title: Adding epoetin alfa to intense dose-dense adjuvant chemotherapy for breast cancer: randomized clinical trial.
abstract: BACKGROUND
  The AGO-ETC trial compared 5-year relapse-free survival of intense dose-dense (IDD) sequential chemotherapy with epirubicin (E), paclitaxel (T), and cyclophosphamide (C) (IDD-ETC) every 2 weeks vs conventional scheduled epirubicin/cyclophosphamide followed by paclitaxel (EC→T) (every 3 weeks) as adjuvant treatment in high-risk breast cancer patients. The objective of this study was to evaluate the safety and efficacy of epoetin alfa in a second randomization of the intense dose-dense arm.
  
  
  METHODS
  One thousand two hundred eighty-four patients were enrolled; 658 patients were randomly assigned to the IDD-ETC treatment group. Within the IDD-ETC group, 324 patients were further randomly assigned to the epoetin alfa group, and 319 were randomly assigned to the non-erythropoiesis-stimulating agent (ESA) control group. Primary efficacy endpoints included change in hemoglobin level from baseline to Cycle 9 and the percentage of subjects requiring red blood cell transfusion. Relapse-free survival, overall survival, and intramammary relapse were secondary endpoints estimated with Kaplan-Meier and Cox regression methods. Except for the primary hypothesis, all statistical tests were two-sided.
  
  
  RESULTS
  Epoetin alfa avoided the decrease in hemoglobin level (no decrease in the epoetin alfa group vs -2.20g/dL change for the control group; P < .001) and statistically significantly reduced the percentage of subjects requiring red blood cell transfusion (12.8% vs 28.1%; P < .0001). The incidence of thrombotic events was 7% in the epoetin alfa arm vs 3% in the control arm. After a median follow-up of 62 months, epoetin alfa treatment did not affect overall survival, relapse-free survival, or intramammary relapse.
  
  
  CONCLUSIONS
  Epoetin alfa resulted in improved hemoglobin levels and decreased transfusions without an impact on relapse-free or overall survival. However, epoetin alfa had an adverse effect, resulting in increased thrombosis.
authors.affiliation: Department of Gynecology and Obstetrics, Klinikum Frankfurt Höchst, Frankfurt, Germany. volker.moebus@klinikumfrankfurt.de
authors.forename: Volker
authors.initials: V
authors.lastname: Moebus
authors.forename: Christian
authors.initials: C
authors.lastname: Jackisch
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneeweiss
authors.forename: Jens
authors.initials: J
authors.lastname: Huober
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Lueck
authors.forename: Andreas
authors.initials: A
authors.lastname: du Bois
authors.forename: Christoph
authors.initials: C
authors.lastname: Thomssen
authors.forename: Christian
authors.initials: C
authors.lastname: Kurbacher
authors.forename: Walther
authors.initials: W
authors.lastname: Kuhn
authors.forename: Ulrike
authors.initials: U
authors.lastname: Nitz
authors.forename: Ingo B
authors.initials: IB
authors.lastname: Runnebaum
authors.forename: Axel
authors.initials: A
authors.lastname: Hinke
authors.forename: Rolf
authors.initials: R
authors.lastname: Kreienberg
authors.forename: Michael
authors.initials: M
authors.lastname: Untch
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001803:Blood Transfusion / Q000706:statistics & numerical data; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006397:Hematinics / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D016016:Proportional Hazards Models; D011788:Quality of Life; D011994:Recombinant Proteins / Q000627:therapeutic use; D018570:Risk Assessment; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D006397:Hematinics; D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D015251:Epirubicin; D000068817:Epoetin Alfa; D003520:Cyclophosphamide; D017239:Paclitaxel