A phase I pharmacokinetic and safety study of cabazitaxel in adult cancer patients with normal and impaired renal function.
Cancer Chemother Pharmacol
; 78(6): 1185-1197, 2016 Dec.
Article
em En
| MEDLINE
| ID: mdl-27796539
ABSTRACT
PURPOSE:
Limited data are available on cabazitaxel pharmacokinetics in patients with renal impairment. This open-label, multicenter study assessed cabazitaxel in patients with advanced solid tumors and normal or impaired renal function.METHODS:
Cohorts A (normal renal function creatinine clearance [CrCL] >80 mL/min/1.73 m2), B (moderate renal impairment CrCL 30 to <50 mL/min/1.73 m2) and C (severe impairment CrCL <30 mL/min/1.73 m2) received cabazitaxel 25 mg/m2 (A, B) or 20 mg/m2 (C, could be escalated to 25 mg/m2), once every 3 weeks. Pharmacokinetic parameters and cabazitaxel unbound fraction (F U) were assessed using linear regression and mixed models. Geometric mean (GM) and GM ratios (GMRs) were determined using mean CrCL intervals (moderate and severe renal impairment 40 and 15 mL/min/1.73 m2) versus a control (90 mL/min/1.73 m2).RESULTS:
Overall, 25 patients received cabazitaxel (median cycles 3 [range 1-20]; Cohort A 5 [2-13]; Cohort B 3 [1-15]; and Cohort C 5 [1-20]), of which 24 were eligible for pharmacokinetic analysis (eight in each cohort). For moderate and severe renal impairment versus normal renal function, GMR estimates were clearance normalized to body surface area (CL/BSA) 0.95 (90% CI 0.80-1.13) and 0.89 (0.61-1.32); area under the curve normalized to dose (AUC/dose) 1.06 (0.88-1.27) and 1.14 (0.76-1.71); and F U 0.99 (0.94-1.04) and 0.97 (0.87-1.09), respectively. Estimated slopes of linear regression of log parameters versus log CrCL (renal impairment) were CL/BSA 0.06 (-0.15 to 0.28); AUC/dose -0.07 (-0.30 to 0.16); and F U 0.02 (-0.05 to 0.08). Cabazitaxel safety profile was consistent with previous reports.CONCLUSIONS:
Renal impairment had no clinically meaningful effect on cabazitaxel pharmacokinetics.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Taxoides
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Insuficiência Renal
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Neoplasias
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Antineoplásicos
Tipo de estudo:
Clinical_trials
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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:
2016
Tipo de documento:
Article