title: Intensification of adjuvant chemotherapy: 5-year results of a randomized trial comparing conventional doxorubicin and cyclophosphamide with high-dose mitoxantrone and cyclophosphamide with filgrastim in operable breast cancer with 10 or more involved axillary nodes.
abstract: OBJECTIVE
  To determine whether intensifying the dose of adjuvant chemotherapy improves the outcome of women with primary breast cancer and 10 or more involved axillary nodes.
  
  
  METHODS
  Patients (n = 150) were randomized to receive either four cycles of standard doxorubicin 60 mg/m(2) plus cyclophosphamide 600 mg/m(2) every 3 weeks (arm A) or four courses of intensified mitoxantrone 23 mg/m(2) plus cyclophosphamide 600 mg/m(2), with filgrastim 5 g/kg/d from days 2 to 15, every 3 weeks (arm B). Disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) were determined using life-table estimates.
  
  
  RESULTS
  There were no significant differences in DFS (P =.44), DDFS (P =.67), or OS (P =.99) between the two groups at 5 years; DDFS was 45% (arm A) versus 50% (arm B), and DFS was 41% versus 49%, respectively. Five-year survival was similar in both arms (61% v 60%, respectively). Failure to note an intergroup difference in outcome was unrelated to relative dose-intensity. Analysis of patients with 15 or more positive nodes revealed a significant difference in 5-year DDFS (19% v 49% in arm B; P =.01). Toxicity was generally mild in both groups, with no toxic death. The incidence of febrile neutropenia was low (0.3% v 3%). Alopecia was less frequent in arm B (P <.001).
  
  
  CONCLUSIONS
  This randomized trial confirms the feasibility of administering mitoxantrone 23 mg/m(2) with cyclophosphamide and filgrastim. Although there was no significant difference between conventional and intensified arms at 5 years, according to subgroup analysis, intensified treatment may decrease the risk of relapse in patients with 15 or more positive nodes compared with doxorubicin an cyclophosphamide.
authors.affiliation: Department of Medical Oncology, Centre René Gauducheau, Centre Regional de Lutte Contre le Cancer Nantes-Atlantique, Nantes. fumoleau@nantes.fnclcc.fr
authors.forename: P
authors.initials: P
authors.lastname: Fumoleau
authors.forename: F
authors.initials: F
authors.lastname: Chauvin
authors.forename: M
authors.initials: M
authors.lastname: Namer
authors.forename: R
authors.initials: R
authors.lastname: Bugat
authors.forename: M
authors.initials: M
authors.lastname: Tubiana-Hulin
authors.forename: J P
authors.initials: JP
authors.lastname: Guastalla
authors.forename: T
authors.initials: T
authors.lastname: Delozier
authors.forename: P
authors.initials: P
authors.lastname: Kerbrat
authors.forename: Y
authors.initials: Y
authors.lastname: Devaux
authors.forename: J
authors.initials: J
authors.lastname: Bonneterre
authors.forename: A
authors.initials: A
authors.lastname: Filleul
authors.forename: M
authors.initials: M
authors.lastname: Clavel
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001365:Axilla; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D011994:Recombinant Proteins; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D004317:Doxorubicin; D003520:Cyclophosphamide; D008942:Mitoxantrone; D000069585:Filgrastim