A PHASE-I TRIAL OF A RHENIUM 186-LABELED MONOCLONAL-ANTIBODY ADMINISTERED INTRAPERITONEALLY IN OVARIAN-CARCINOMA - TOXICITY AND CLINICAL-RESPONSE

Objectives: To determine the maximum tolerated dose, spectrum of toxic ity, and response of persistent and recurrent ovarian carcinoma to int raperitoneal injection of a conjugate of rhenium 186 (Re-186) and a mo noclonal antibody; to measure the radiation distribution to normal str uctures; and to establish the fate of the infused isotope. Methods: Rh enium 186 was conjugated to murine monoclonal antibody NR-LU-10, which binds to a cell surface antigen present on ovarian carcinoma. In a do se-escalating phase I trial, a single dose of 25 mg/m2 of antibody com plexed with 25-150 mCi/m2 of Re-186 was administered intraperitoneally to 17 women with ovarian carcinoma that was recurrent or persistent a fter platinum-based chemotherapy. Results: Severe myelosuppression was observed at 150 mCi/m2 of Re-186 in two evaluable patients. Other cli nically significant toxicities included low-grade fever and transient skin rash. Hepatic enzyme elevation was seen in 12 of 17 patients, but was not clinically significant. No chronic enteric toxicity was obser ved. Decreased tumor size was demonstrated by repeat operation in four of seven patients with disease measuring less than 1 cm at the time o f treatment (four of 17 total). All four responders had serum CA 125 l evels of 35 U/mL or less at the time of treatment and had received onl y one regimen of chemotherapy. Conclusion: This immunoconjugate can be administered intraperitoneally with acceptable toxicity and produces objective responses after a single dose in patients with minimal objec tive disease.