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Capecitabine plus paclitaxel versus epirubicin plus paclitaxel as first-line treatment for metastatic breast cancer: efficacy and safety results of a randomized, phase III trial by the AGO Breast Cancer Study Group

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Abstract

Capecitabine/taxane combinations are highly active in metastatic breast cancer (MBC). We conducted a randomized, phase III, noninferiority trial comparing capecitabine plus paclitaxel (XP) with epirubicin plus paclitaxel (EP) as first-line therapy for MBC, regarding progression-free survival (PFS) as primary efficacy endpoint. Females who had received no prior chemotherapy for MBC were randomized to six 3-weekly cycles of XP (capecitabine 1000 mg/m2 b.i.d., days 1–14; paclitaxel 175 mg/m2 3-h infusion, day 1) or EP (epirubicin 60 mg/m2 1-h infusion, day 1; paclitaxel as above). Secondary endpoints included response rate, overall survival, tolerability, and quality of life (QoL). Each arm included 170 patients, most of whom received all six cycles as planned. The difference in means of (logarithmic) PFS times (−0.205) did not meet the pre-defined level for noninferiority (−0.186). However, PFS was similar in the two arms [HR: XP vs. EP: 1.012 (95 % CI 0.785–1.304); median 10.4 months XP vs. 9.2 months EP]. Overall survival was also similar [HR 1.027 (95 % CI 0.740–1.424); median 22.0 vs. 26.1 months], and response rate was 47 % versus 42 %. Both regimens were tolerable: there were more grade 3/4 diarrhea and grade 3 hand–foot syndromes with XP and more grade 3/4 hematologic toxicities with EP. There were no major differences in QoL. Although, noninferiority of XP to EP was formally not proven, first-line XP was active and feasible. XP is a valid first-line alternative to anthracycline/taxane regimens, especially in patients previously treated with adjuvant anthracyclines.

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Acknowledgments

The authors would like to acknowledge the work of our advisory board, consisting of the following persons: Prof Dr G Emons, Prof Dr F Jänicke, Prof Dr M Kaufmann, Prof Dr H Kühnle, Prof Dr H-G Meerpohl (advisory board), and AGO principal investigators Dr B. Brückner, Dr H. Eidtmann, Prof Dr V Möbus, Prof Dr W Schröder, Prof Dr C Thomssen, Prof. Dr M Untch, Dr T Volm. This study is sponsored by the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) metastatic breast cancer study group. Financial support is provided by F. Hoffmann-La Roche and Bristol-Myers Squibb.

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Authors and Affiliations

  1. Dr. Horst Schmidt Klinik, Wiesbaden, Germany

    Hans-Joachim Lück & Andreas Du Bois

  2. German Breast Group, Martin-Behaim-Str. 12, 63263, Neu-Isenburg, Germany

    Sibylle Loibl & Gunter von Minckwitz

  3. Henriettenstiftung, Hannover, Germany

    Iris Schrader

  4. University Women’s Hospital, Tubingen, Germany

    Jens Huober

  5. University Women’s Hospital, Ulm, Germany

    Volker Heilmann

  6. University Women’s Hospital, Erlangen, Germany

    Matthias Beckmann

  7. St. Vincentius-Kliniken, Karlsruhe, Germany

    Ann Stähler

  8. University Women’s Hospital, Marburg, Germany

    Christian Jackisch

  9. University Women’s Hospital, Innsbruck, Austria

    Michael Hubalek

  10. University Women’s Hospital, Dresden, Germany

    Barbara Richter

  11. University Womens’Hospital, Freiburg, Germany

    Elmar Stickeler

  12. University Womens’ Hospital, Kiel, Germany

    Holger Eidtmann

  13. University Women’s Hospital, Hamburg/Halle, Germany

    Christoph Thomssen

  14. Helios Klinikum, Berlin Buch, Germany

    Michael Untch

  15. University Womens’Hospital, Magdeburg, Germany

    Kerstin Wollschläger

  16. Technische Universitaet, Munich, Germany

    Tibor Schuster

  17. University Women’s Hospital, Frankfurt, Germany

    Gunter von Minckwitz

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  1. Hans-Joachim Lück
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Correspondence to Gunter von Minckwitz.

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Lück, HJ., Du Bois, A., Loibl, S. et al. Capecitabine plus paclitaxel versus epirubicin plus paclitaxel as first-line treatment for metastatic breast cancer: efficacy and safety results of a randomized, phase III trial by the AGO Breast Cancer Study Group. Breast Cancer Res Treat 139, 779–787 (2013). https://doi.org/10.1007/s10549-013-2589-8

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