Despite the progress in detection and therapy, epithelial ovarian cancer (EOC) remains a public health problem of the highest order. The survival rate for advanced stages of this cancer is low. Innovative strategies need to be sought and tested to enhance therapeutic efficacy of conventional chemotherapy for EOC. Radioimmunotherapy (RAIT) has been applied to advanced EOC in multiple phase I/II studies, to date only with non- myeloablative doses. These results, though early, show response rates that are higher than with RAIT of most other solid tumors. Preclinically and clinically it has been shown that concurrent radiation and chemotherapy can enhance each other's anti-tumor effects with manageable side effects. It is also apparent, both from preclinical work and initial phase I data, that RAIT and chemotherapy can also have additive or synergistic anti-tumor effects, without much greater toxicities, without much greater toxicities than are seen with either modality alone. Because of the growing amount of positive preclinical data regarding the combination of RAIT and chemotherapy and because of the encourage initial phase I results in allogeneic BMT for acute myelogenous leukemia, we consider it critically important to test this innovative combination in this serious cancer problem. We will test specifically the hypothesis that advanced EOC can be treated with high doses of a radiolabeled anti-CEA monoclonal antibody, hMN14 either alone or combined with standard dose chemotherapy. This project is linked to simultaneous clinical and preclinical efforts to identify other, potentially more efficacious, RAIT agents for EOC. Such data, if positive, will then be applied to this general therapeutic approach.
