Chemotherapy for advanced ovarian cancer: overview of randomized trials

Until the mid-1970s, standard therapy for ovarian carcinoma was a single alkylating agent. Subsequently, combination chemotherapy was shown to be superior to such therapy. During the 1980s, cisplatin-based combination chemotherapy became the standard chemotherapy regimen for advanced ovarian cancer; however, other classes of agents with documented activity against ovarian tumors appeared to be cross-resistant with platinum. The introduction of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the early 1990s, with its apparent lack of cross-resistance with platinum compounds, was a notable advance in ovarian cancer management that dramatically altered the standard of care. During the 1990s, the combination of platinum (cisplatin or carboplatin) plus paclitaxel rapidly evolved into front-line chemotherapy for advanced ovarian cancer. The series of randomized phase III studies that have compared the activity of platinum/paclitaxel with alternative regimens, including the previous standard combination of cisplatin/cyclophosphamide, support the combination of platinum/paclitaxel as the current standard chemotherapy for advanced ovarian cancer. Outstanding issues that stem from this phase III experience include the impact of nonprotocol salvage regimens on survival and the potential benefits of sequential single-agent regimens.