A phase I study of oral topotecan and pegylated liposomal doxorubicin (doxil) in platinum-resistant ovarian and peritoneal cancer.
Am J Clin Oncol
; 31(5): 476-80, 2008 Oct.
Article
en En
| MEDLINE
| ID: mdl-18838885
OBJECTIVES: The feasibility, safety, and preliminary efficacy of a second-line combination therapy for oral topotecan and pegylated liposomal doxorubicin in patients with platinum-resistant or refractory epithelial ovarian, peritoneal, or tubal carcinoma were investigated in this phase I trial. METHODS: A fixed dose of oral topotecan 2.3 or 1.53 mg/m(2) on days 1 through 5 and escalating doses of pegylated liposomal doxorubicin on day 1 of a 28-day cycle were administered. Dose-limiting toxicities and maximum tolerated doses were recorded. Safety was assessed by adverse event monitoring, and complete and partial responses were recorded. RESULTS: Twenty-two patients received a total of 61 courses of therapy. The maximum tolerated dose of combination therapy was 1.53 mg/m(2) of topotecan on days 1 through 5 and 40 mg/m(2) of pegylated liposomal doxorubicin on day 1 of a 28-day cycle. Because of cumulative thrombocytopenia, the dose of topotecan was decreased by one-third from 2.3 to 1.53 mg/m(2) in an effort to increase the dose of pegylated liposomal doxorubicin. Only 5 patients completed >4 cycles of therapy. The most common grade 4 adverse events at dose level 4 were neutropenia (5/9 patients) and leukopenia (2/9 patients). Overall responses were observed in 2 of 22 patients. CONCLUSIONS: Oral topotecan and pegylated liposomal doxorubicin can be combined at doses that are active as monotherapies. However, the overall response rates after monotherapy in patients with platinum-resistant ovarian cancer are comparable to or higher than those observed in this phase I study of combination therapy.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Compuestos Organoplatinos
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Neoplasias Ováricas
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Neoplasias Peritoneales
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Protocolos de Quimioterapia Combinada Antineoplásica
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Resistencia a Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Am J Clin Oncol
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos