo-sarcoma has a favourable
prognosis when treated like conventional
osteosarcoma
The feasibility of neo-adjuvant high-dose chemotherapy and auto-logous peripheral blood
stem cell transplantation in patients with nonmetastatic high grade localized osteosarcoma:
Results of a phase II study
Phase I and pharmaco-kinetic study of
docetaxel combined with melpha-lan and
carboplatin, with autologous hematopoietic
progenitor cell support, in patients with
advanced refractory malignancies
Clinical perspective on desmoplastic small
round-cell tumor
Fermented wheat germ extract reduces
chemo-therapy-induced febrile neutropenia in
pediatric cancer patients
Ifosfamide, carboplatin and etoposide (ICE) as
second-line regimen alone and in combination
with regional hyperthermia is active in chemopre-treated advanced soft tissue sarcoma of
adults
Pediatric Blood and
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Osteosarkoma
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Biology Physics;
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Japanese Journal of
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Journal of Cancer
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Osteosarkoma
Biology of Blood and
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Andere Chemotherapie,
Phase I
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VOL: 26 (10); p. 631-635
International Journal of
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Andere Therapie
Osteosarkoma
Osteosarkoma
Andere Fragestellung,
Pädiatrie
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Recchia F; De Fillipis S; Piccinini M; Rea S
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Vörding PZ; Van Dijk JDP; Finet J; Neumann A;
Longo W; Bakhshandeh A; Tiggelaar CL; Gillis
W; Bailey H; Peters SO; Robins HI
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43
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44
Matsubara H; Makimoto A; Higa T; Kawamoto
H; Takayama J; Ohira M; Yokoyama R; Beppu
Y; Takaue Y
45
Newton HB; Slivka MA; Volpi C; Bourekas EC;
Christoforidis GA; Baujan MA; Slone W;
Chakeres DW
Arpaci F; Dogru T; Ozturk B; Komurcu S; Ozet
A; Yilmaz MI; Beyzadeoglu M; Turan M; Sengul
A; Yalcin A
46
Staged autologous peri-pheral blood
progenitor cell transplantation for Ewing
sarcoma and rhabdomyosarcoma
Incidence and severity of ifosfamide-induced
encephalopathy
High-dose Carboplatin, Cyclophosphamide,
Etoposide with Hema-tological Growth
Factors, without Stem Cell Support in Patients
with Advanced Cancer
Ifosfamide in urologic cancer
The association of P-gly-coprotein with
response to chemotherapy and clinical
outcome in patients with osteo-sarcoma: A
meta-analysis
A systemic hyperthermia oncologic working
group trial: Ifosfamide, carbo-platin, and
etoposide combined with 41.8°C whole-body
hyper-thermia for metastatic soft tissue
sarcoma
A phase II study of docetaxel in patients with
relapsed and refractory Ewing's tumours
GM-CSF versus G-CSF: Engraftment characteristics, resource uti-lization, and cost
following autologous PBSC transplantation
Possible benefits of high-dose chemotherapy
as intensive consolidation in patients with
high-risk rhabdomyosarcoma who achieve
complete re-mission with conven-tional
chemotherapy
Intra-arterial carboplatin and intravenous
etopo-side for the treatment of mtastatic brain
tumors
Changes in immuno-logical recovery in
patients who received post-transplant G-CSF
or GM-CSF after auto-logous peripheral blood
stem cell transplantation (PBSCT)¹
Internal Medicine
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Anti-Cancer Drugs;
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Anticancer Research;
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Andere Therapie,
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Anderer Tumor,
Osteosarkoma,
andere Fragestellung
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Zusätzliche Zytostatika,
plus Hyperthermie
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Cytotherapy; VOL: 4 (6);
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Ewing-Sarkoma
Pediatric Hematology
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Zusätzliche Zytostatika,
Pädiatrie
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Anderer Tumor
Anderes Thema, andere
Chemotherapie
Andere Fragestellung
Andere Therapie
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Treuner J; Scarzello G; Colombatti R; De Zen L;
Pinkerton CR
Atra A; Pinkerton R
Intensive chemotherapy for children and
young adults with metastatic primitive
neuroecto-dermal tumors of the soft tissue
High-dose chemotherapy in soft tissue
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Meazza C; Gronchi A; Ceccheto G; Fidani P;
Kunz D; Treuner J; Carli M
Hemangiopericytoma in pediatric ages: A
report from the Italian and German Soft Tissue
Sarcoma Cooperative Group
50
Kushner BH; Cheung N-KV; Kramer K; Dunkel
IJ; Calleja E; Boulad F
51
Hartmann JT; Vangerow Avon; Fels LM; Knop
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52
Merimsky O; Meller I; Kollender Y; Issakov J;
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Figuerres E; Haut PR; Olzewski M; Kletzel M
Topotecan combined with myeloablative does
of thiotepa and carbo-platin for
neuroblastoma, brain tumors, and other poorrisk solid tumors in children and young adults
A randomized trial of amifostine in patients
with high-dose VIC chemotherapy plus
autologous blood stem cell transplanation
Gemcitabine in bone sarcoma resistant to
doxorubicin-based chemotherapy
Analysis of parameters affecting engraftment
in children undergoing autologous peripheral
blood stem cell transplants
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Prognostic factors of peripheral blood stem
