Phase III randomized study of cisplatin versus paclitaxel versus cisplatinand paclitaxel in patients with suboptimal stage III or IV ovarian cancer:A gynecologic oncology group study

Purpose: To assess progression-free survival (PFS) and overall survival (OS ) in patients with suboptimally debulked epithelial ovarian cancer receivin g cisplatin (100 mg/m(2)) or 24-hour infusion paclitaxel (200 mg/m(2)) or t he combination of paclitaxel (135 mg/m(2)) followed by cisplatin (75 mg/m(2 )). Patients and Methods: After stratification for disease measurability, patie nts were randomized to receive six cycles of one of the treatments every 3 weeks. If measurable, complete response (CR) or partial response (PR) was d etermined. Results: Six hundred fourteen of 648 patients who entered onto the trial we re eligible. Monotherapies were discontinued more frequently (cisplatin bec ause of toxicity or patient refusal [17%], and paclitaxel because of progre ssion [20%]) compared with the combination therapy (7% and 6%, respectively ). Neutropenia, fever, and alopecia were more severe with paclitaxel-contai ning regimens; whereas anemia, thrombocytopenia, neurotoxicity, nephrotoxic ity, and gastrointestinal toxicity were more severe with cisplatin-containi ng regimens. The CR/PR rates on paclitaxel monotherapy were significantly l ower compared with the cisplatin regimens (42% v 67%, respectively; P < .00 1), The relative hazard (RH) of first progression or death was significantl y greater among those randomized to paclitaxel (RH = 1.41; 95% confidence i nterval [CI], 1.15 to 1.73; P < .001)when compared with cisplatin; however, RH did not differ significantly between the two cisplatin regimens (RH = 1 .06; 95% CI, 0.895 to 1.30). Relative to cisplatin, the death rate on pacli taxel was 15% greater (RH = 1.15; 95% CI, 0.929 to 1.42), and the death rat e on the combination treatment was 1% less (RH = 0.99: 95% CI, 0.795 to 1.2 3). These differences among treatment groups were not statistically signifi cant (P = .31). Conclusion: Cisplatin alone or in combination yielded superior response rat es and PFS relative to paclitaxel. However, OS was similar in all three arm s, and the combination therapy had ct better toxicity profile. Therefore, t he combination of cisplatin and paclitaxel remains the preferred initial tr eatment option. (C) 2000 by American Society of Clinical Oncology.