RANDOMIZED TRIAL OF MONOCLONAL-ANTIBODY FOR ADJUVANT THERAPY OF RESECTED DUKES-C COLORECTAL-CARCINOMA

Over the past decade various clinical trials have used monoclonal anti bodies as therapeutic agents against solid tumours. No consistent patt ern of response or improved survival has yet emerged although antigeni c heterogeneity and insufficient accessibility of cells in advanced tu mours have been offered as explanations for these failures. We designe d a study in which a monoclonal antibody was used to target minimal re sidual disease in an early stage of tumour cell dissemination in patie nts with colorectal cancer. Only patients in Dukes' stage C who had un dergone curative surgery and were free of manifest residual tumour wer e admitted. 189 patients with colorectal cancer of stage Dukes' C were randomly assigned to an observation regimen or to postoperative treat ment with 500 mg of 17-1A antibody, followed by four 100 mg infusions each month. A balance of risk factors in the two groups was achieved b y dynamic randomisation procedure. After a median follow-up of 5 years , antibody treatment reduced the overall death rate by 30% (Cox's prop ortional hazard, p = 0.04, log-rank p = 0.05) and decreased the recurr ence rate by 27% (p = 0.03, p = 0.05). The effect of antibody was most pronounced in patients who had distant metastasis as first sign of a relapse (p = 0.0014, p = 0.002), an effect that was not seen for local relapses (p = 0.74, p = 0.67). Toxic effects of 17-1A antibody were i nfrequent, consisting mainly of mild constitutional and gastrointestin al symptoms. During 371 infusions four anaphylactic reactions were see n, all controllable by intravenous steroids and none necessitated admi ssion to hospital. Adjuvant therapy with 17-1A antibody extends life a nd prolongs remission in patients with colorectal cancer of Dukes' sta ge C.