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

AimsVinflunine (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. MethodsVFL 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 60mlmin(-1)) and were compared with a control cohort of patients (CLcr > 60mlmin(-1)). ResultsThirty-three patients (46-86 years) were treated, 13 in group 1 (40mlmin(-1) CLcr 60mlmin(-1)) and 20 in group 2 (20mlmin(-1) CLcr < 40mlmin(-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. 280mgm(-2) and 250mgm(-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 > 60mlmin(-1). ConclusionIn conclusion, the recommended doses of intravenous VFL administered once every 3 weeks in cancer patients with renal impairment are 280mgm(-2) when CLcr is between 40 and 60mlmin(-1) and 250mgm(-2) when CLcr is between 20 and <40mlmin(-1).