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

• Published in: Journal of clinical oncology Vol. 16; no. 5; p. 1788
• Main Authors: Riethmüller, G, Holz, E, Schlimok, G, Schmiegel, W, Raab, R, Höffken, K, Gruber, R, Funke, I, Pichlmaier, H, Hirche, H, Buggisch, P, Witte, J, Pichlmayr, R
• Format: Journal Article
• Language: English
• Published: United States 01-05-1998
• Subjects: Adenocarcinoma - mortality; Adenocarcinoma - secondary; Adenocarcinoma - surgery; Adenocarcinoma - therapy; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Colorectal Neoplasms - mortality; Colorectal Neoplasms - surgery; Colorectal Neoplasms - therapy; Disease-Free Survival; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Prospective Studies; Survival Rate
• ISSN: 0732-183X
• DOI: 10.1200/jco.1998.16.5.1788

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.
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.
Randomization produced balanced distribution of risk factors. After 7 years of follow-up 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.
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.