cell mobilization with cyclophosphamide and
Filgrastim (r-metHuG-CSF): The CD34
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hematopoietic recovery and supportive
requirements after high-dose chemotherapy
High-dose melphalan with autologous stemcell rescue in metastatic rhabdomyosarcoma
Double-alkylator non-total-body irradiation
regimen with autologous hematopoietic stemcell transplantation in pediatric solid tumors
Clinical effects and pharmacokinetics of the
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Bone Marrow
Transplantation;
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VOL: 41 (2); p. 191-196
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Bone Marrow
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British Journal of
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Sarcoma; VOL: 4 (1-2);
p. 7-10 /2000
Bone Marrow
Transplantation;
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Hematology; VOL: 4 (3);
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Journal of Clinical
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Journal of Clinical
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Cancer Chemotherapy
and Pharmacology;
Pädiatrie
Pädiatrie,
andere Fragestellung,
Behandlung kombiniert
mit Radiotherapie
Andere Therapie
Osteosarcoma
Pädiatrie,
andere Therapie
Andere Therapie
Andere Therapie
Pädiatrie, andere
Therapie
Pädiatrie, andere
Therapie
CB; Meyer WH
myelosuppressive chemotherapy
58
Charuruks N; Voravud N; Sriuranpong V
MPXI and early neutron-philia: New potential
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Bramwell VHC
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Graham ML; Herndon II JE; Casey JR; Chaffee
S; Ciocci GH; Krischer JP; Kurtzberg J; Laughlin
MJ; Lonqee DC; Olson JF; Paleologus N;
Pennington CN; Friedman HS
Weaver CH; Schwartzberg LS; Hainsworth J;
Greco FA; Li W; Buckner CD; West WH
The role of chemo-therapy in the management of non-metastatic operable extremity
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High-dose chemotherapy with autologous
stem-cell rescue in patients with recurrent and
high-risk pediatric brain tumors
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Riepl M; Fietkau R; Sauer R
Legros M; Fleury J; Bay JO; Choufi B; Basile M;
Condat P; Glenat C; Communal Y; Tavernier F;
Bons JM; Chollet P; Plagne R; Chassagne J
Koenigsmann MP; Notter M; Knauf WU;
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C; Thiel E; Berdel WE
Pratt CB; Luo X; Fang L; Marina N; Avery L;
Furman WL
Treatment-related morta-lity in 1000
consecutive patients receiving high-dose
chemotherapy and peripheral blood progenitor cell transplantation in community cancer
centers
Peripheral blood stem cell and bone marrow
transplantation for solid tumors and
lymphomas: Hematologic recovery and costs:
A randomized, controlled trial
G-CSF bei Radiochemotherapie
G-CSF in radiochemotherapy
rhGM-CSF vs placebo following rhGM-CSFmobilized PBPC transplantation: A phase III
double-blind randomized trial
Chemopurging of peripheral blood-derived
progenitor cells by alkyl-lysophospholipid and
its effect on haematopoietic rescue after highdose therapy
Response of pediatric malignant solid tumors
following ifosfamide or
ifosfamide/carboplatin/etoposide: A single
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Journal of Clinical
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Seminars in Oncology;
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Journal of Clinical
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Vorstellung neuartiger
Biomarker
Osteosarcoma
Pädiatrie, andere
Therapie
Bone Marrow
Transplantation;
VOL: 19 (7); p. 671-678
andere Therapie
Annals of Internal
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p. 600-607
andere Therapie
Strahlentherapie und
Onkologie; VOL: 173 (2);
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andere Therapie
Bone Marrow
Transplantation;
VOL: 19 (3); p. 209-213
Bone Marrow
Transplantation;
VOL: 18 (3); p. 549-557
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Medical and Pediatric
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Ifosfamide, carboplatin, etoposide, and
paclitaxel chemotherapy: A dose- escalation
study
Ifosfamide, carboplatin and etoposide (ICE)
combined with 41.8°C whole body
hyperthermia in patients with refractory
sarcoma
A preliminary report of neoadjuvant
chemotherapy NSH-7 study in osteosarcoma:
Preoperative salvage chemotherapy based on
clinical tumor response and the use of
granulocyte colony-stimulating factor
Phase I study of escalating doses of paclitaxel
(Taxol) with fixed doses of ifosfamide,
carboplatin, and etoposide
Failure of granulocyte-macro-phage colonystimulating factor to reduce febrile neutropenia
in children with recurrent solid tumors treated
with ifosfamide, carboplatin, and etoposide
chemotherapy
Recent aspects on the role of megatherapy
followed by bone marrow rescue in high-risk
neuroblastoma, malignant brain gliomas and
poor prognosis Ewing sarcoma
Multicenter postmarketing surveillance of
ondansetron therapy in pediatric patients
Chronic oral etoposide: Trials at Indiana
University and with the Hoosier Oncology
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European Journal of
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Osteosarcoma
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Medical and Pediatric
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Bone Marrow
Transplantation;
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VOL: 28 (1); p. 85-92
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Ewing-Sarkome
Pädiatrie, andere
Therapie
Pädiatrie, andere
Therapie
Andere Tumore

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