Monoclonal antibody therapy for resected Dukes' C colorectal cancer:: Seven-year outcome of a multicenter randomized trial

Purpose: As previously shown, antibody treatment increased survival of patients with resected colorectal cancer of stage Dukes' C. Since the 5-year analysis was criticized because of the wide range (2.7 to 7.5 years) of follow-up time, we performed a 7-year analysis with only four of 189 patients monitored for less than 5 years. Patients and Methods: A total of 189 patients with resected Dukes' C colorectal cancer were randomly allocated to infusions of a total of 900 mg 17-1A antibody, 500 mg postoperatively followed by 4 monthly doses of 100 mg (n = 99), or to observation only (n = 90). Primary end points were overall survival and disease-free interval. Patients were stratified by a dynamic randomization according to center, sex, location of tumor, number of affected lymph nodes, and preoperative carcinoembryonic antigen concentration. Results: Randomization produced balanced distribution of risk factors. After 7 years of follow-vp evaluation, treatment had reduced overall mortality by 32% (Cox's proportional hazard, P < .01; log-rank, P = .01) and decreased the recurrence rate by 23% (Cox's proportional hazard, P < .04; log-rank, P = .07). The intention-to-treat analysis gave a significant effect for overall survival (Cox's proportional hazard, P < .01; log-rank, P = .02) and disease-free survival (Cox's proportional hazard, P = .02; log-rank, P = .11). While distant metastases were significantly reduced (Cox's proportional hazard, P = .004; log-rank, P = .004), local relapses were not (Cox's proportional hazard, P = .65; log-rank, P = .52). This differential effect of 17-1A antibody on disseminated isolated tumor cells versus occult local satellites may explain the increased significance seen in the overall survival. Conclusion: The now-matured study shows that 17-1A antibody administered after surgery prevents the development of distant metastasis in approximately one third of patients. The therapeutic effect is maintained after 7 years of follow up evaluation. (C) 1998 by American Society of Clinical Oncology.