Maintaining normal hemoglobin levels with epoetin alfa in mainly nonanemic patients with metastatic breast cancer receiving first-line chemotherapy: a survival study

J Clin Oncol. 2005 Sep 1;23(25):5960-72. doi: 10.1200/JCO.2005.06.150. Epub 2005 Aug 8.

Abstract

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 < or = 13 g/dL or when Hb decreased to < or = 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anemia
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Epoetin Alfa
  • Erythropoietin / adverse effects*
  • Erythropoietin / therapeutic use*
  • Female
  • Hematinics / adverse effects*
  • Hematinics / therapeutic use*
  • Hemoglobins / analysis*
  • Humans
  • Injections, Subcutaneous
  • Middle Aged
  • Neoplasm Metastasis
  • Placebos
  • Quality of Life
  • Recombinant Proteins
  • Survival Analysis

Substances

  • Hematinics
  • Hemoglobins
  • Placebos
  • Recombinant Proteins
  • Erythropoietin
  • Epoetin Alfa