title: Phase III trial of concurrent or sequential adjuvant chemoradiotherapy after conservative surgery for early-stage breast cancer: final results of the ARCOSEIN trial.
abstract: OBJECTIVE
  In 1996, we initiated the French multicenter phase III randomized trial to compare the effect on disease-free survival (DFS) of concurrent versus sequential chemotherapy (CT) and radiotherapy (RT) after breast-conserving surgery for stages I and II breast cancer. This report presents the clinical results with a median follow-up of 60 months.
  
  
  METHODS
  Between February 1996 and April 2000, 716 patients were entered onto this trial. Adjuvant treatment began within 6 weeks after surgery. Sequential treatment of CT administered first followed by RT was compared with concurrent treatment of CT administered with RT. The CT regimen consisted of mitoxantrone (12 mg/m2), fluorouracil (500 mg/m2), and cyclophosphamide (500 mg/m2) on day 1, and it was repeated every 21 days for six courses. RT was delivered to the breast and, when indicated, to the regional lymphatics.
  
  
  RESULTS
  There was no statistically significant difference in treatment in the 5-year DFS (80% in both groups; P = .83), locoregional recurrence-free survival (LRFS; 92% in sequential v 95% in concurrent; P = .76), metastasis-free survival (87% in sequential v 84% in concurrent; P = .55), or overall survival (90% in sequential v 91% in concurrent; P = .76). Nevertheless, in the node-positive subgroup, the 5-year LRFS was statistically better in the concurrent arm (97% in concurrent v 91% in sequential; P = .02), corresponding to a risk of locoregional recurrence decreased by 39% (hazard ratio, 0.61; 95% CI, 0.38 to 0.93).
  
  
  CONCLUSIONS
  This treatment protocol remains an appealing clinical option for many women with operable breast cancer at a high risk of recurrence. Combination treatments with new drugs for breast cancer are warranted.
authors.affiliation: Department of Radiation Oncology, Henry Kaplan, Hôpital Bretonneau, Tours, France. alain.toledano@gmail.com
authors.forename: Alain
authors.initials: A
authors.lastname: Toledano
authors.forename: David
authors.initials: D
authors.lastname: Azria
authors.forename: Pascal
authors.initials: P
authors.lastname: Garaud
authors.forename: Alain
authors.initials: A
authors.lastname: Fourquet
authors.forename: Daniel
authors.initials: D
authors.lastname: Serin
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Bosset
authors.forename: Joelle
authors.initials: J
authors.lastname: Miny-Buffet
authors.forename: Anne
authors.initials: A
authors.lastname: Favre
authors.forename: Olivier
authors.initials: O
authors.lastname: Le Floch
authors.forename: Gilles
authors.initials: G
authors.lastname: Calais
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local; D018714:Radiotherapy, Adjuvant; D016896:Treatment Outcome
chemical_list: D003520:Cyclophosphamide; D008942:Mitoxantrone; D005472:Fluorouracil