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) .
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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)
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Copyright | © 2013 The British Pharmacological Society. |
Chemical References |
- Antineoplastic Agents, Phytogenic
- Tubulin Modulators
- vinflunine
- Vinblastine
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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)
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