A phase I, dose-escalation study of weekly vinflunine in patients with advanced solid tumours

Introduction: We aimed to investigate the dose-limiting toxicity and to determine the maximum tolerated dose of vinflunine (Javlor®, Pierre Fabre, Castres, France) given by weekly intravenous infusions for at least four consecutive weeks in patients with advanced solid tumours and to explore the pharmacokinetic profile of the drug when given in this schedule. Materials and methods: Thirty-nine patients, 14 previously treated by chemotherapy and 25 chemonaïve, received at least four weekly administrations of vinflunine over three and five dose levels (190-150-120 mg/m2 and 150-170-190-210-250 mg/m2, respectively). Vinflunine blood concentrations were quantified by high-performance liquid chromatography. Results: The dose-limiting toxicities with this dose schedule were primarily of haematologic origin (two cases of neutropenia and three cases of febrile neutropenia), with only two cases of non-haematologic dose-limiting toxicity (pneumonia and transaminase increase). Doses of 120 mg/m2 and 150 mg/m2 could be safely given on a weekly schedule over four and even six consecutive administrations. Predictable and reproducible pharmacokinetic behaviours were illustrated over successive weekly administrations. No pharmacokinetic difference was observed between pretreated and chemonaïve patients. Conclusions: The recommended doses for further clinical studies using vinflunine on a weekly administration schedule are 120 mg/m2 for pretreated patients and 150 mg/m2 for chemonaïve patients.