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Epirubicin and paclitaxel with G-CSF support in first line metastatic breast cancer: a randomized phase II study of dose-dense and dose-escalated chemotherapy

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Abstract

An increased dose-intensity can be achieved by either higher dose of chemotherapy per cycle (dose-escalation) or by shortening the interval between cycles (dose-dense). This multicenter randomized phase II study assessed the efficacy and safety of two different approaches: epirubicin 110 mg/m2 combined with paclitaxel 200 mg/m2 every 21 days and epirubicin 75 mg/m2 combined with paclitaxel 175 mg/m2 every 10 days, both supported with G-CSF. Patients with advanced breast cancer and without prior palliative chemotherapy were scheduled for 6 cycles. Evaluable for response were 101 patients and for toxicity 106 patients. Grade ≥3 toxicities occurred in 39% of patients in the dose-escalated arm and in 29% of the dose-dense arm, mainly febrile neutropenia, thrombocytopenia, neurotoxicity and (asymptomatic) cardiotoxicity. The median delivered cumulative doses for epirubicin/paclitaxel were 656/1194 and 448/1045 mg/m2, treatment durations were 126 and 61 days, and delivered dose intensities were 36/67 and 51/120 mg/m2/week for the dose-escalated and dose-dense arm, respectively. Response rates were 75 and 70%, the progression-free survival 6 and 7 months, respectively. Dose-dense chemotherapy with a lower cumulative dose, a halved treatment time, but a higher dose-intensity may be as effective and safe as dose-escalated chemotherapy. The value of dose-densification over standard scheduled chemotherapy regimes yet needs to be determined.

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Acknowledgments

This work was supported in part by grants from Amgen Inc., Pfizer Inc. and Bristol-Myers Squibb Inc.

Conflict of interest

The authors declare that they have no actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations within that could inappropriately influence (bias) their work.

Author information

Author notes

  1. C. T. A. M. Knibbeler-van Rossum

    Present address: Jeroen Bosch Ziekenhuis, Den Bosch, The Netherlands

  2. J. W. R. Nortier

    Present address: Leids Universitair Medisch Centrum, Leiden, The Netherlands

Authors and Affiliations

  1. Division of Medical Oncology, Department of Internal Medicine, GROW-School of Oncology and Developmental Biology, Maastricht Universitair Medisch Centrum, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands

    R. I. Lalisang & V. C. G. Tjan-Heijnen

  2. Orbis Medisch Centrum, Sittard, The Netherlands

    F. L. G. Erdkamp

  3. Meander Medisch Centrum, Amersfoort, The Netherlands

    C. J. Rodenburg

  4. St. Elisabeth Ziekenhuis, Tilburg, The Netherlands

    C. T. A. M. Knibbeler-van Rossum

  5. Diaconessenhuis, Utrecht, The Netherlands

    J. W. R. Nortier

  6. Zaans Medisch Centrum, Zaandam, The Netherlands

    A. van Bochove

  7. St. Antonius Ziekenhuis, Nieuwegein, The Netherlands

    P. H. Th. J. Slee

  8. Universitair Medisch Centrum Utrecht, Utrecht, The Netherlands

    E. E. Voest & G. H. Blijham

  9. Laurentius Ziekenhuis, Roermond, The Netherlands

    J. A. Wils

  10. Atrium Medisch Centrum, Heerlen, The Netherlands

    J. Wals

  11. Amphia Ziekenhuis, Breda, The Netherlands

    O. J. L. Loosveld

  12. St. Anna Ziekenhuis, Geldrop, The Netherlands

    A. E. M. Smals

  13. Division of Hematology, Department of Internal Medicine, GROW-School of Oncology and Developmental Biology, Maastricht Universitair Medisch Centrum, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands

    H. C. Schouten

Authors
  1. R. I. Lalisang
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  2. F. L. G. Erdkamp
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  4. C. T. A. M. Knibbeler-van Rossum
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  6. A. van Bochove
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  7. P. H. Th. J. Slee
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  8. E. E. Voest
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  9. J. A. Wils
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  10. J. Wals
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  11. O. J. L. Loosveld
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  12. A. E. M. Smals
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  13. G. H. Blijham
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  14. V. C. G. Tjan-Heijnen
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Corresponding author

Correspondence to R. I. Lalisang.

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Lalisang, R.I., Erdkamp, F.L.G., Rodenburg, C.J. et al. Epirubicin and paclitaxel with G-CSF support in first line metastatic breast cancer: a randomized phase II study of dose-dense and dose-escalated chemotherapy. Breast Cancer Res Treat 128, 437–445 (2011). https://doi.org/10.1007/s10549-011-1558-3

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  • DOI: https://doi.org/10.1007/s10549-011-1558-3

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