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Vinorelbine/docetaxel combination treatment of metastatic breast cancer: a phase I study

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Abstract

Purpose

The aim of this study was to investigate the combination of vinorelbine (VRL) alternating intravenous (i.v.) and oral in combination with docetaxel (DCT) as first-line chemotherapy of patients with metastatic breast cancer.

Patients and methods

Tested doses were 60 or 70 mg m−2 given on day 1 for DCT, 20 to 25 mg m−2 for i.v. VRL on day 1, 60 mg m−2 on day 8 or day 15 for oral VRL. Day 1 was administered every 3 weeks. Three to six patients were treated per dose level.

Results

The median age of the 30 treated patients was 60 years. Four patients were non evaluable for the maximum tolerated dose (MTD) and were replaced. Reported dose-limiting toxicities were 11 omissions of oral VRL for neutropenia, two cases of febrile neutropenia and two grade 4 neutropenia ≥7 days. Dose levels using DCT doses >60 mg m−2 and/or i.v. VRL doses >20 mg m−2 met the criteria for MTD. Most frequent toxicities were febrile neutropenia in seven patients and neutropenic infection in four patients (one fatal). Therefore, the recommended schedule was established at i.v. VRL 20 mg m−2 with DCT 60 mg m−2 on day 1 and oral VRL 60 mg m−2 given on day 15 every 3 weeks. At this recommended schedule, only one of six patients experienced febrile neutropenia. Among 22 patients evaluable for tumour response, 2 complete and 10 partial responses were reported. Pharmacokinetics of combined VRL and DCT demonstrated the absence of mutual interaction.

Conclusions

This phase I study established the recommended doses and schedules of the combination alternating i.v. and oral VRL with DCT, this recommended regimen being further explored in a phase II study.

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Acknowledgments

This study was supported by an unrestricted grant from Institut de Recherche Pierre Fabre, Boulogne, France.

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Authors and Affiliations

  1. Centre Oscar Lambret, 3, rue Frédéric Combemale, B.P. 307, Lille Cedex, 59020, France

    J. Bonneterre

  2. Centre René Gauducheau, Nantes, 44805, France

    M. Campone & R. Deporte-Fety

  3. Wojewodzki Szpital Specjalistyczny im. L. Rydygiera, Krakow, 31 826, Poland

    P. Koralewski

  4. Wojewodzki Szpital Specjalistyczny im. M. Kopernika, Lodz, 93 509, Poland

    M. Blasinska-Morawiec

  5. Institut Claudius Regaud, Toulouse, 31052, France

    E. Chatelut

  6. Institut de Recherche Pierre Fabre, Castres, 81106, France

    F. Leger

  7. Institut de Recherche Pierre Fabre, Boulogne, 92654, France

    B. Longerey, L. Ecochard & I. Douville

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  1. J. Bonneterre
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Correspondence to J. Bonneterre.

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Bonneterre, J., Campone, M., Koralewski, P. et al. Vinorelbine/docetaxel combination treatment of metastatic breast cancer: a phase I study. Cancer Chemother Pharmacol 60, 365–373 (2007). https://doi.org/10.1007/s00280-006-0375-6

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  • DOI: https://doi.org/10.1007/s00280-006-0375-6

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