title: Monoclonal antibody therapy for resected Dukes' C colorectal cancer: seven-year outcome of a multicenter randomized trial.
abstract: OBJECTIVE
  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.
  
  
  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-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institut für Immunologie, Ludwig-Maximilians-Universität München, Germany. riethmueller@ifi.med.uni_muenchen.de
authors.forename: G
authors.initials: G
authors.lastname: Riethmüller
authors.forename: E
authors.initials: E
authors.lastname: Holz
authors.forename: G
authors.initials: G
authors.lastname: Schlimok
authors.forename: W
authors.initials: W
authors.lastname: Schmiegel
authors.forename: R
authors.initials: R
authors.lastname: Raab
authors.forename: K
authors.initials: K
authors.lastname: Höffken
authors.forename: R
authors.initials: R
authors.lastname: Gruber
authors.forename: I
authors.initials: I
authors.lastname: Funke
authors.forename: H
authors.initials: H
authors.lastname: Pichlmaier
authors.forename: H
authors.initials: H
authors.lastname: Hirche
authors.forename: P
authors.initials: P
authors.lastname: Buggisch
authors.forename: J
authors.initials: J
authors.lastname: Witte
authors.forename: R
authors.initials: R
authors.lastname: Pichlmayr
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000556:secondary / Q000601:surgery / Q000628:therapy*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000401:mortality / Q000601:surgery / Q000628:therapy*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal