Intraperitoneal radioimmunochemotherapy of ovarian cancer: A phase I study

A phase I trial was designed to examine the feasibility of combining interf eron and Taxol with intraperitoneal radioimmunotherapy (Lu-177-CC49). Patie nts with recurrent or persistent ovarian cancer confined to the abdominal c avity after first line therapy, Karnofsky, performance status > 60, adequat e liver, renal and hematologic function, and tumor that reacted with CC49 a ntibody were enrolled. Human recombinant alpha interferon (IFN) was adminis tered as 4 subcutaneous injections of 3 X 10(6) U on alternate days beginni ng 5 days before RIT to increase the expression of the tumor-associated ant igen, TAG-72. The addition of IFN increased hematologic toxicity such that the maximum tolerated dose (MTD) of the combination was 40 mCi/m(2) compare d to Lu-177-CC49 alone (45 mCi/m(2)). Taxol, which has radiosensitizing eff ects as well as antitumor activity against ovarian cancer, was given intrap eritoneally (IP) 48 hrs before RIT. It was initiated at 25 mg/m(2) and esca lated at 25 mg/m(2) increments to 100 mg/m(2). Subsequent groups of patient s were treated with IFN + 100 mg/m(2) Ta-vol + escalating doses of Lu-177-C C49. Three or more patients were treated in each dose group and 34 patients were treated with the 3-agent combination. Therapy was well tolerated with the expected reversible hematologic toxicity. The MTD for Lu-177-CC49 was 40 mCi/m(2) when given with IFN + 100 mg/m(2) Taxol. Interferon increased t he effective whole body half-time of radioactivity and the whole body radia tion dose. Taxol did not have a significant effect on pharmacokinetic or do simetry, parameters. Four of 17 patients with CT measurable disease had a p artial response (PR) and 4 of 27 patients with non-measurable disease have Progression-free intervals of 18+, 21+, 21+, and 37+ months. The combination of intraperitoneal Taxol chemotherapy (100 mg/m(2)) with RI T using Lu-177-CC49 and interferon was well tolerated, with bone marrow sup pression as the dose-limiting toxicity.