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) ≤ CLcr ≤ 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) .
Keywords: advanced/metastatic solid tumours; pharmacokinetics; phase I; renal impairment; vinflunine.
© 2013 The British Pharmacological Society.