New options for the treatment of advanced ovarian cancer.

Over the last decade, platinum-based combination chemotherapy regimens have led to higher response rates and longer survival for advanced ovarian cancer patients than previous regimens based on alkylating agents. The advent of paclitaxel for salvage therapy and, more recently, as a component of first-line treatment in advanced disease has further improved response rates and prolonged survival. Nonetheless, even with current treatments, relapse rates remain high and most women with advanced ovarian cancer ultimately will die of their disease. For this reason, the development of new, effective second-line treatments, as well as better first-line agents, for advanced disease remains a high priority. To maximize the efficacy of second- or third-line drugs, new agents should be non-cross-resistant with platinum or paclitaxel. Chemotherapy drugs for advanced ovarian cancer with novel mechanisms of action include topotecan (Hycamtin; SmithKline Beecham Pharmaceuticals, Philadelphia, PA), a topoisomerase I inhibitor. Topotecan was recently shown to be effective in platinum-refractory or -resistant patients, with response rates ranging from 14% to 23%. Results from a phase III clinical study indicate that topotecan compares favorably with paclitaxel as a second-line treatment for stage III and IV patients who have failed platinum-based regimens. Moreover, a phase II study demonstrated clinical responses with topotecan in patients who had failed both paclitaxel- and platinum-based therapies. Other agents for advanced ovarian cancer are also under investigation, including docetaxel, oral etoposide, liposome encapsulated doxorubicin, gemcitabine, ifosfamide, and hexymethylmelamine.