A phase I pharmacokinetic and safety study of cabazitaxel in adult cancer patients with normal and impaired renal function.

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 m), B (moderate renal impairment: CrCL 30 to <50 mL/min/1.73 m) and C (severe impairment: CrCL <30 mL/min/1.73 m) received cabazitaxel 25 mg/m (A, B) or 20 mg/m (C, could be escalated to 25 mg/m), 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) versus a control (90 mL/min/1.73 m).

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 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.

Conclusions: Renal impairment had no clinically meaningful effect on cabazitaxel pharmacokinetics.