Efficacy of adjuvant fluorouracil and folinic acid in colon cancer. International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) investigators.

The role of fluorouracil and folinic acid and adjuvant therapy for colon cancer is not clear. We undertook independently three randomised trials to find out the efficacy of fluorouracil and high-dose folinic acid after surgery for Dukes' B and C stage colon cancer. The three studies by the Gruppo Interdisciplinare Valutazione Interventi Oncologia (GIVIO), the National Cancer Institute Canada Clinical Trials Group (NCIC-CTG), and the Fondation Française de Cancerologie Digestive (FFCD) were pooled for combined analysis. Each trial was multicentre and used the same treatment regimen (fluorouracil 370-400 mg/m2 plus folinic acid 200 mg/m2 daily for 5 days, every 28 days for 6 cycles). A pooled analysis of the results was done on the basis of a previously agreed protocol when there were sufficient events to detect at least a 10% reduction in mortality with 80% power. 1526 patients with resected B (56%) and C (44%) carcinoma of the colon were enrolled and 1493 were confirmed as eligible. 736 were assigned to the treatment group and 757 to the control group. Fluorouracil/folinic acid significantly reduced mortality by 22% (95% CI 3-38; p = 0.029) and events by 35% (22-46; p < 0.0001), increasing 3-year event-free survival from 62% to 71% and overall survival from 78% to 83%. Compliance with treatment was good; more than 80% of patients completed the planned treatment. Side-effects were clinically acceptable with only 1 treatment-related death. The commonest side-effects were gastrointestinal, but severe toxic effects (WHO grade 4) occurred in fewer than 3% of cases. We conclude that fluorouracil plus high-dose folinic acid is a well-tolerated and effective 6-month adjuvant regimen for colon cancer.