A phase I study of intraperitoneal interferon-alpha 2b and intravenous cis-platinum 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 activity against epithelial ovarian cancer. The objective of this study was to determine the maximum tolerated dose of intraperitoneal (ip) IFN-alpha 2b which could be administered in combination with intravenous (iv) cis-platinum plus cyclophosphamide chemotherapy. After comprehensive surgical staging and maximal cytoreduction, previously untreated patients with primary ovarian adenocarcinoma were entered at one of five IFN dose levels. IFN-alpha 2b (5-30 x 10(6) units) was administered ip on Day 1 (+/- Day 8). cis-Platinum (75 mg/m2) plus cyclophosphamide (750 mg/m2) were administered iv on Day 2 with prophylactic hydration and anti-emetics. Courses were repeated every 3 weeks for 8 cycles. 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 cycles. Catheter-related complications occurred in 8 patients, and in three cases lead to catheter removal and discontinuation of ip therapy. Two patients experienced grade 2-3 nephrotoxicity and 1 experienced grade 2 peripheral neuropathy. There was a single episode of chemical peritonitis. 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 interruption or dose reduction. Planned cis-platinum dose intensity was most compromised at the fifth IFN-alpha 2b dose level. The maximum tolerated dose of IFN-alpha 2b was determined to be 20 x 10(6) units repeated on Days 1 and 8 of this 21-day cis-platinum plus cyclophosphamide chemotherapy cycle.