Carboplatin versus cisplatin in ovarian cancer

The predominant data from clinical trials of advanced ovarian cancer have documented that carboplatin is equivalent to cisplatin in activity and causes considerably less ototoxicity, neurotoxicity, and nephrotoxicity. A large meta-analysis of over 2,000 patients entered into phase III clinical studies showed that patients with advanced ovarian cancer had virtually identical survival durations when treated with carboplatin- versus cisplatin-containing regimens. Furthermore, in the recent National Institutes of Health Consensus Conference on Ovarian Cancer, it was concluded that "data from mature randomized clinical trials have indicated that the combination of carboplatin and cyclophosphamide is effective therapy" and that "the substitution of carboplatin for cisplatin leads to more acceptable toxicity." Cisplatin appears to be the analog of choice for intraperitoneal therapy, which has proven superior to intravenous (IV) therapy in a recently completed intergroup study. Thus, both analogs are likely to play an important role in therapy of curative intent for patients with stage III, optimal disease. Now that paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has proven to be an essential first-line agent in combination with cisplatin or carboplatin in the management of previously untreated, advanced disease, several new strategies have been developed. In the setting of phase III clinical trials by the Gynecologic Oncology Group (GOG) and the Southwest Oncology Group's (SWOG) Gynecologic Cancer Committee, for example, GOG-114/SWOG-9227 compares the standard IV paclitaxel/cisplatin regimen to a dose-intensive regimen incorporating two courses of carboplatin (area under the concentration-time curve = 9 mg/mL/min) plus intraperitoneal cisplatin/IV paclitaxel. The planned GOG replacement for this study will compare the standard IV paclitaxel (24-hour infusion)/cisplatin regimen to a paclitaxel (3-hour infusion)/carboplatin regimen. In the SWOG, two different high-dose regimens followed by autologous bone marrow transplantation are being evaluated in the setting of a phase II randomized trial. These regimens include high-dose carboplatin/cyclophosphamide/mitoxantrone and high-dose cisplatin/cyclophosphamide/thiotepa. The results of these and other GOG and SWOG trials will dictate the management of advanced ovarian cancer through the end of the century.