title: The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Project protocol C-03.
abstract: OBJECTIVE
  This study was designed to evaluate the efficacy of leucovorin-modulated fluorouracil (5-FU) as adjuvant therapy for patients with Dukes' stage B and C colon cancer.
  
  
  METHODS
  Data are presented from 1,081 patients with Dukes' stage B and C carcinoma of the colon entered into National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol C-03 between August 1987 and April 1989. Patients were randomly assigned to receive either lomustine (MeCCNU), vincristine, and 5-FU (MOF), or leucovorin-modulated 5-FU (LV + 5-FU). The mean time on study was 47.6 months.
  
  
  RESULTS
  Comparison between the two groups indicates a disease-free survival advantage for patients treated with LV + 5-FU (P = .0004). The 3-year disease-free survival rate for patients in this group was 73% (95% confidence interval, 69% to 77%), compared with 64% (95% confidence interval, 60% to 68%) for patients receiving MOF. The corresponding percentage of patients surviving was 84% for those randomized to receive LV + 5-FU and 77% for the MOF-treated cohort (P = .003). At 3 years of follow-up, patients treated with postoperative LV + 5-FU had a 30% reduction in the risk of developing a treatment failure and a 32% reduction in mortality risk compared with similar patients treated with MOF.
  
  
  CONCLUSIONS
  Treatment with LV + 5-FU significantly prolongs disease-free survival and results in a significant benefit relative to overall survival. These findings, when considered together with results from a recent meta-analysis demonstrating a benefit from LV + 5-FU in advanced disease, provide evidence to support the concept of metabolic modulation of 5-FU.
authors.affiliation: National Surgical Adjuvant Breast and Bowel Project Headquarters, Pittsburgh, PA 15261.
authors.forename: N
authors.initials: N
authors.lastname: Wolmark
authors.forename: H
authors.initials: H
authors.lastname: Rockette
authors.forename: B
authors.initials: B
authors.lastname: Fisher
authors.forename: D L
authors.initials: DL
authors.lastname: Wickerham
authors.forename: C
authors.initials: C
authors.lastname: Redmond
authors.forename: E R
authors.initials: ER
authors.lastname: Fisher
authors.forename: J
authors.initials: J
authors.lastname: Jones
authors.forename: E P
authors.initials: EP
authors.lastname: Mamounas
authors.forename: L
authors.initials: L
authors.lastname: Ore
authors.forename: N J
authors.initials: NJ
authors.lastname: Petrelli
mesh_terms: D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use*; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016019:Survival Analysis
chemical_list: D002955:Leucovorin; D005472:Fluorouracil