Irinotecan in epithelial ovarian cancer

Ovarian cancer, the second most common gynecologic malignancy, accounts for approximately 14,000 deaths annually in the United States. Disease relapse after primary treatment, which consists mainly of surgery followed by platinum-based therapy, occurs in more than 60% of ovarian cancer patients overall, and in more than 80% of those diagnosed initially with advanced-stage disease. Responses to second-line chemotherapy agents range from 15% to 25%, and are usually partial responses of short duration. Irinotecan (CPT-11, Camptosar), a camptothecin derivative that inhibits topoisomerase I, is undergoing assessment for the treatment of ovarian cancer. Preclinical studies demonstrated antitumor activity in ovarian cancer. Early phase I or II trials showed response rates of 20% to 25% in patients with recurrent or refractory disease, with some responses noted in the relatively chemoresistant mucinous and clear cell tumors. Irinotecan has also been studied in combination regimens, most commonly irinotecan plus cisplatin. In a phase II trial of irinotecan plus cisplatin in platinum-sensitive or -resistant patients, response rates were 75% and 33%, respectively. Irinotecan seems to be relatively well tolerated; dose-limiting toxicities appear to be diarrhea, nausea and vomiting, and leukopenia/neutropenia.