Abstract

In patients with advanced ovarian cancer, high response rates are achieved with chemotherapy combinations that include alkylating agents and platinum coordination complexes. However, few patients experience long-term control of disease, especially when primary resection leaves substantial residual mass. Paclitaxel (Taxol®), a new agent with documented activity in platinum-refractory ovarian cancer, has been shown to be well tolerated when given in combination with cisplatin. In this prospective study, we compared the combination of paclitaxel-cisplatin with a standard therapy of cyclophosphamide-cisplatin in patients with suboptimal stage III and stage IV disease. Of 410 patients with advanced ovarian cancer and <1-cm residual masses following initial surgery, 386 met all eligibility criteria. These patients were randomly assigned to receive a regimen of cisplatin (75 mg m^-2) and cyclophosphamide (750 mg m^-2) or cisplatin (75 mg m^-2) and paclitaxel (135 mg m^-2) delivered over 24 h. Dosage reductions in cyclophosphamide or paclitaxel were permitted for significant toxicity. Among 216 patients with measurable disease, responses were reported in 73% of those randomized to receive cisplatin-paclitaxel and in 60% of those who received cisplatin-cyclophosphamide. Median progression-free survival was significantly longer (P<0.001) with the cisplatin-paclitaxel combination compared with cisplatin-cyclophosphamide (17.9 vs 12.9 months, respectively). Median overall survival also was significantly longer (P < 0.001) with cisplatin-paclitaxel (37.5 vs 24.4 months). Thus, this study provides compelling evidence that giving the paclitaxel-cisplatin combination as first-line therapy for suboptimally debulked stage III or any stage IV ovarian cancer can increase both the duration of the progression-free interval and the overall survival while maintaining an acceptable toxicity profile.