PHASE-II RADIOIMMUNOTHERAPY TRIAL WITH I-131 CC49 IN COLORECTAL-CANCER

Background. Radiolabeled CC49, a second generation high affinity monoc lonal antibody (MoAb) reactive with tumor-associated glycoprotein 72 ( TAG72) has undergone previous Phase I testing in patients with colon c ancer. Based on this report, the authors treated 15 refractory metasta tic colon cancer patients with I-131-CC49 to determine its overall tox icity and the response to therapy of patients treated with it. Methods . Patients received 75 mCi/m(2 131) I-CC49 (20 mg MoAb) intravenously for a period of 30-60 minutes. Whole body retention was derived from t he measured dose-rate of I-131 monitored daily at 1 m using an ion cha mber. Two whole-body and static-gamma camera images were taken of pati ents on days 4 and 7 after the infusion. Results. Nonhematologic toxic ity (Grade 1-2) consisted of nausea (two patients), arthralgias (three patients), transient fever and chills (two patients), and transient b lood pressure changes (two patients). At 4-5 weeks posttreatment, reve rsible Grade 3-4 thrombocytopenia was observed in 7 of 15 patients, an d reversible Grade 3-4 granulocytopenia was observed in 6 of 15 patien ts. Twelve of 13 patients tested developed human antimouse antibody (r ange, 161 to >20,000 ng/ml) at 6-8 weeks postinfusion. Mean +/- SD who le-body half-life (whole-body retention) of I-131-CC49 was 57.3 +/- 13 .4 hours. Tumors were seen in all patients. In two of three patients t reated a second time, an increased whole body clearance rate correlate d with elevated human antimouse antibody, reduced uptake in tumor, and enhanced uptake in the thyroid. Estimated tumor doses ranged from 19- 667 rads. Red marrow dose estimated from whole body retention ranged f rom 60 to 117 rads and correlated with decreases in platelet count. No objective tumor responses (i.e., partial or complete) were observed. Conclusions. Despite minimal toxicity and favorable tumor uptake, effi cacy has been limited at this dose and schedule. Cancer 1994; 73:1057- 66.