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Originally published as JCO Early Release 10.1200/JCO.2005.06.150 on August 8 2005

Journal of Clinical Oncology, Vol 23, No 25 (September 1), 2005: pp. 5960-5972
© 2005 American Society of Clinical Oncology.
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Maintaining Normal Hemoglobin Levels With Epoetin Alfa in Mainly Nonanemic Patients With Metastatic Breast Cancer Receiving First-Line Chemotherapy: A Survival Study

Brian Leyland-Jones, Vladimir Semiglazov, Marek Pawlicki, Tadeusz Pienkowski, Sergei Tjulandin, George Manikhas, Antoly Makhson, Anton Roth, David Dodwell, Jose Baselga, Mikhail Biakhov, Konstantinas Valuckas, Edouard Voznyi, Xiangyang Liu, Els Vercammen

From the Department of Medical Oncology, McGill University, Montreal, Canada; N.N. Petrov Research Institute of Oncology; City Oncology Dispensary, St Petersburg; Cancer Research Center; Semashko Central Clinical Hospital; Russian Scientific Center of Radiology, Moscow; City Clinical Hospital, Moscow Region, Russia; Klinika Chemioterapii Centrum Onkologii, Krakov; Klinika Nowotworów Sutka Centrum Onkologii Instytut, Warsaw, Poland; Klinika za Tumore, Zagreb, Croatia; Johnson & Johnson Pharmaceutical Research & Development, High Wycombe, Bucks, United Kingdom; Lithuanian Oncology Centre, Vilnius, Lithuania; and Johnson & Johnson Pharmaceutical Research & Development, Raritan, NJ

Address reprint requests to and address for reprints: Brian Leyland-Jones, MD, Department of Oncology, McGill University, 546 Pine Avenue W, Montreal, Quebec, Canada H2W 1S6; e-mail: brian.leyland-jones{at}mcgill.ca

PURPOSE: To evaluate the effect on survival and quality of life of maintaining hemoglobin (Hb) in the range of 12 to 14 g/dL with epoetin alfa versus placebo in women with metastatic breast cancer (MBC) receiving first-line chemotherapy.

PATIENTS AND METHODS: Eligible patients were randomly assigned to receive epoetin alfa 40,000 U once weekly or placebo for 12 months. Study drug was initiated if baseline Hb was ≤ 13 g/dL or when Hb decreased to ≤ 13g/dL during the study. The primary end point was 12-month overall survival (OS).

RESULTS: The study drug administration was stopped early in accordance with a recommendation from the Independent Data Monitoring Committee because of higher mortality in the group treated with epoetin alfa. Enrollment had been completed, with 939 patients enrolled (epoetin alfa, n = 469; placebo, n = 470). Most patients had Hb more than 12 g/dL at baseline (median Hb, 12.8 g/dL) or during the study. From the final analysis, 12-month OS was 70% for epoetin alfa recipients and 76% for placebo recipients (P = .01). Optimal tumor response and time to disease progression were similar between groups. The reason for the difference in mortality between groups could not be determined from additional subsequent analyses involving both study data and chart review.

CONCLUSION: In this trial, the use of epoetin alfa to maintain high Hb targets in women with MBC, most of whom did not have anemia at the start of treatment, was associated with decreased survival. Additional research is required to clarify the potential impact of erythropoietic agents on survival when the Hb target range is 10 to 12 g/dL.

Supported by a research grant from Johnson & Johnson Pharmaceutical Research and Development LLC, Raritan, NJ. B.L.-J. was the principal investigator.

Portions of this study were reported previously in Leyland-Jones B, and the BEST Investigators and Study Group: Breast cancer trial with erythropoietin terminated unexpectedly. Lancet Oncol 4:459-460, 2003.

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


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