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

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 ( CL cr ) values. Pharmacokinetic data were collected on the first two cycles in renally impaired patients ( CL cr ≤ 60 ml min −1 ) and were compared with a control cohort of patients ( CL cr > 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 ≤ CL cr < 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 CL cr > 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 CL cr is between 40 and 60 ml min −1 and 250 mg m −2 when CL cr is between 20 and <40 ml min −1 .