A PHASE-I STUDY OF INTRAPERITONEAL INTERFERON-ALPHA(2B) AND INTRAVENOUS CISPLATINUM PLUS CYCLOPHOSPHAMIDE CHEMOTHERAPY IN PATIENTS WITH UNTREATED STAGE-III EPITHELIAL OVARIAN-CANCER - A GYNECOLOGIC-ONCOLOGY-GROUP PILOT-STUDY

Previous clinical investigations using interferons (IFNs) have shown a ctivity against epithelial ovarian cancer, The objective of this study was to determine the maximum tolerated dose of intraperitoneal (ip) I FN-alpha(2b) which could be administered in combination with intraveno us (iv) cis-platinum plus cyclophosphamide chemotherapy, After compreh ensive surgical staging and maximal cytoreduction, previously untreate d patients with primary ovarian adenocarcinoma were entered at one of five IFN dose levels, IFN-alpha(2b) (5-30 x 10(6) units) was administe red ip on Day 1 (+/-Day 8). cis-Platinum (75 mg/m(2)) plus cyclophosph amide (750 mg/m(2)) were administered iv on Day 2 with prophylactic hy dration and antiemetics, Courses were repeated every 3 weeks for 8 cyc les, Adverse effects were recorded using standard Gynecologic Oncology Group toxicity scales, Fifteen patients with mean age 56 years (range 43-73) were entered and received a combined total of 100 treatment cy cles, Catheter-related complications occurred in 8 patients, and in th ree cases lead to catheter removal and discontinuation of ip therapy, Two patients experienced grade 2-3 nephrotoxicity and 1 experienced gr ade 2 peripheral neuropathy, There was a single episode of chemical pe ritonitis. Myelosuppression was the dose-limiting toxicity with grade 3-4 leukopenia complicating 6, 5, 12, 11, and 17 cycles at dose levels 1-5, respectively, No patient completed planned treatment without int erruption or dose reduction, Planned cis-platinum dose intensity was m ost compromised at the fifth IFN-alpha(2b) dose level, The maximum tol erated dose of IFN-alpha(2b) was determined to be 20 x 10(6) units rep eated on Days 1 and 8 of this 21-day cis-platinum plus cyclophosphamid e chemotherapy cycle. (C) 1995 Academic Press, Inc.