The International Multicenter Pooled Analysis of
Colon Cancer Trials (IMPACT) investigators have now completed two large systematic reviews of adjuvant
therapy trials in
colon cancer. The IMPACT 1 study pooled data from three separate trials each comparing the efficacy of
5-fluorouracil (5-FU)/
leucovorin with observation alone as adjuvant treatment for 1,526 patients with Dukes' B or C
colon cancer. The results showed that treatment with 5-FU/
leucovorin significantly reduced mortality by 22% (P = .029) and events such as relapse, second
tumor, or death by 35% (P < .0001) after 3 years of follow-up. The side effects associated with 5-FU/
leucovorin were clinically acceptable. The IMPACT 1 study also showed a clear benefit of adjuvant treatment for patients with Dukes' C
colon cancer, but not for stage-B patients. After up to 10 years of follow-up, 5-FU/
leucovorin significantly reduced mortality by 30% for patients with Dukes' C disease (P = .003), but only reduced mortality by 8% in patients with Dukes' B
colon cancer (P = .658). The aim of the IMPACT 2 study was to determine whether 5-FU/
leucovorin is an effective adjuvant treatment for patients with Dukes' B2
colon cancer. Results were pooled from five separate trials that randomized 1,016 patients. After a median of 5.75 years of follow-up, B2 patients receiving 5-FU/
leucovorin did not have a significant increase in overall survival or event-free survival. At 5 years, the hazard ratio for overall survival was 0.86 (90% confidence interval, 0.68 to 1.07) and for event-free survival was 0.83 (90% confidence interval, 0.72 to 1.07).
5-Fluorouracil/
leucovorin was not recommended as a standard adjuvant treatment for all patients with Dukes' B2
colon cancer.