Adjuvant chemotherapy in the treatment of colon cancer: randomized multicenter trial of the Italian National Intergroup of Adjuvant Chemotherapy in Colon Cancer (INTACC)

Ann Oncol. 2003 Sep;14(9):1365-72. doi: 10.1093/annonc/mdg359.


Background: To determine whether the addition of leucovorin to the combination 5-fluorouracil plus levamisole prolongs disease-free survival and overall survival in patients with radically resected colon cancer (Dukes' B(2-3) and C).

Patients and methods: Patients (1703) were accrued between March 1992 and February 1995 in a large-scale clinical trial within five Italian cooperative groups. After stratification for center, patients were randomized as follows: arm A, 5-fluorouracil [450 mg/m(2) intravenous (i.v.) bolus on days 1-5] and levamisole (150 mg orally for 3 days, every 14 days for 6 months) versus arm B, 6-S-leucovorin (100 mg/m(2) i.v. bolus on days 1-5) followed by 5-fluorouracil (370 mg/m(2) i.v. bolus on days 1-5), plus levamisole (as arm A), every 4 weeks for six cycles.

Results: After a median follow-up of 6.4 years no significant difference was seen for either disease-free survival (58% versus 60%, not significant) or 5-year overall survival (68% versus 71%, not significant), respectively. Gastrointestinal toxicity (World Health Organization grade 3/4) was more frequent in arm B (8% versus 18%, not significant).

Conclusions: In this trial the schedules used showed no statistically significant differences in terms of disease-free survival or overall survival in the treatment of colorectal cancer.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemotherapy, Adjuvant
  • Colonic Neoplasms / drug therapy*
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Fluorouracil / therapeutic use*
  • Follow-Up Studies
  • Humans
  • Leucovorin / administration & dosage
  • Leucovorin / therapeutic use*
  • Levamisole / administration & dosage
  • Levamisole / adverse effects
  • Levamisole / therapeutic use*
  • Male
  • Middle Aged
  • Treatment Outcome


  • Levamisole
  • Leucovorin
  • Fluorouracil