Continuous infusion of ifosfamide and cisplatin as first-line therapy of patients with suboptimally debulked stage III-IV epithelial ovarian cancer

Ifosfamide can be effective in patients with chemo-resistant ovarian cancer. It has also been shown to reduce intracellular glutathione (GSH) levels. GSH reduction may play a potential role in prevention of drug resistance and potentiation of cisplatin cytotoxicity. We conducted a prospective study of chemotherapy-naive patients with bulky, stage III and IV epithelial ovarian cancer. Patients received 1 gm/m2 ifosfamide per day as a 24-hour continuous infusion over six consecutive days followed by 100 mg/m2 cisplatin as a 24-hour continuous infusion overlapping the sixth day infusion of ifosfamide. Patients were planned to receive six cycles, three weeks apart. Twenty-one patients were accrued, all could be evaluated. The mean age was 48.7 ± 10.2 years. The majority (62%) had grade II (48%) serous cystadenocarcinoma. One-third of the patients had stage IV disease. Three patients with extensive stage-IV disease did not undergo surgery and diagnosis was based upon ascitic fluid analysis. Twelve patients had laparotomy performed, were considered inoperable, and minimal debulking was carried out. In six patients, despite aggressive attempts at debulking, suboptimal (≥2 cm) disease was left behind. Two-thirds of the patients underwent complete remission of their disease with an overall response rate of 81%. Median disease-free and overall survivals were 15 and 28 months, respectively. Three patients are still alive after five years, two of them are disease-free. Toxicity was primarily myelosuppression and easily manageable. Ifosfamide and cisplatin combination chemotherapy results in a high response rate and survival in patients with suboptimally debulked, stage III and IV epithelial ovarian cancer. These results require confirmation in a larger prospective trial.