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

作者：Chan S^*; Campone M; Santoro A; Conte P F; Bostnavaron M; Nguyen L

来源：Cancer Chemotherapy and Pharmacology, 2014, 73(5): 903-910.

DOI：10.1007/s00280-014-2420-1

• Vinflunine
• Epirubicin
• MBC
• Phase 1
• First line

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). %26lt;br%26gt;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. %26lt;br%26gt;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. %26lt;br%26gt;VFL-EPR combination is feasible with manageable toxicity. The antitumour activity was promising and supports further evaluation.

• 出版日期2014-5