title: Maintaining normal hemoglobin levels with epoetin alfa in mainly nonanemic patients with metastatic breast cancer receiving first-line chemotherapy: a survival study.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Oncology, McGill University, 546 Pine Avenue W, Montreal, Quebec, Canada H2W 1S6. brian.leyland-jones@mcgill.ca
authors.forename: Brian
authors.initials: B
authors.lastname: Leyland-Jones
authors.forename: Vladimir
authors.initials: V
authors.lastname: Semiglazov
authors.forename: Marek
authors.initials: M
authors.lastname: Pawlicki
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Pienkowski
authors.forename: Sergei
authors.initials: S
authors.lastname: Tjulandin
authors.forename: George
authors.initials: G
authors.lastname: Manikhas
authors.forename: Antoly
authors.initials: A
authors.lastname: Makhson
authors.forename: Anton
authors.initials: A
authors.lastname: Roth
authors.forename: David
authors.initials: D
authors.lastname: Dodwell
authors.forename: Jose
authors.initials: J
authors.lastname: Baselga
authors.forename: Mikhail
authors.initials: M
authors.lastname: Biakhov
authors.forename: Konstantinas
authors.initials: K
authors.lastname: Valuckas
authors.forename: Edouard
authors.initials: E
authors.lastname: Voznyi
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Liu
authors.forename: Els
authors.initials: E
authors.lastname: Vercammen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000009:adverse effects* / Q000627:therapeutic use*; D005260:Female; D006397:Hematinics / Q000009:adverse effects* / Q000627:therapeutic use*; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D007279:Injections, Subcutaneous; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010919:Placebos; D011788:Quality of Life; D011994:Recombinant Proteins; D016019:Survival Analysis
chemical_list: D006397:Hematinics; D006454:Hemoglobins; D010919:Placebos; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa