Ifosfamide, paclitaxel and cisplatin first-line chemotherapy in advanced, suboptimally debulked epithelial ovarian cancer

BACKGROUND. The combination of paclitaxel with a platinum analogue is the p referred chemotherapy regimen in the treatment of advanced epithelial ovari an carcinoma. The alkylating agent ifosfamide has shown activity in refract ory or recurrent ovarian cancer. We conducted a Phase II study with the com bination of ifosfamide, paclitaxel, and cisplatin for the treatment of newl y diagnosed patients with advanced, suboptimally debulked ovarian carcinoma . METHODS. Thirty-five consecutive patients with advanced ovarian carcinoma ( International Federation of Gynecology and Obstetrics [FIGO] Stage III or I V) and residual disease larger than 2 cm after staging laparotomy and cytor eductive surgery were treated with paclitaxel, 175 mg/m(2), as a 3-hour int ravenous infusion on Day 1, cisplatin 75 mg/m2 intravenously over 2 hours o n Day 2, and ifosfamide 1500 mg/m2 intravenously over I hour on Days 1-3 (w ith sodium 2-mercaptoethone sulfonate [MESNA] uroprotection). Courses were administered every 3 weeks on an outpatient basis. Granulocyte-colony stimu lating factor was given at a dose of 5 mug/kg/day on Days 7-11. RESULTS. Among 26 patients with measurable disease, 22 (85%) achieved an ob jective response including 15 complete and 7 partial responses. With a mini mum follow-up of 46 months, the median overall survival was 52.8 months (ra nge, 5.3-56.6+ mos), whereas the median time to progression for all patient s was 22.2 months. The median remission duration for women with measurable disease who responded to treatment was 12.6 months. The treatment was toler ated relatively well without toxic deaths; the most common toxicity was Gra de 3 or 4 neutropenia that occurred in 42% of patients. Significant periphe ral neuropathy (Grade 2 or higher) developed in 35% of patients. CONCLUSION. The combination of ifosfamide, paclitaxel, and cisplatin is a w ell-tolerated outpatient regimen with significant activity in the treatment of newly diagnosed FIGO Stage III or IV epithelial ovarian carcinoma. Furt her evaluation is justified to clearly define the role of ifosfamide as an additional agent to the current platinum and paclitaxel regimens. (C) 2001 American Cancer Society.