Individually tailored treatment with epirubicin and paclitaxel with or without capecitabine as first-line chemotherapy in metastatic breast cancer: a randomized multicenter trial


Anthracyclines and taxanes are active cytotoxic drugs in the treatment of early metastatic breast cancer. It is yet unclear whether addition of capecitabine to the combination of these drugs improves the treatment outcome. Patients with advanced breast cancer were randomized to first-line chemotherapy with a combination of epirubicin (Farmorubicin®) and paclitaxel (Taxol®) alone (ET) or in combination with capecitabine (Xeloda®, TEX). Starting doses for ET were epirubicin 75 mg/m2 plus paclitaxel 175 mg/m2, and for TEX epirubicin 75 mg/m2, paclitaxel 155 mg/m2, and capecitabine 825 mg/m2 BID for 14 days. Subsequently, doses were tailored related to side effects. Primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), time to treatment failure (TTF), objective response (OR), safety and quality of life (QoL). 287 patients were randomized, 143 to ET and 144 to TEX. Median PFS was 10.8 months for patients treated with ET, and 12.4 months for those treated with TEX (HR 0.84, 95% CI 0.65–1.07, P = 0.16); median OS was 26.0 months for women in the ET versus 29.7 months in the TEX arm (HR 0.84, 95% CI 0.63–1.11, P = 0.22). OR was achieved in 44.8% (ET) and 54.2% (TEX), respectively (χ2 3.66, P = 0.16). TTF was significantly longer for patients treated with TEX, 6.0 months, versus 5.2 months following ET (HR 0.73, 95% CI 0.58–0.93, P = 0.009). Severe hematological side effects related to epirubicin and paclitaxel were evenly distributed between the treatment arms, mucositis, diarrhea, and Hand-Foot syndrome were significantly more frequent in the TEX arm. Toxicity-adjusted treatment with ET and TEX showed similar efficacy in terms of PFS, OS, and OR. In this trial with limited power, the addition of capecitabine to epirubicin and paclitaxel as first-line treatment did not translate into clinically relevant improvement of the outcome.

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Members of the Independent Review Committee Prof. Lars Holmberg, Division of Cancer Studies, King’s College, London, UK, Assoc. Prof. Torgil Möller, Dept of Cancer Epidemiology, Lund University, Sweden, and Prof. Erik Wist, Oslo University Hospital, Oslo, Norway, for constructive discussions during the study.


Unrestricted grants from Bristol-Myers Squibb Sweden AB, Pfizer Sweden AB and Roche Sweden AB, the Research Funds at Radiumhemmet, the Swedish Cancer Society, the Swedish Breast Cancer Association (BRO) and ALF/FOU research funds at the Karolinska Institutet and Stockholm County Council.

Conflict of interest

T. Hatschek: Consulting/advisory role: Pfizer; Funding: Roche, Sanofi-aventis. L. Carlsson: None. Z. Einbeigi: None. E. Lidbrink: None. B. Linderholm: None. B. Lindh: None. N. Loman: None. M. Malmberg: None. S. Rotstein: None. M. Söderberg: Consultant/advisory role: BMS, Roche. M. Sundquist: None. T. M. Walz: None. M. Hellström: None. K. Hammarlund: None. H. Svensson: None. G. Åström: None. Y. Brandberg: None. J. Carstensen: None. M. Fernö: None. J. Bergh: Consultant/advisory role: Amgen, Astrazeneca, GlaxoSmithKline, Pfizer, Sanofi-aventis; Funding: Amgen, Merck, Sanofi-aventis.

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Corresponding author

Correspondence to T. Hatschek.

Additional information

This study was conducted on behalf of TEX study group.

Participating investigators of the TEX study group are given in Appendix.



Participating investigators of the TEX study group

Coordinating Investigator: Thomas Hatschek, Translational research: Mårten Fernö, QoL: Yvonne Brandberg, Statistics: John Carstensen, Laboratory: Suzanne Egyhazy, Marianne Frostvik Stolt, Lambert Skogh, Clinical Trial Office: Mats Hellström, Maarit Maliniemi, Helene Svensson, Radiology: Gunnar Åström, Departments of Oncology at 1. Karolinska University Hospital, Stockholm: Jonas Bergh, Judith Bjöhle, Elisabet Lidbrink, Sam Rotstein, Birgitta Wallberg, 2. Sahlgrenska University Hospital, Gothenburg: Zakaria Einbeigi, Per Carlsson, Barbro Linderholm, 3. Linköping University Hospital: Thomas M Walz, 4. Skåne University Hospital Malmö: Martin Söderberg, 5. Skåne University Hospital Lund: Niklas Loman, Per Malmström, 6. Helsingborg General Hospital: Martin Malmberg, 7. Sundsvall General Hospital: Lena Carlsson, 8. Umeå University Hospital: Birgitta Lindh, 9. Kalmar General Hospital: Marie Sundqvist, 10. Karlstad General Hospital: Lena Malmberg.

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Hatschek, T., Carlsson, L., Einbeigi, Z. et al. Individually tailored treatment with epirubicin and paclitaxel with or without capecitabine as first-line chemotherapy in metastatic breast cancer: a randomized multicenter trial. Breast Cancer Res Treat 131, 939–947 (2012).

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  • Advanced breast cancer
  • First-line treatment
  • Epirubicin
  • Paclitaxel
  • Capecitabine