title: Randomized, double-blind, placebo-controlled trial of erythropoietin in non-small-cell lung cancer with disease-related anemia.
abstract: OBJECTIVE
  Previous trials have suggested a quality-of-life (QOL) improvement for anemic cancer patients treated with erythropoietin, but few used QOL as the primary outcome. We designed a trial to investigate the effects of epoetin alfa therapy on the QOL of anemic patients with advanced non-small-cell carcinoma of the lung (NSCLC).
  
  
  METHODS
  A multicenter, randomized, double-blind, placebo-controlled trial was conducted. The proposed sample size was 300 patients. Eligible patients were required to have NSCLC unsuitable for curative therapy and baseline hemoglobin (Hgb) levels less than 121 g/L. Patients were assigned to 12 weekly injections of subcutaneous epoetin alpha or placebo, targeting Hgb levels between 120 and 140 g/L. The primary outcome was the difference in the change in Functional Assessment of Cancer Therapy-Anemia scores between baseline and 12 weeks.
  
  
  RESULTS
  Reports of thrombotic events in other epoetin trials prompted an unplanned safety analysis after 70 patients had been randomly assigned (33 to the active arm and 37 to the placebo arm). This revealed a significant difference in the median survival in favor of the patients on the placebo arm of the trial (63 v 129 days; hazard ratio, 1.84; P = .04). The Steering Committee closed the trial. Patient numbers compromised the interpretation of the QOL analysis, but a positive Hgb response was noted with epoetin alfa treatment.
  
  
  CONCLUSIONS
  An unplanned safety analysis suggested decreased overall survival in patients with advanced NSCLC treated with epoetin alfa. Although infrequent, other similar reports highlight the need for ongoing trials evaluating erythropoietin receptor agonists to ensure that overall survival is monitored closely.
authors.affiliation: Juravinski Cancer Center at Hamilton Health Sciences, Hamilton, Ontario, Canada. jim.wright@hrcc.on.ca
authors.forename: James R
authors.initials: JR
authors.lastname: Wright
authors.forename: Yee C
authors.initials: YC
authors.lastname: Ung
authors.forename: Jim A
authors.initials: JA
authors.lastname: Julian
authors.forename: Kathleen I
authors.initials: KI
authors.lastname: Pritchard
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Whelan
authors.forename: Column
authors.initials: C
authors.lastname: Smith
authors.forename: Barbara
authors.initials: B
authors.lastname: Szechtman
authors.forename: Wilson
authors.initials: W
authors.lastname: Roa
authors.forename: Liam
authors.initials: L
authors.lastname: Mulroy
authors.forename: Leona
authors.initials: L
authors.lastname: Rudinskas
authors.forename: Bruno
authors.initials: B
authors.lastname: Gagnon
authors.forename: Gord S
authors.initials: GS
authors.lastname: Okawara
authors.forename: Mark N
authors.initials: MN
authors.lastname: Levine
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D002170:Canada; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications* / Q000401:mortality / Q000473:pathology; D004311:Double-Blind Method; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006397:Hematinics / Q000009:adverse effects / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000150:complications* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D011788:Quality of Life; D011994:Recombinant Proteins; D013927:Thrombosis / Q000139:chemically induced; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D006397:Hematinics; D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa