title: Long-term benefit of high-dose epirubicin in adjuvant chemotherapy for node-positive breast cancer: 15-year efficacy results of the Belgian multicentre study.
abstract: OBJECTIVE
  The 4-year results of this trial demonstrated that a higher dose of epirubicin with cyclophosphamide (HEC) is superior to a lower dose of epirubicin, 60 mg/m(2) (EC), for event-free survival (EFS; 27% reduction), but is not superior to classical oral cyclophosphamide, methotrexate, and fluorouracil (CMF) in the adjuvant treatment of node-positive breast cancer. Herein we report the 15-year data on efficacy and long-term toxicity of this three-arm Belgian multicenter trial.
  
  
  METHODS
  Between March 1988 and December 1996, 777 eligible patients were randomly assigned to six cycles of CMF, eight cycles of EC, or eight cycles HEC.
  
  
  RESULTS
  The 15-year EFS was 45% for patients who received CMF, 39% for patients who received EC, and 50% for patients who received HEC. The hazard ratios (HR) were 0.77 for HEC versus EC (95% CI, 0.60 to 0.98; P = .03), 0.90 for HEC versus CMF (P = .39), and 0.86 for EC versus CMF (P = .21). No difference in overall survival (OS) was seen. Cardiac toxicity was more frequent with HEC than with CMF (11 patients v 1 patient; P = .006), but no more than with EC (P = .21).
  
  
  CONCLUSIONS
  Treatment with HEC demonstrated superior EFS when compared with lower-dose epirubicin. However, we do not recommend the use of HEC regimen in daily clinical practice, mainly because of the higher risk of cardiotoxicity related to the cumulative doses of epirubicin and the lack of superiority of anthracyclines over CMF in our study.
authors.affiliation: Institut Jules Bordet and Université Libre de Bruxelles, Brussels.
authors.forename: Evandro
authors.initials: E
authors.lastname: de Azambuja
authors.forename: Marianne
authors.initials: M
authors.lastname: Paesmans
authors.forename: Marc
authors.initials: M
authors.lastname: Beauduin
authors.forename: Anita
authors.initials: A
authors.lastname: Vindevoghel
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cornez
authors.forename: Claude
authors.initials: C
authors.lastname: Finet
authors.forename: Fernand
authors.initials: F
authors.lastname: Ries
authors.forename: Marie Thérèse
authors.initials: MT
authors.lastname: Closon-Dejardin
authors.forename: Joseph
authors.initials: J
authors.lastname: Kerger
authors.forename: Philippe
authors.initials: P
authors.lastname: Gobert
authors.forename: Christian
authors.initials: C
authors.lastname: Focan
authors.forename: Alain
authors.initials: A
authors.lastname: Tagnon
authors.forename: Stella
authors.initials: S
authors.lastname: Dolci
authors.forename: Jean M
authors.initials: JM
authors.lastname: Nogaret
authors.forename: Angelo
authors.initials: A
authors.lastname: di Leo
authors.forename: Martine J
authors.initials: MJ
authors.lastname: Piccart-Gebhart
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001530:Belgium; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage*; D005260:Female; D005472:Fluorouracil; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008727:Methotrexate; D008875:Middle Aged
chemical_list: D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate