A GINECO randomized phase II trial of two capecitabine and weekly paclitaxel schedules in metastatic breast cancer

Abstract

To determine whether capecitabine schedule adaptation improves the tolerability of capecitabine–paclitaxel combination therapy for metastatic breast cancer (MBC), patients with anthracycline-pretreated HER2-negative MBC were randomized to either arm A (21-day cycles: capecitabine 1,000 mg/m2 twice daily, days 1–14; paclitaxel 60 mg/m2, days 1, 8, and 15) or arm B (28-day cycles: capecitabine 1,000 mg/m2 twice daily, days 1–5, 8–12, and 15–19; paclitaxel 80 mg/m2, days 1, 8, and 15). The primary endpoint was the incidence of dose reductions or delays >1 week for grade 3/4 toxicity. Secondary endpoints were efficacy and safety. All 130 randomized patients were evaluable for safety. Dose reduction or delay for grade 3/4 toxicity occurred in 39% of patients in arm A and 34% in arm B during cycles 1–6. In arm A, there were significantly more toxicity-related dose reductions (cycles 1–6: 82 vs. 67%, respectively; P = 0.05) and discontinuations (29 vs. 8%, respectively). Grade 3 diarrhea occurred in 12 and 0%, respectively, and grade 3 hand-foot syndrome in 12 versus 9%, respectively (grade 4 not applicable). There were no detectable differences in efficacy. Weekday capecitabine dosing with weekly paclitaxel may improve tolerability without a detrimental effect on efficacy, and merits further evaluation in patients suited to combination chemotherapy.

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Acknowledgments

The authors would like to thank Nicolas Gane, Data Management at the study office of ARCAGY-GINECO (the sponsor of the study), Paris. We also thank the following investigators who participated in the trial: Dr P.L. Etienne (Clinique Armoricaine de Radiologie, Saint Brieuc); Dr P. Dalivoust (Hôpital Saint-Joseph, Marseille); Dr C. El Kouri and Dr J.F. Ramee (Centre Catherine de Sienne, Nantes); Dr J.M. Ferrero and Dr W. Lescaut (Centre Antoine Lacassagne, Nice); Dr J.P. Guastalla and Dr I. Ray-Coquard (Centre Léon Bérard, Lyon); Dr S. Kirscher (Institut Sainte Catherine, Avignon); Dr L. Chauvenet (Hôpital Hôtel-Dieu, Paris); and Dr G. Sadki-Benaoudia (Centre Hospitalier Robert Ballanger, Aulnay sous Bois). This work and third-party medical writing assistance for this article were supported by Roche France.

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The authors declared no conflict of interest.

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Correspondence to Alain Lortholary.

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This study was conducted on behalf of the GINECO Group.

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Lortholary, A., Hardy-Bessard, AC., Bachelot, T. et al. A GINECO randomized phase II trial of two capecitabine and weekly paclitaxel schedules in metastatic breast cancer. Breast Cancer Res Treat 131, 127–135 (2012). https://doi.org/10.1007/s10549-011-1776-8

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Keywords

  • Capecitabine
  • Combination therapy
  • Metastatic breast cancer
  • Weekly paclitaxel