ESCALATING PROTEIN DOSES OF CHIMERIC MONOCLONAL-ANTIBODY MOV18 IMMUNOGLOBULIN-G IN OVARIAN-CARCINOMA PATIENTS - A PHASE-I STUDY

BACKGROUND, Successful first-line treatment of ovarian cancer does not incite cure. Recurrent disease often shows an increased resistance to chemotherapeutic agents. Therefore, other treatment modalities, like (radio)immunotherapy using tumor-associated monoclonal antibodies, sho uld be considered. Chimeric MOv18 (c-MOv18) localizes welt in ovarian carcinoma tissue. We investigated the safety of a single intravenous ( i.v.) infusion of increasing doses of c-MOv18 in ovarian carcinoma pat ients. METHODS, Fifteen patients received c-MOv18 (from 5 mg to 75 mg) . Safety was determined by recording vital signs; by hematological, bi ochemical, and urinary analyses; and by the human-antichimeric antibod y (HACA) response. Five patients received c-MOv18 labeled with a trace r dose of iodine-131 to analyze the pharmacokinetics and biodistributi on in blood, urine, and tissue biopsies at surgery. RESULTS, Administr ation of c-MOv18 IgG was uneventful. No significant changes in hematol ogical, biochemical, or urine profiles were noted at any time postinje ction (p.i). Starting with a dose of 50 mg, all patients experienced s ide effects, like fever, headache, and nausea/vomiting, maximally Grad e II (World Health Organization toxicity scale). No HACA response was found up to 12 weeks p.i. The mean elimination half-life after infusio n of 30-75 mg c-MOv18 was significantly higher compared with infusion of 1 mg. Absolute amount of c-MOv18 in carcinoma tissue increased with increasing c-MOv18 doses. CONCLUSIONS, Intravenous administration of c-MOv18 IgG in a dose up to 75 mg is safe, inducing only minor side ef fects at doses of 50 mg or higher. In view of the characteristics of c -MOv18, this antibody might be applicable as an unmodified antibody or as an immunoconjugate in the treatment of ovarian carcinomas. (C) 199 7 American Cancer Society.