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How to manage intravenous vinflunine in cancer patients with renal impairment: results of a pharmacokinetic and tolerability phase I study
Author(s) -
Isambert Nicolas,
Delord Jean Pierre,
Tourani Jean Marc,
Fumoleau Pierre,
Ravaud Alain,
Pinel Marie Claire,
Petain Aurelie,
Nguyen Thierry,
Nguyen Laurent
Publication year - 2014
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12218
Subject(s) - tolerability , medicine , pharmacokinetics , urology , renal function , renal cell carcinoma , pharmacology , adverse effect
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 .