title: Prospectively randomized trial of postoperative adjuvant chemotherapy in patients with high-risk colon cancer.
abstract: OBJECTIVE
  This study had two major goals: (1) to assess the effectiveness of a regimen of fluorouracil (5-FU) plus levamisole plus leucovorin as postoperative surgical adjuvant therapy for patients with high-risk colon cancer, and (2) to evaluate 6 months versus 12 months of chemotherapy.
  
  
  METHODS
  Patients with poor-prognosis stage II or III colon cancer were randomly assigned to receive adjuvant chemotherapy with either intensive-course 5-FU and leucovorin combined with levamisole, or a standard regimen of 5-FU plus levamisole. Patients were also randomly assigned to receive either 12 months or 6 months of chemotherapy, which resulted in four treatment groups.
  
  
  RESULTS
  Eight hundred ninety-one of 915 patients entered (97.4%) were eligible. The median follow-up duration is 5.1 years for patients still alive. There was a difference among the four treatment groups with respect to patient survival, and a significant duration-by-regimen interaction was observed. Specifically, standard 5-FU plus levamisole was inferior to 5-FU plus leucovorin plus levamisole when treatment was given for 6 months (5-year survival rate, 60% v 70%; P < .01).
  
  
  CONCLUSIONS
  There was no significant improvement in patient survival when chemotherapy was given for 12 months compared with 6 months. When chemotherapy was given for 6 months, standard 5-FU plus levamisole was associated with inferior patient survival compared with intensive-course 5-FU plus leucovorin plus levamisole. These data suggest that 5-FU plus levamisole for 6 months should not be used in clinical practice, whereas 6 months of treatment with 5-FU plus leucovorin plus levamisole is effective.
authors.affiliation: Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. oconnell.michael@mayo.edu
authors.forename: M J
authors.initials: MJ
authors.lastname: O'Connell
authors.forename: J A
authors.initials: JA
authors.lastname: Laurie
authors.forename: M
authors.initials: M
authors.lastname: Kahn
authors.forename: R J
authors.initials: RJ
authors.lastname: Fitzgibbons
authors.forename: C
authors.initials: C
authors.lastname: Erlichman
authors.forename: L
authors.initials: L
authors.lastname: Shepherd
authors.forename: C G
authors.initials: CG
authors.lastname: Moertel
authors.forename: W I
authors.initials: WI
authors.lastname: Kocha
authors.forename: R
authors.initials: R
authors.lastname: Pazdur
authors.forename: H S
authors.initials: HS
authors.lastname: Wieand
authors.forename: J
authors.initials: J
authors.lastname: Rubin
authors.forename: A M
authors.initials: AM
authors.lastname: Vukov
authors.forename: J H
authors.initials: JH
authors.lastname: Donohue
authors.forename: J E
authors.initials: JE
authors.lastname: Krook
authors.forename: A
authors.initials: A
authors.lastname: Figueredo
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000931:Antidotes / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D007978:Levamisole / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies
chemical_list: D000276:Adjuvants, Immunologic; D000931:Antidotes; D007978:Levamisole; D002955:Leucovorin; D005472:Fluorouracil