PHASE-I RADIOIMMUNOTHERAPY TRIAL WITH IODINE-131-CC49 IN METASTATIC COLON-CARCINOMA

CC49 is a murine monoclonal antibody (MAb) that reacts against the TAG -72 antigen. We carried out a Phase I study with escalating doses of I -131-CC49 in patients with advanced colorectal cancer expressing the T AG-72 antigen to determine the dose-limiting toxicity and therapeutic efficacy, if any, of the radioimmunoconjugate. Methods: Twenty-four pa tients with TAG-72- expressing colorectal cancer were treated with esc alating doses of I-131-CC49 Starting at 15 mCi/m(2) and going up to 90 mCi/m(2) of I-131 labeled to 20 mg MAb CC49. Patients were selected i f TAG-72 was expressed in greater than or equal to 50% of cells in pre viously resected tumor and at least one metastasis was demonstrable on standard imaging such as CT. All patients had failed conventional che motherapy and had not received prior radiotherapy or murine MAb. Patie nts were under radiation isolation precautions until whole-body radioa ctivity decreased to less than or equal to 5 mR/hr at 1 m. Whole-body scintigrams were obtained prior to discharge and 1 and 2 wk after infu sion in all patients. SPECT imaging was carried out at least once in a ll patients. Results: All patients had excellent targeting of radioact ivity to known tumor sites. There was no nonhematologic toxicity. Hema tologic toxicity was more pronounced in those patients who had receive d extensive prior chemotherapy. There were no major responses. All pat ients developed an immune response (HAMA) within 4 wk of therapy. Conc lusion: Radioimmunotherapy with I-131-CC49 is safe and there is signif icant therapeutic efficacy in this Phase I trial at the doses studied. There is excellent targeting of radioactivity to antigen-positive tum ors. Dose-limiting toxicity is hematopoietic, with the maximum tolerat ed dose in this group of heavily pretreated patients being 75 mCi/m(2) .