title: Randomized trial comparing six versus three cycles of epirubicin-based adjuvant chemotherapy in premenopausal, node-positive breast cancer patients: 10-year follow-up results of the French Adjuvant Study Group 01 trial.
abstract: OBJECTIVE
  To evaluate the duration and dose intensity of epirubicin-based regimens in premenopausal patients with lymph node-positive breast cancer.
  
  
  METHODS
  Between 1986 and 1990, 621 patients with operable breast cancer were randomly assigned to receive fluorouracil (Roche SA, Basel, Switzerland) 500 mg/m2, epirubicin (Pharmacia SA, Milan, Italy) 50 mg/m2, and cyclophosphamide (Asta Medica AG, Frankfurt, Germany) 500 mg/m2 every 21 days (FEC 50) for six cycles (6 FEC 50); FEC 50 for three cycles (3 FEC 50); or the same regimen with epirubicin 75 mg/m2 (FEC 75) for three cycles (3 FEC 75). All patients in the three arms received chest wall irradiation at the end of the third cycle.
  
  
  RESULTS
  After a 131-month median follow-up, the 10-year disease-free survival (DFS) was 53.4%, 42.5%, and 43.6% (P =.05) in the three arms, respectively. Pairwise comparisons demonstrate that 6 FEC 50 was superior both to 3 FEC 50 (P =.02) and to 3 FEC 75 (P =.05). The 10-year overall survival (OS) for the 6 FEC 50 arm was 64.3%, for the 3 FEC 50 arm it was 56.6%, and for the 3 FEC 75 arm, it was 59.7% (P =.25), respectively. Pairwise comparisons demonstrate that 6 FEC 50 was more effective than 3 FEC 50 (P =.10). Cox regression analysis demonstrates that OS was significantly better in the 6 FEC 50 than in the 3 FEC 50 arm (P =.046). No severe infections (grade 3 to 4), acute cardiac toxicity, or deaths from toxicity have been observed. Only five patients developed delayed cardiac dysfunctions, and three patients developed acute myeloblastic leukemia.
  
  
  CONCLUSIONS
  After a long-term follow-up in an adjuvant setting, the benefit of six cycles of FEC 50 compared with three cycles, whatever the dose, is highly significant in terms of DFS. As regards OS, the group receiving six cycles of FEC 50 has significantly better results than the group receiving three cycles of FEC 50.
authors.affiliation: Département d'Oncologie Médicale, Centre René Gauducheau, Nantes, France. fumoleau@gauducheau-nantes.fnclcc.fr
authors.forename: Pierre
authors.initials: P
authors.lastname: Fumoleau
authors.forename: Pierre
authors.initials: P
authors.lastname: Kerbrat
authors.forename: Pascale
authors.initials: P
authors.lastname: Romestaing
authors.forename: Pierre
authors.initials: P
authors.lastname: Fargeot
authors.forename: Alain
authors.initials: A
authors.lastname: Brémond
authors.forename: Moïse
authors.initials: M
authors.lastname: Namer
authors.forename: Simon
authors.initials: S
authors.lastname: Schraub
authors.forename: Marie-Jo
authors.initials: MJ
authors.lastname: Goudier
authors.forename: Jeanne
authors.initials: J
authors.lastname: Mihura
authors.forename: Alain
authors.initials: A
authors.lastname: Monnier
authors.forename: Pierre
authors.initials: P
authors.lastname: Clavère
authors.forename: Daniel
authors.initials: D
authors.lastname: Serin
authors.forename: Philippe
authors.initials: P
authors.lastname: Seffert
authors.forename: Christiane
authors.initials: C
authors.lastname: Pourny
authors.forename: Thomas
authors.initials: T
authors.lastname: Facchini
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Jacquin
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Sztermer
authors.forename: Jean
authors.initials: J
authors.lastname: Datchary
authors.forename: René
authors.initials: R
authors.lastname: Ramos
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Luporsi
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008875:Middle Aged; D017697:Premenopause; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil