title: Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: who benefits and by how much?
abstract: OBJECTIVE
  Although it is well-established that fluorouracil- (FU-) based adjuvant therapy improves survival for patients with resected high-risk colon cancer, the magnitude of adjuvant therapy benefit across specific subgroups and for individual patients has been uncertain.
  
  
  METHODS
  Using a pooled data set of 3,302 patients with stage II and III colon cancer from seven randomized trials comparing FU + leucovorin or FU + levamisole to surgery alone, we performed an analysis based on a Cox proportional hazards regression model. Treatment, age, sex, tumor location, T stage, nodal status, and grade were tested for both prognostic and predictive significance. Model derived estimates of 5-year disease-free survival and overall survival (OS) for surgery alone and surgery plus FU-based therapy were calculated for a range of patient subsets.
  
  
  RESULTS
  Nodal status, T stage, and grade were the only prognostic factors independently significant for both disease-free survival and OS. Age was significant only for OS. In a multivariate analysis, adjuvant therapy showed a beneficial treatment effect across all subsets. Treatment benefits were consistent across sex, location, age, T-stage, and grade. A significant stage by treatment interaction was present, with treatment benefiting stage III patients to a greater degree than stage II patients.
  
  
  CONCLUSIONS
  Patients with high-risk resected colon cancer obtain benefit from FU-based therapy across subsets of age, sex, location, T stage, nodal status, and grade. Model estimates of survival stratified by T stage, nodal status, grade, and age are available at http://www.mayoclinic.com/calcs. This information may improve patients' and physicians' understanding of the potential benefits of adjuvant therapy.
authors.affiliation: Mayo Clinic and Foundation, Rochester, MN 55905, USA.
authors.forename: Sharlene
authors.initials: S
authors.lastname: Gill
authors.forename: Charles L
authors.initials: CL
authors.lastname: Loprinzi
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Sargent
authors.forename: Stephan D
authors.initials: SD
authors.lastname: Thomé
authors.forename: Steven R
authors.initials: SR
authors.lastname: Alberts
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Haller
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Benedetti
authors.forename: Guido
authors.initials: G
authors.lastname: Francini
authors.forename: Lois E
authors.initials: LE
authors.lastname: Shepherd
authors.forename: Jean
authors.initials: J
authors.lastname: Francois Seitz
authors.forename: Roberto
authors.initials: R
authors.lastname: Labianca
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Cha
authors.forename: Michael P
authors.initials: MP
authors.lastname: Heldebrant
authors.forename: Richard M
authors.initials: RM
authors.lastname: Goldberg
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D007978:Levamisole / Q000008:administration & dosage; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D016019:Survival Analysis; D014481:United States / Q000453:epidemiology
chemical_list: D007978:Levamisole; D002955:Leucovorin; D005472:Fluorouracil