PILOT RADIOIMMUNOTHERAPY TRIAL WITH I-131-LABELED MURINE MONOCLONAL-ANTIBODY CC49 AND DEOXYSPERGUALIN IN METASTATIC COLON-CARCINOMA

An antimouse immune response is invariable following administration of murine monoclonal antibody (mAb), precluding effective multidose ther apy, In advanced colorectal cancer patients, we carried out a pilot st udy with multiple doses of I-131-labeled CC49 administered with deoxys pergualin (DSG), an immunomodulator, to determine its effect on immune response, Cumulative toxicity and efficacy were also evaluated. Six p atients with tumor-associated glycoprotein 72-expressing colorectal ca ncer were treated i.v. with 15 mCi/m(2) I-131-labeled to 20 mg mAb CC4 9 biweekly, along with concurrent DSG 200 mg/m(2) daily for 5 days, fo r a maximum of four courses, None had received prior murine mAbs. All patients had targeting of radioactivity to known tumor sites following initial infusion, Four of six patients received all four courses of t herapy, three, without any acute side effects, In these patients, ther e was no change in serum clearance with variable tumor targeting follo wing repeat infusions, Two patients had less than or equal to grade II anaphylactoid reactions, which were treated without sequelae. One of these had faster serum clearance of radioactivity following repeat inf usions of I-131-labeled CC49, Human antimouse antibody titers in all p atients were significantly less compared to concurrent times in patien ts receiving CC49 without DSG (P < 0.05), There was no correlation bet ween the human antimouse antibody titer and serum clearance or tumor t argeting of I-131-labeled CC49, There were no clinical responses. We c oncluded that multiple doses of murine antibody I-131-labeled CC49 can be safely administered with no change in serum or whole-body kinetics in 50% of patients treated biweekly, DSG may reduce the human immune response to the murine mAb.