How to manage intravenous vinflunine in cancer patients with renal impairment: Results of a pharmacokinetic and tolerability phase i study

Abstract

Aims Vinflunine (VFL) ditartrate, a novel tubulin-targeted inhibitor, is registered for the treatment of patients with advanced or metastatic urothelial transitional cell carcinoma. This phase I study assessed the effect of renal impairment on the pharmacokinetics and tolerability of VFL. Methods VFL was infused in patients with advanced/metastatic solid tumours once every 3 weeks with anticipated dose reduction on the first cycle stratified according to the creatinine clearance (CLcr) values. Pharmacokinetic data were collected on the first two cycles in renally impaired patients (CLcr ≤ 60 ml min-1) and were compared with a control cohort of patients (CLcr > 60 ml min-1). Results Thirty-three patients (46-86 years) were treated, 13 in group 1 (40 ml min-1 ≤ CL cr ≤ 60 ml min-1) and 20 in group 2 (20 ml min -1 ≤ CLcr < 40 ml min-1). The renal dysfunction induced a mean decrease in VFL clearance of 12% in group 1 and 28% in group 2, compared with the control group. The anticipated dose reduction given in renally impaired patients (i.e. 280 mg m-2 and 250 mg m -2 in groups 1 and 2, respectively) yielded similar drug exposure to control patients. The tolerance profile of VFL in patients with renal dysfunction was similar to that observed in patients with CLcr > 60 ml min-1. Conclusion In conclusion, the recommended doses of intravenous VFL administered once every 3 weeks in cancer patients with renal impairment are 280 mg m-2 when CLcr is between 40 and 60 ml min-1 and 250 mg m-2 when CLcr is between 20 and <40 ml min-1. © 2013 The British Pharmacological Society.