Salvage chemotherapy for epithelial ovarian carcinoma

Advanced epithelial ovarian cancer is a highly chemosensitive solid tumor with response rates of 70-80% to first-line chemotherapy, including a high proportion of complete responses. The majority of patients, however, eventually relapse and ultimately die of chemoresistant disease. Response rates to salvage agents are modest, and duration of response is relatively short. Important new agents have been identified in the salvage setting, however, and all patients with ovarian cancer recurring or persisting after front-line therapy should be encouraged to enroll in clinical trials. Phase II trials should include multiple adequately sized cohorts, for patients with platinum-sensitive disease and those with platinum-refractory disease. In addition, patients should be stratified by treatment-free interval. An effort should be made to report standard response endpoints, such as median duration of response, median time to progression, and median survival. Retreatment with a platinum-containing compound is appropriate in patients with platinum-sensitive disease. Trials of high-dose chemotherapy with hematologic support may be most appropriate for patients with minimal disease following first-line therapy, but are unlikely to benefit patients with platinum-resistant or bulky disease. Paclitaxel should figure prominently in consideration of salvage therapy for patients with platinum-resistant disease. Responses to other single agents or combination chemotherapy have been modest and generally of short duration. Efforts at hormonal therapy have been disappointing. Promising new agents include topoisomerase I inhibitors, such as topotecan, 9-aminocamptothecin, irinotecan (CPT-11), and pyrazoloacridine. Therapies focusing on novel molecular targets include antiangiogenesis agents, antimetastatic agents, and signal transduction inhibitors. Immunotherapy, including radioimmunotherapy, immunotoxins, and direct antitumor effects of monoclonal antibodies, may be useful. Greater understanding of the molecular pathology of ovarian cancer may help us develop more rational and effective treatment.