title: A phase III randomised trial of LV5FU2 + irinotecan versus LV5FU2 alone in adjuvant high-risk colon cancer (FNCLCC Accord02/FFCD9802).
abstract: BACKGROUND
  This multicenter adjuvant phase III trial evaluated the addition of irinotecan to LV5FU2 in colon cancer patients at high risk of relapse.
  
  
  METHODS
  A total of 400 patients with histologically proven primary colon cancer with postoperative N1 detected by occlusion/perforation or N2 were randomised to: A-LV5FU2 [leucovorin 200 mg/m(2), 2-h infusion, 5-fluorouracil (5-FU) 400 mg/m(2) bolus, 600 mg/m(2) 22-h continuous infusion, days 1 and 2] or B-LV5FU2 + IRI (irinotecan 180 mg/m(2) 90-min infusion day 1 + LV5FU2) fortnightly for 12 cycles. Primary end point was disease-free survival (DFS).
  
  
  RESULTS
  Median follow-up was 63 months. Significantly more T4 tumours and 15 or more positive lymph nodes were observed in arm B. 5-FU relative dose intensity (RDI) was >0.80 for 94% and 77% in arms A and B, respectively (P < 0.001). Irinotecan RDI was >0.80 for 70% patients. There were more grades 3 and 4 neutropenia in arm B (4% versus 28%, P < 0.001). The 3-year DFS was 60% [95% confidence interval (CI) 53% to 66%] and 51% (95% CI 44% to 58) in arms A and B, respectively. No difference was observed [hazard ratio (HR) = 1.12, 95% CI 0.85-1.47, P = 0.42] even when adjusted for prognostic factors (adjusted HR = 0.98, 95% CI 0.74-1.31, P = 0.92). The 5-year overall survival (OS) was 67% (95% CI 59% to 73%) and 61% (95% CI 53% to 67%) in arms A and B, respectively.
  
  
  CONCLUSIONS
  Adjuvant LV5FU2 + IRI compared with LV5FU2 alone in patients at high risk of relapse showed no improvement in DFS and OS.
authors.affiliation: Centre de Recherche et de Lutte contre le Cancer Val d'Aurelle, Montpellier, France. marc.ychou@valdorel.fnclcc.fr
authors.forename: M
authors.initials: M
authors.lastname: Ychou
authors.forename: J-L
authors.initials: JL
authors.lastname: Raoul
authors.forename: J-Y
authors.initials: JY
authors.lastname: Douillard
authors.forename: S
authors.initials: S
authors.lastname: Gourgou-Bourgade
authors.forename: R
authors.initials: R
authors.lastname: Bugat
authors.forename: L
authors.initials: L
authors.lastname: Mineur
authors.forename: F
authors.initials: F
authors.lastname: Viret
authors.forename: Y
authors.initials: Y
authors.lastname: Becouarn
authors.forename: O
authors.initials: O
authors.lastname: Bouché
authors.forename: E
authors.initials: E
authors.lastname: Gamelin
authors.forename: M
authors.initials: M
authors.lastname: Ducreux
authors.forename: T
authors.initials: T
authors.lastname: Conroy
authors.forename: J-F
authors.initials: JF
authors.lastname: Seitz
authors.forename: L
authors.initials: L
authors.lastname: Bedenne
authors.forename: A
authors.initials: A
authors.lastname: Kramar
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D003110:Colonic Neoplasms / Q000188:drug therapy*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D018570:Risk Assessment
chemical_list: D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin