Breast Cancer Research and Treatment

, Volume 127, Issue 3, pp 689–696

A phase I clinical and pharmacological study evaluating vinflunine in combination with doxorubicin as first line treatment in metastatic breast cancer

  • K. Zaman
  • X. Durando
  • J.-F. Baurain
  • Y. Humblet
  • F. Mazzeo
  • M. Bostnavaron
  • N. Meheust
  • S. Monnoyer-Favrel
  • J.-P. Machiels
  • J. Bauer
Clinical trial

DOI: 10.1007/s10549-011-1446-x

Cite this article as:
Zaman, K., Durando, X., Baurain, JF. et al. Breast Cancer Res Treat (2011) 127: 689. doi:10.1007/s10549-011-1446-x

Abstract

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.

Keywords

Breast cancer Advanced stage Vinflunine Doxorubicin Phase I Pharmacokinetics 

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • K. Zaman
    • 1
  • X. Durando
    • 2
  • J.-F. Baurain
    • 3
  • Y. Humblet
    • 3
  • F. Mazzeo
    • 3
  • M. Bostnavaron
    • 4
  • N. Meheust
    • 4
  • S. Monnoyer-Favrel
    • 4
  • J.-P. Machiels
    • 3
  • J. Bauer
    • 1
  1. 1.Breast Center (CePO)University Hospital CHUVLausanneSwitzerland
  2. 2.Centre Jean PerrinClermont-FerrandFrance
  3. 3.Department of Medical Oncology Cliniques universitaires Saint-LucUniversité catholique de LouvainBrusselsBelgium
  4. 4.Institut de Recherche Pierre FabreBoulogne-BillancourtFrance