A phase I clinical and pharmacological study evaluating vinflunine in combination with doxorubicin as first line treatment in metastatic breast cancer
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- Zaman, K., Durando, X., Baurain, JF. et al. Breast Cancer Res Treat (2011) 127: 689. doi:10.1007/s10549-011-1446-x
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Vinfunine (VFL) is a novel bifluorinated tubulin-targeted agent of the vinca alkaloids class active in advanced stage breast cancer. We conducted a phase I study combining VFL with doxorubicin (DXR) to define the recommended dose (RD), safety, pharmacokinetic (PK) interaction and efficacy. Two schedules (day 1 every 3 weeks; days 1 and 8 every 3 weeks) were investigated as first line chemotherapy in metastatic breast cancer patients. Thirty-two patients received a total of 162 cycles of the VFL–DXR combination (median 6). The RDs were VFL 250 mg/m2/DXR 40 mg/m2 every 3 weeks for schedule 1 and VFL 120 mg/m2/DXR 25 mg/m2 days 1 and 8 every 3 weeks for schedule 2. The main dose-limiting toxicity was neutropenia. The most frequent non-hematological adverse events were nausea, fatigue, constipation, vomiting, anorexia, stomatitis and dyspnea. Objective response rate was reached in 47.1% of the patients. No PK interaction was observed. VFL–DXR combination is feasible with manageable toxicity. The antitumor activity was promising and supports further evaluation.