title: A phase III randomized trial comparing adjuvant concomitant chemoradiotherapy versus standard adjuvant chemotherapy followed by radiotherapy in operable node-positive breast cancer: final results.
abstract: OBJECTIVE
  To compare concomitant and sequential adjuvant chemoradiotherapy regimens in node-positive, operable breast cancer patients.
  
  
  METHODS
  This was a randomized, French, multicenter, phase III trial enrolling 638 eligible women with prior breast surgery and positive axillary dissection. Patients in Arm A received 500 mg/m2 5-fluorouracil, 12 mg/m2 mitoxantrone, and 500 mg/m2 cyclophosphamide, with concomitant radiotherapy (50 Gy +/- 10-20-Gy boost). Patients in Arm B received 500 mg/m2 5-fluorouracil, 60 mg/m2 epirubicin, and 500 mg/m2 cyclophosphamide, with subsequent radiotherapy. Chemotherapy was administered on Day 1 every 21 days for 4 cycles.
  
  
  RESULTS
  Median treatment durations were 64 and 126 days (Arms A and B, respectively), with no significant difference in overall or disease-free survival. Five-year locoregional relapse-free survival favored patients with conservative surgery (two thirds of the population), with less local and/or regional recurrence in Arm A than in Arm B (3% vs. 9%; p = 0.01). Multivariate analysis in this subgroup showed a 2.8-fold increased risk of locoregional recurrence with sequential chemoradiotherapy, independent of other prognostic factors (p = 0.027). Febrile neutropenia and Grade 3-4 leukopenia were significantly more frequent in Arm A. Subclinical left ventricular ejection fraction events at 1 year were more frequent with concomitant radiotherapy (p = 0.02).
  
  
  CONCLUSIONS
  Concomitant radiotherapy with adjuvant fluorouracil, mitoxantrone, and cyclophosphamide has significantly better locoregional control in node-positive breast cancer after conservative surgery and 50% shorter treatment, albeit with slightly more acute toxicity. With mitoxantrone no longer available for adjuvant breast cancer treatment, alternative concomitant chemoradiotherapy studies are needed.
authors.affiliation: Centre René Huguenin, Saint-Cloud, France. j.rouesse@stcloud-huguenin.org
authors.forename: Jacques
authors.initials: J
authors.lastname: Rouëssé
authors.forename: Brigitte
authors.initials: B
authors.lastname: de la Lande
authors.forename: Frédérique
authors.initials: F
authors.lastname: Bertheault-Cvitkovic
authors.forename: Daniel
authors.initials: D
authors.lastname: Serin
authors.forename: Yvon
authors.initials: Y
authors.lastname: Graïc
authors.forename: Martin
authors.initials: M
authors.lastname: Combe
authors.forename: Bernard
authors.initials: B
authors.lastname: Leduc
authors.forename: Virginie
authors.initials: V
authors.lastname: Lucas
authors.forename: Liliane
authors.initials: L
authors.lastname: Demange
authors.forename: Tan Dat
authors.initials: TD
authors.lastname: Nguyen
authors.forename: Daniel
authors.initials: D
authors.lastname: Castèra
authors.forename: Claude
authors.initials: C
authors.lastname: Krzisch
authors.forename: Richard
authors.initials: R
authors.lastname: Villet
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Mouret-Fourme
authors.forename: Jean-Rémy
authors.initials: JR
authors.lastname: Garbay
authors.forename: Catherine
authors.initials: C
authors.lastname: Noguès
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D016001:Confidence Intervals; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D016609:Neoplasms, Second Primary / Q000145:classification; D018714:Radiotherapy, Adjuvant
chemical_list: D015251:Epirubicin; D003520:Cyclophosphamide; D008942:Mitoxantrone; D005472:Fluorouracil