Enhanced antitumor activity of combination radioimmunotherapy (131I-labeled monoclonal antibody A33) with chemotherapy (fluorouracil).
Monoclonal antibody (mAb) A33 reacts with an antigen expressed by >95% of colon cancer and normal colon epithelial cells. An earlier Phase I trial of 131I-labeled mAb A33 (131I-mAb A33) demonstrated bone marrow suppression as the dose-limiting toxicity, and although modest antitumor effects were seen, no normal colon toxicity was observed. In this study, a nude mouse model was used to test whether combinations of low-dose 131I-mAb A33 (0.1 mCi) and chemotherapy [5-fluorouracil (5-FU) or 5-FU + leucovorin, doxorubicin, or carmustine] enhance the antitumor effects, compared to 131I-mAb A33 alone or either drug regimen alone. 5-FU was administered either at 30 mg/kg/day for 5 days or at 75 mg/kg/day on days 1 and 5. In assessing the reduction in tumor volumes over the first 28 days of the experiment, 5-FU treatment (with or without leucovorin) in combination with 131I-mAb A33 showed a statistically significant additive antitumor effect compared to 131I-mAb A33 alone or to chemotherapy alone. When long-term survival was used as an end point, 38% of the mice treated with 5-FU and 131I-mAb A33 were disease free at 276 days compared to none from any other group, suggesting a synergistic effect. These data indicate that Phase II clinical trials combining radiolabeled antibody therapy with 5-FU-based treatments are warranted.