Pharmacokinetic study of the phase III, randomized, double-blind, multicenter trial (TRIBUTE) of paclitaxel and carboplatin combined with erlotinib or placebo in patients with advanced Non-small Cell Lung Cancer (NSCLC).
Invest New Drugs
; 29(3): 499-505, 2011 Jun.
Article
em En
| MEDLINE
| ID: mdl-20094773
ABSTRACT
PURPOSE:
To assess the pharmacokinetics and evaluate potential drug-drug interactions between erlotinib, paclitaxel and carboplatin. EXPERIMENTALDESIGN:
1,079 previously untreated patients with advanced NSCLC were enrolled and randomized in a phase III trial (TRIBUTE) to receive either erlotinib or placebo in combination with paclitaxel 200 mg/m2 IV over 3 h and carboplatin at a calculated dose to achieve an AUC 6 mgâmin/mL. To determine possible drug-drug interaction with this combination, a subset of 24 (12 erlotinib, 12 placebo) patients were enrolled onto an intensive pharmacokinetic (IPK) substudy group at a single site. All IPK patients received either erlotinib 150 mg/day or placebo-controlled tablets. Analyses were completed using validated analytical methodologies. Non-compartmental modeling was utilized to estimate PK parameters.RESULTS:
Complete blood sampling for pharmacokinetic analysis was obtained in 21 of 24 patients. Mean AUC(0-τ) for erlotinib and the OSI-420 metabolite were 29,997 ngâh/mL and 3,020 ngâh/mL, respectively. Mean (SD) paclitaxel clearances (L/h/M(2)) were 11.7 (3.4) and 12.7 (6.7) in the placebo and erlotinib treatment groups, respectively. The resultant paclitaxel AUC(0-∞) (ngâh/mL) was 18,400 (5,300) for the placebo group and 17,800 (5,500) for the erlotinib group. For carboplatin, the mean (SD) clearances (L/h) were 16.8 (3.9) and 16.1 (4.4) for the placebo and erlotinib groups, respectively. The resultant carboplatin AUC(0-∞) (ng/mLâh) were 49,900 (9,700) for the placebo group and 48,400 (11,900) for the erlotinib group. No significant differences were observed in these paclitaxel or carboplatin pharmacokinetic group comparisons.CONCLUSIONS:
The addition of erlotinib to a standard chemotherapy regimen for NSCLC did not alter the systemic exposures (AUC(0-∞)) of paclitaxel (p = 0.80) and carboplatin (p = 0.756) when erlotinib-treated patients were compared to placebo-treated patients. The pharmacokinetics of erlotinib and its metabolite OSI-420 did not appear to be altered by the concomitant administration of paclitaxel and carboplatin.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Quinazolinas
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Carboplatina
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Paclitaxel
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Carcinoma Pulmonar de Células não Pequenas
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Neoplasias Pulmonares
Tipo de estudo:
Clinical_trials
/
Prognostic_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:
2011
Tipo de documento:
Article