Phase I and Pharmacokinetic Study of IV Vinflunine in Combination with Gemcitabine for Treatment of Advanced Non-small Cell Lung Cancer in Chemonaive Patients

Introduction: Vinflunine (Javlor) has shown significant antitumour activity in advanced non-small cell lung cancer (NSCLC). We propose to define the recommended dose of vinflunine in combination with gemcitabine for treatment of advanced NSCLC in chemonaive patients. Methods: A phase I and pharmacokinetic study was conducted to determine the maximum tolerated dose and to establish the recommended dose of vinflunine (VFL) administered on day 1 every 21 days combined with gemcitabine given on days 1 and 8 every 3 weeks. Results: Nineteen patients were included in this study. Three patients experienced a dose limiting toxicity, with constipation in one patient, hypertension in one patient, and constipation and febrile neutropenia in one patient. The combination of VFL 320 mg/m(2) and gemcitabine 1250 mg/m(2) was defined as the maximum tolerated dose. The recommended dose was established at the dose of VFL 320 mg/m(2) combined with gemcitabine 1000 mg/m(2). Neither VFL nor gemcitabine seemed to be influencing the pharmacokinetics of each other. All patients were evaluable for tumor response. Seven presented a partial response and eight experienced a stable disease. Conclusions: The combination of VFL 320 mg/m(2) administered on day 1 combined with gemcitabine 1000 mg/m(2) given on days 1 and 8 every 3 weeks is established as the RD and was shown to be active in these chemonaive NSCLC patients.