INFLUENCE OF AGE ON THE PHARMACOKINETIC OF IV VINFLUNINE: RESULTS OF A PHASE I TRIAL IN ELDERLY CANCER PATIENTS

Objective: Vinflunine (VFL) is a novel microtubule inhibitor indicated in the treatment of advanced or metastatic urothelial transitional cell cancer after failure of a prior platinum-containing regimen at the recommended dose of 320 mg/m(2) q3 weeks. This trial was designed to assess the pharmacokinetic (PK) behavior and tolerance of VFL in elderly patients (pts), and to propose dose-adjustments if necessary. Material and methods: Three groups of cancer pts over 70 years old (y) were open to recruitment: 70-75 y, 75-80 y and >= 80 y. Each group of pts received intravenous VFL, respectively at 320, 280 and 250 mg/m2 on cycle 1. Pharmacokinetics and safety data were collected at cycle 1 and were compared to reference values from younger pts <70 y. Results: 46 pts were treated. For pts 70-75 y and 75-80 y, there was no statistically age-related change for VFL PK. For pts >= 80 y, VFL blood total clearance (Cl-tot) was significantly decreased by 18%. The most common adverse events observed in this elderly population were not different from those seen in younger pts. No toxic death was recorded. Main toxicities were neutropenia (Grade 3/4: 73% of pts), constipation (all grade: 63%) and asthenia (all grade: 56%), without any relationship between the observed incidence and the ageing of pts. Conclusion: Based on PK and safety data, a dose reduction at 280 mg/m(2) and 250 mg/m(2) is recommended in pts 75-80 y and >= 80 y respectively. (C) 2011 Elsevier Ltd. All rights reserved.