A dose-finding and pharmacodynamic study of bortezomib in combination with weekly paclitaxel in patients with advanced solid tumors.
Cancer Chemother Pharmacol
; 66(1): 151-8, 2010 May.
Article
em En
| MEDLINE
| ID: mdl-19774377
ABSTRACT
PURPOSE:
A phase I study to determine the maximum tolerated dose (MTD) of bortezomib (B) when combined with weekly paclitaxel in patients with advanced solid tumors. PATIENTS ANDMETHODS:
Eligible patients received escalating doses of intravenous (IV) bortezomib (0.6-2 mg/m(2)) on days 2 and 9 and IV paclitaxel at 100 mg/m(2) on days 1 and 8 of a 21-day cycle. Dose escalation was based on two end-points not exceeding 80% 20S-proteasome inhibition (20-S PI) and the development of dose-limiting toxicity defined as grade 3 or greater non-hematologic or grade 4 hematologic toxicities.RESULTS:
Forty-five patients with advanced solid tumors and a median of 3 prior chemotherapy regimens (range 0-9), received 318 doses (median 5, range 1-34) of bortezomib and paclitaxel. Dose-related inhibition of 20-S PI was observed with a maximum inhibition of 70-80% at the MTD of 1.8 mg/m(2) of bortezomib. At the MTD (N = 9) the following toxicities were observed grade 4 neutropenia without fever (n = 2) and cerebrovascular ischemia (n = 1); grade 3 neutropenia (n = 3), diarrhea (n = 2), nausea (n = 1), and fatigue (n = 1); grade 2 fatigue (n = 5), diarrhea (n = 4), and dyspnea (n = 2). There was one partial response in a patient with an eccrine porocarcinoma. Stabilization of disease was observed in 7 (16%) patients, 3 of whom had advanced pancreatic cancer.CONCLUSION:
Sequential paclitaxel and bortezomib in previously treated patients with advanced solid tumors resulted in acceptable toxicity and no evidence of interaction. The recommended phase II dose of bortezomib in combination with weekly paclitaxel was 1.8 mg/m(2).
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirazinas
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Ácidos Borônicos
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Protocolos de Quimioterapia Combinada Antineoplásica
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Paclitaxel
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Metástase Neoplásica
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Neoplasias
Tipo de estudo:
Diagnostic_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article