title: How to manage intravenous vinflunine in cancer patients with renal impairment: results of a pharmacokinetic and tolerability phase I study.
abstract: OBJECTIVE
  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) .
  
  
  CONCLUSIONS
  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.affiliation: Medical Oncology, Centre G.F. Leclerc, Dijon, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Isambert
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Delord
authors.forename: Jean Marc
authors.initials: JM
authors.lastname: Tourani
authors.forename: Pierre
authors.initials: P
authors.lastname: Fumoleau
authors.forename: Alain
authors.initials: A
authors.lastname: Ravaud
authors.forename: Marie Claire
authors.initials: MC
authors.lastname: Pinel
authors.forename: Aurelie
authors.initials: A
authors.lastname: Petain
authors.forename: Thierry
authors.initials: T
authors.lastname: Nguyen
authors.forename: Laurent
authors.initials: L
authors.lastname: Nguyen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D005260:Female; D005602:France; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000503:physiopathology*; D007674:Kidney Diseases / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome; D050257:Tubulin Modulators / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D050257:Tubulin Modulators; C111217:vinflunine; D014747:Vinblastine
keywords: advanced/metastatic solid tumours; pharmacokinetics; phase I; renal impairment; vinflunine