Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: A Gynecologic Oncology Group study

Purpose To determine if paclitaxel added to ifosfamide as first-line treatment for advanced uterine carcinosarcoma ( CS) improves overall survival ( OS), progression-free survival (PFS), response, and toxicity. Patients and Methods Eligible patients had measurable stage III or IV, persistent, or recurrent uterine CS. Random assignment to treatment was between ifosfamide 2.0 g/m(2) intravenously ( IV) daily for 3 days ( arm 1) or ifosfamide 1.6 g/m(2) IV daily for 3 days plus paclitaxel 135 mg/m(2) by 3-hour infusion day 1 ( arm 2). Mesna was administered similarly ( both arms); filgrastim began on day 4 ( arm 2). Cycles were repeated every 21 days up to eight cycles. Results Of 214 patients enrolled, 179 were eligible ( arm 1, 91 patients; arm 2, 88 patients). Arm 2 patients experienced more frequent and severe sensory neuropathy ( grade 1 to 4; 8% v 30%). The crude response rate was 29% ( arm 1) and 45% ( arm 2). The odds of response stratified by performance status were 2.21 greater in arm 2 ( P =.017). Median PFS and OS, respectively, for arm 1 compared with arm 2 were 3.6 v 5.8 months and 8.4 v 13.5 months, respectively. There was a 31% decrease in the hazard of death ( hazard ratio [HR], 0.69; 95% CI, 0.49 to 0.97; P =.03) and a 29% decrease in the hazard of progression ( HR, 0.71; 95% CI, 0.51 to 0.97; P =.03) relative to arm 1 when stratifying by performance status. Conclusion OS was significantly improved in arm 2, and toxicities were as expected and manageable. However, the need for active new agents persists, given that OS remains relatively poor in this disease.