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 marr ow suppression as the dose-limiting toxicity, and although modest anti tumor effects were seen, no normal colon toxicity was observed, In thi s study, a nude mouse model was used to test whether combinations of l ow-dose I-131-mAb A33 (0.1 mCi) and chemotherapy [5-fluorouracil (5-FU ) or 5-FU + leucovorin, doxorubicin, or carmustine] enhance the antitu mor effects, compared to I-131-mAb A33 alone or either drug regimen al one, 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 wit hout leucovorin) in combination with I-131-mAb A33 showed a statistica lly significant additive antitumor effect compared to I-131-mAb A33 al one or to chemotherapy alone, When long-term survival was used as an e nd point, 38% of the mice treated with 5-FU and I-131-mAb A33 were dis ease free at 276 days compared to none from any other group, suggestin g a synergistic effect, These data indicate that Phase II clinical tri als combining radiolabelled antibody therapy with 5-FU-based treatment s are warranted.