INTRAPERITONEAL RECOMBINANT ALPHA-INTERFERON FOR SALVAGE IMMUNOTHERAPY IN STAGE-III EPITHELIAL OVARIAN-CANCER - A GYNECOLOGIC ONCOLOGY GROUP-STUDY

Abstract

Fourteen patients with persistent epithelial ovarian cancer documented at second look laparotomy after combination chemotherapy were treated with 146 cycles of .alpha.-recombinant interferon (rIFN-.alpha.2) administered i.p. The initial dose was 5 .times. 106 units which was escalated weekly to 50 .times. 106 units over 4 weeks and then continued weekly for a total of 16 weeks. Eleven patients underwent surgical reevaluation after therapy which confirmed four pathological complete responses (36%), one partial response (9%), and disease progression in six patients (55%). Five of seven patients (71%) with residual tumor < 5 mm had a surgically documented response, whereas there was no response in the four patients whose tumors were .gtoreq. 5 mm. Three patients were evaluable for clinical response only; one patient who refused surgery had a complete clinical response with total resolution of ascites; one had stable disease; and one had disease progression. Fever .gtoreq. 38.degree. C was seen in 58%, fever .gtoreq. 39.0.degree. C was seen in 18%, vomiting in 37%, abdominal pain was reported in 22%, and one patient had infectious peritonitis. Peripheral white blood cell counts and i.p. washings were obtained pretreatment and on days 1, 3, and 7 after treatment. While there was no consistent alteration in peripheral white blood cell counts, the numbers of i.p. monocytes and lymphocytes showed a significant boost on day 1 after each dose of rIFn-.alpha.2. Natural killer lymphocyte cytotoxicity was elevated in the i.p. cavity fluid otained from most patients on day 1 after treatment, while blood natural killer lymphocyte cytotoxicity values showed considerable variability. Pharmacokinetic studies show that i.p. levels of rIFN-.alpha.2 were 30-1000 times blood levels. rIFN-.alpha.2 i.p. may act by increasing concentrations of drug and augmenting regional host cells in patients with minimal residual ovarian cancer.