A phase I pharmacokinetic and safety study of cabazitaxel in adult cancer patients with normal and impaired renal function
Azaro, Analía (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)
Rodón, Jordi (Hospital Universitari Vall d'Hebron)
Machiels, Jean-Pascal (Institut Roi Albert II (Bèlgica). Department of Medical Oncology)
Rottey, Sylvie (Universitair Ziekenhuis Gent)
Damian, Silvia (National Cancer Institute of Milan)
Baird, Richard (Early Phase Clinical Trials Team, Department of Oncology, University of Cambridge, Cambridge, UK)
Garcia-Corbacho, Javier (Early Phase Clinical Trials Team, Department of Oncology, University of Cambridge, Cambridge, UK)
Mathijssen, Ron H. J. (Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands)
Clot, Pierre-François (Sanofi, Chilly-Mazarin, France)
Wack, Claudine (Sanofi, Chilly-Mazarin, France)
Shen, Liji (Sanofi, Bridgewater, NJ USA)
de Jonge, Maja (Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands)

Data:	2016
Resum:	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. Cohorts A (normal renal function: creatinine clearance [CrCL] >80 mL/min/1. 73 m 2), B (moderate renal impairment: CrCL 30 to <50 mL/min/1. 73 m 2) and C (severe impairment: CrCL <30 mL/min/1. 73 m 2) received cabazitaxel 25 mg/m 2 (A, B) or 20 mg/m 2 (C, could be escalated to 25 mg/m 2), once every 3 weeks. Pharmacokinetic parameters and cabazitaxel unbound fraction (F ) 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 m 2) versus a control (90 mL/min/1. 73 m 2). 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 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 0. 02 (−0. 05 to 0. 08). Cabazitaxel safety profile was consistent with previous reports. Renal impairment had no clinically meaningful effect on cabazitaxel pharmacokinetics.
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Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Cabazitaxel ; Renal impairment ; Pharmacokinetics ; Phase I ; Advanced solid tumors
Publicat a:	Cancer Chemotherapy and Pharmacology, Vol. 78 (october 2016) , p. 1185-1197, ISSN 1432-0843

DOI: 10.1007/s00280-016-3175-7
PMID: 27796539

13 p, 501.3 KB

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