A phase I trial of liposomal doxorubicin, paclitaxel and valspodar (PSC-833), an inhibitor of multidrug resistance.
Ann Oncol
; 16(12): 1968-73, 2005 Dec.
Article
em En
| MEDLINE
| ID: mdl-16126736
ABSTRACT
PURPOSE:
The aim of this study was to determine (i) the maximum tolerated dose (MTD) of liposomal doxorubicin (L-DOX) and paclitaxel (DP), (ii) the MTD of DP plus valspodar (DPV) and (iii) pharmacokinetic (PK) interactions of valspodar with L-DOX and paclitaxel.METHODS:
Twenty-three patients with metastatic cancers received DP, followed 4 weeks later by DPV. Dose levels of DP were (mg/m2 for L-DOX/paclitaxel) 30/135 (n = 7), 30/150 (n = 4), 35/150 (n = 8) and 40/150 (n = 4). Dose levels of DPV were 15/70 (n = 10) and 15/60 (n = 10). Serial, paired PK studies were performed.RESULTS:
The MTD of DP was 40/150. For DPV at 15/70, five of 10 patients experienced grade 4 neutropenia. In the next cohort, a reduced dose of 15/60 was well tolerated. Valspodar produced reversible grade 3 ataxia in seven patients, requiring dose reduction from 5 to 4 mg/kg. Paired PK studies indicated no interaction between L-DOX and valspodar, and a 49% increase in the median half-life of paclitaxel. Two partial and one minor remissions were noted.CONCLUSIONS:
The use of valspodar necessitated dose reductions of DP, with neutropenia being dose limiting. Valspodar PK interactions were observed with paclitaxel but not L-DOX.
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Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
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Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
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Resistência a Múltiplos Medicamentos
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Resistencia a Medicamentos Antineoplásicos
/
Neoplasias
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Risk_factors_studies
Limite:
Adult
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Aged
/
Aged80
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Ann Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos