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Taxanes Alone or in Combination With Anthracyclines As First-Line Therapy of Patients With Metastatic Breast Cancer

Martine J. Piccart-Gebhart, Tomasz Burzykowski, Marc Buyse, George Sledge, James Carmichael, Hans-Joachim Lück, John R. Mackey, Jean-Marc Nabholtz, Robert Paridaens, Laura Biganzoli, Jacek Jassem, Marijke Bontenbal, Jacques Bonneterre, Stephen Chan, Gul Atalay Basaran, Patrick Therasse

From the Institut Jules Bordet; European Organization for Research and Treatment of Cancer, Brussels; Hasselt University, Diepenbeek; International Drug Development Institute, Louvain-la-Neuve; University Hospital Gasthuisberg, Leuven, Belgium; Indiana University-Purdue University, Indianapolis, IN; Astra-zeneca, Macclesfield; Nottingham City Hospital, Nottingham, United Kingdom; Medizinische Hochschule, Hannover, Germany; University of Alberta, Edmonton, Alberta, Canada; Breast Cancer Research Institute-La Prandie, Valojoulx; Centre Oscar Lambret, Lille, France; Hospital of Prato, Prato, Italy; Medical University of Gdask, Gdask, Poland; Erasmus MC, University Medical Center, Rotterdam, the Netherlands; and Marmara University Hospital, Istanbul, Turkey

Corresponding author: Martine J. Piccart-Gebhart, MD, PhD, Institut Jules Bordet, 121 boulevard de Waterloo, 1000 Brussels, Belgium; e-mail: martine.piccart{at}bordet.be

Purpose: Taxanes (paclitaxel or docetaxel) have been sequenced or combined with anthracyclines (doxorubicin or epirubicin) for the first-line treatment of advanced breast cancer. This meta-analysis uses data from all relevant trials to detect any advantages of taxanes in terms of tumor response, progression-free survival (PFS), and survival.

Patients and Methods: Individual patient data were collected on eight randomized combination trials comparing anthracyclines + taxanes (+ cyclophosphamide in one trial) with anthracyclines + cyclophosphamide (+ fluorouracil in four trials), and on three single-agent trials comparing taxanes with anthracyclines. Combination trials included 3,034 patients; single-agent trials included 919 patients.

Results: Median follow-up of living patients was 43 months, median survival was 19.3 months, and median PFS was 7.1 months. In single-agent trials, response rates were similar in the taxanes (38%) and in the anthracyclines (33%) arms (P = .08). The hazard ratios for taxanes compared with anthracyclines were 1.19 (95% CI, 1.04 to 1.36; P = .011) for PFS and 1.01 (95% CI, 0.88 to 1.16; P = .90) for survival. In combination trials, response rates were 57% (10% complete) in taxane-based combinations and 46% (6% complete) in control arms (P < .001). The hazard ratios for taxane-based combinations compared with control arms were 0.92 (95% CI, 0.85 to 0.99; P = .031) for PFS and 0.95 (95% CI, 0.88 to 1.03; P = .24) for survival.

Conclusion: Taxanes were significantly worse than single-agent anthracyclines in terms of PFS, but not in terms of response rates or survival. Taxane-based combinations were significantly better than anthracycline-based combinations in terms of response rates and PFS, but not in terms of survival.

Supported by the IAP research network P6/03 of the Belgian government (T.B.). No financial support was sought from any of the trial sponsors.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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				T. Burzykowski, M. Buyse, M. J. Piccart-Gebhart, G. Sledge, J. Carmichael, H.-J. Luck, J. R. Mackey, J.-M. Nabholtz, R. Paridaens, L. Biganzoli, et al. Evaluation of Tumor Response, Disease Control, Progression-Free Survival, and Time to Progression As Potential Surrogate End Points in Metastatic Breast Cancer J. Clin. Oncol., April 20, 2008; 26(12): 1987 - 1992. [Abstract] [Full Text] [PDF]