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) ≤ 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) .

• Authors: Nicolas Isambert, Jean Pierre Delord, Jean Marc Tourani, Pierre Fumoleau, Alain Ravaud, Marie Claire Pinel, Aurelie Petain, Thierry Nguyen, Laurent Nguyen
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 77 Issue 3 Pg. 498-508 (Mar 2014) ISSN: 1365-2125 [Electronic] England
• PMID: 24283925 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study)
• Copyright: © 2013 The British Pharmacological Society.

Chemical References

• Antineoplastic Agents, Phytogenic
• Tubulin Modulators
• vinflunine
• Vinblastine

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Agents, Phytogenic (administration & dosage, adverse effects, pharmacokinetics)
• Drug Administration Schedule
• Female
• France
• Humans
• Infusions, Intravenous
• Kidney (physiopathology)
• Kidney Diseases (complications, diagnosis, physiopathology)
• Male
• Metabolic Clearance Rate
• Middle Aged
• Neoplasms (complications, diagnosis, drug therapy)
• Treatment Outcome
• Tubulin Modulators (administration & dosage, adverse effects, pharmacokinetics)
• Vinblastine (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics)