Enhanced antitumor activity of combination radioimmunotherapy (I-131-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 I-131-labeled mAb A33 (I-131-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 I-131-mAb A33 (0.1 mCi) and chemotherapy [5-fluorouracil (5-FU) or 5-FU + leucovorin, doxorubicin, or carmustine] enhance the antitumor effects, compared to I-131-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/dag 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 I-131-mAb A33 showed a statistically significant additive antitumor effect compared to I-131-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 I-131-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 radiolabelled antibody therapy with 5-FU-based treatments are warranted.