PROSPECTS OF RADIOIMMUNOTHERAPY IN EPITHELIAL OVARIAN-CANCER - RESULTS WITH IODINE-131-LABELED MURINE AND HUMANIZED MN-14 ANTICARCINOEMBRYONIC ANTIGEN MONOCLONAL-ANTIBODIES

Objectives. Epithelial ovarian cancer (EOC) is known to produce carcin oembryonic antigen (CEA), and the plasma CEA level is frequently eleva ted in patients with advanced stage and bulk of tumor. This study repo rts the results of a phase I therapy trial with intravenously administ ered I-131-MN-14 anti-CEA monoclonal antibody (MAb) in patients with E OC. Methods. Fourteen patients with advanced refractory EOC were given escalating intravenous doses (two received 30 mCi/m(2), six 40 mCi/m( 2), and six 50 mCi/m(2)) of I-131-MN-14 IgG. All patients received a d iagnostic study with 8 mCi (0.6 mg) of I-131-MN-14 IgG 1 week prior to their therapy infusion. Tumor targeting was assessed by external scin tigraphy, toxicity according to the Radiation Therapy Oncology Group c riteria, and therapy responses by CT and serum CA-125. Results. The MA b scan was positive in all 14 treated patients. Myelosuppression was t he only observed treatment-related toxicity. Dose-limiting toxicity, d efined as grade 4 leukopenia or thrombocytopenia of any duration, or g rade 3 leukopenia or thrombocytopenia of > 2 weeks, was not seen at th e 30 or 40 mCi/m(2) dose levels. However, 2 of 6 patients treated at 5 0 mCi/m(2) had a grade 4 thrombocytopenia or a grade 3 thrombocytopeni a lasting 18 days. Of the 14 patients, 1 with diffuse peritoneal impla nts of less than or equal to 2 cm had a complete clinical remission by CT and CA-125 for 8 months, following an initial partial remission fo r 10 months, both at the 40 mCi/m(2) dose level, Another patient had a mixed response for 1 month. Conclusion. MN-14 anti-CEA MAb is a suita ble agent for tumor targeting and may have a therapeutic potential in patients with chemotherapy-refractive EOC, especially those with minim al disease. (C) 1997 Academic Press.