A phase I clinical and pharmacokinetic study evaluating vinflunine in combination with epirubicin as first-line treatment in metastatic breast cancer

Background Vinflunine (VFL) is a bifluorinated tubulin-targeted agent of the vinca alkaloids class active in advanced stage breast cancer. We conducted a phase I study combining VFL with epirubicin (EPR) to establish the recommended dose (RD), to evaluate the safety and efficacy profiles and to investigate potential pharmacokinetic (PK) drug–drug interaction (DDI). Patients and methods Two schedules (day 1 every 3 weeks; days 1 and 8 every 3 weeks) were investigated as first-line chemotherapy of metastatic breast cancer patient. PK DDI was evaluated through population PK approaches. Results Thirty-nine patients received a total of 197 cycles of the VFL–EPR combination (median 6). The RDs were VFL 250 mg/m 2 + EPR 75 mg/m 2 every 3 weeks for schedule 1 and VFL 170 mg/m 2 + EPR 35 mg/m 2 every 3 weeks for schedule 2. The PK analysis demonstrated no clinically relevant mutual DDI between VFL and EPR. The main dose-limiting toxicity was neutropenia. The most frequent non-haematological adverse events were nausea, fatigue, constipation, vomiting, anorexia and stomatitis. Objective response rate was achieved in 45.9 % of the patients. Conclusion VFL–EPR combination is feasible with manageable toxicity. The antitumour activity was promising and supports further evaluation.