North Central Cancer Treatment Group--Mayo Clinic trials in colon cancer.

The adjuvant treatment of colon cancer is now accepted as an effective therapy following surgical resection of the primary tumor in patients at high risk for relapse. Results of studies conducted in the last 10 years have confirmed the benefits of using various 5-fluorouracil (5-FU)-based chemotherapy regimens to decrease recurrence rates and improve patient survival. The North Central Cancer Treatment Group-Mayo Clinic studies have made a significant contribution to establishing the role of adjuvant therapy in colon cancer. Our first study to suggest the effectiveness of adjuvant chemotherapy in patients with stage III disease was reported in 1989. The study used a combination of 5-FU and the anthelminthic agent levamisole, tested because of its ability to positively modulate the human cellular immune system. The results of this study were confirmed by a larger Intergroup study (0035) showing significant decreases in relapse and death rates in stage III colon cancer patients treated with 5-FU plus levamisole compared with surgery alone. Clinical trials conducted throughout the 1990s tested various 5-FU based regimens against the standard 5-FU and levamisole combination. From these trials, the combination of 5-FU plus leucovorin emerged as the standard surgical adjuvant treatment of colon cancer. The efficacy of treatment with this regimen for 6 months was similar to that of a 1-year 5-FU plus levamisole regimen. These findings led to the design of trials in which 5-FU was combined with both leucovorin and levamisole. No differences in efficacy were found in any of the various combinations tested. Current clinical trials are investigating the use of newer agents such as CPT-II in the adjuvant setting. The results of these trials may further improve the efficacy of adjuvant therapy in patients with high-risk colon cancer.