Prolonged oral etoposide as second-line therapy for platinum-resistant and platinum-sensitive ovarian carcinoma: A gynecologic oncology group study

Purpose: A phase II trial was conducted to determine the activity of prolonged oral etoposide in platinum resistant and platinum-sensitive ovarian carcinoma. Patients and Methods: platinum-resistant disease was defined as progression on platinum-based chemotherapy or recurrence within 6 months of completing therapy. The starting dose was 50 mg/m(2)/d (30 mg/m(2)/d for prior radiotherapy) for 21 days, every 28 days. A dose escalation to a maximum dose of 60 mg/m(2)/d was prescribed. Results: Of 99 patients entered, 97 were assessable for toxicity and 82 were assessable for response. Among 41 platinum-resistant patients a 26.8% response rate (7.3% complete response [CR] and 19.5% partial response [PR] rate) occurred. The median response duration was 4.3 months (range, 1.3 to 8.7), median progression-free interval (PFI) was 5.7 months (range, 0.8 to 30.8+), and median survival time was 10.8 months (range, 1.9 to 45.8). Twenty five of 41 platinum-resistant patients had also previously received paclitaxel; of which eight (32%) responded. Among 41 platinum-sensitive patients, a 34.1% response rate (14.6% CR and 19.5% PR rate) occurred. The median response duration was 7.5 months (range, 1.9 to 15.2+), median PFI was 6.3+ months (range, 0.9 to 20.4), and median survival time was 16.5+ months (range, 0.9 to 34.8). Of 97 patients assessable For toxicity, grade 3 or 4 hematologic toxicity was common, with leukopenia occurring in 41.2% (grade 3, 29%; grade 4, 12%), neutropenia in 45.4% (grade 3, 20%; grade 4, 25%), thrombocytopenia in 9% (grade 3, 5%; grade 4, 4%), and anemia in 13.4%. Three treatment-related deaths occurred: two from neutropenic sepsis and one from thrombocytopenic bleeding after an overdose. One patient developed leukemia. Conclusion: This regimen is active in platinum-resistant and platinum-sensitive ovarian carcinoma. Additionally, the regimen is active in paclitaxel-resistant ovarian carcinoma. (C) 1998 by American Society of Clinical Oncology.