Phase I trial to investigate the safety, pharmacokinetics and efficacy of sorafenib combined with docetaxel in patients with advanced refractory solid tumours.
Eur J Cancer
; 48(4): 465-74, 2012 Mar.
Article
en En
| MEDLINE
| ID: mdl-22285181
ABSTRACT
AIM:
The safety, pharmacokinetics and efficacy of sorafenib plus docetaxel in patients with advanced refractory cancer were investigated in a phase I, dose-escalation trial.METHODS:
Twenty-seven patients in four cohorts received docetaxel on day 1 (cohorts 1 and 4 75 mg/m2; cohorts 2 and 3 100 mg/m2) plus sorafenib on days 2-19 (cohorts 1 and 2 200 mg twice-daily (bid); cohorts 3 and 4 400 mg bid) in 21-day cycles.RESULTS:
Most common adverse events (AEs) (grade 3-5) included neutropenia (89%), leucopaenia (81%), hand-foot skin reaction (30%) and fatigue (30%). The most common drug-related AEs leading to dose reduction/interruption or permanent discontinuation were dermatologic (41%), gastrointestinal (26%) and constitutional (22%). Coadministration of sorafenib altered the pharmacokinetics of docetaxel. On average, docetaxel area under the concentration-time curve (AUC)(0-24) increased by 5% (cohort 1), 54% (cohort 2), 36% (Cohort 3) and 80% (cohort 4) with docetaxel plus sorafenib, while C(max) increased by 16-32%, independent of sorafenib/docetaxel doses. Three of 25 evaluable patients (11%) had partial responses; 14 (52%) had stable disease.CONCLUSION:
Dose-limiting dermatologic AEs were more common than expected for either therapy alone. A starting dose of docetaxel 75 mg/m2 plus sorafenib 400mg bid (with dose reductions for dermatological toxicities) is proposed for phase II.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Piridinas
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Bencenosulfonatos
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Protocolos de Quimioterapia Combinada Antineoplásica
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Taxoides
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Neoplasias
Tipo de estudio:
Etiology_studies
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Incidence_studies
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Observational_studies
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Risk_factors_studies
Límite:
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
Revista:
Eur J Cancer
Año:
2012
Tipo del documento:
Article
País de afiliación:
Bélgica