Advanced ovarian cancer: a clinical update on first-line treatment, recurrent disease, and new agents

Platinum-based therapy plays an integral role in the first-line treatment of advanced ovarian cancer as well as in the recurrent disease setting. In advanced disease, the standard of care in the United States is maximal surgical cytoreduction followed by paclitaxel/carboplatin chemotherapy. Results from the Gynecologic Oncology Group COG 158 trial show that paclitaxel/carboplatin is at least as effective as paclitaxel/cisplatin and is better tolerated and easier to administer. Three randomized phase III trials suggest that intraperitoneal chemotherapy may provide superior progression-free or overall survival relative to systemic chemotherapy, but at the price of increased toxicity. Results from COG 178 showed that prolonged maintenance paclitaxel therapy improved progression-free survival of patients with clinical complete responses to first-line chemotherapy. The ongoing COG 182 protocol for advanced ovarian cancer is comparing 8 cycles of paclitaxel/carboplatin with 4 experimental combinations incorporating topotecan, gemcitabine, or encapsulated doxorubicin. Currently, no randomized GOG trial evaluates maintenance or intraperitoneal therapy for advanced disease. With recurrent disease, a treatment-free interval of more than 6 months is an important predictor of platinum sensitivity. In this setting, carboplatin has been the cornerstone of treatment. Recent results from the International Collaborative Ovarian Neoplasm ICON 4 trial indicate that paclitaxel/carboplatin may offer superior efficacy to single-agent carboplatin. Additional randomized comparisons of carboplatin versus other carboplatin combinations are in progress. Finally, a variety of new cytotoxic and biologic agents are being evaluated in recurrent disease, either as single agents or in combination with standard chemotherapy.