CONTINUOUS-INFUSION OF IFOSFAMIDE AND CISPLATIN AS FIRST-LINE THERAPYOF PATIENTS WITH SUBOPTIMALLY DEBULKED STAGE III-IV EPITHELIAL OVARIAN-CANCER

Ifosfamide can be effective in patients with chemo-resistant ovarian c ancer. It has also been shown to reduce intracellular glutathione (GSH ) levels. GSH reduction may play a potential role in prevention of dru g resistance and potentiation of cisplatin cytotoxicity. We conducted a prospective study of chemotherapy-naive patients with bulky, stage I II and IV epithelial ovarian cancer. Patients received 1 gm/m(2) ifosf amide per day as a 24-hour continuous infusion over six consecutive da ys followed by 100 mg/m(2) cisplatin as a 24-hour continuous infusion overlapping the sixth day infusion of ifosfamide. Patients were planne d to receive six cycles, three weeks apart. Twenty-one patients were a ccrued, all could be evaluated. The mean age was 48.7 +/- 10.2 years. The majority (62%) had grade II (489/0) serous cystadenocarcinoma. One -third of the patients had stage IV disease. Three patients with exten sive 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 (g reater than or equal to 2 cm) disease was left behind. Two-thirds of t he patients underwent complete remission of their disease with an over all response rate of 81%. Median disease-free and overall survivals we re 15 and 28 months, respectively. Three patients are still alive afte r five years, two of them are disease-free. Toxicity was primarily mye losuppression and easily manageable. Ifosfamide and cisplatin combinat ion chemotherapy results in a high response rate and survival in patie nts with suboptimally debulked, stage III and IV epithelial ovarian ca ncer. These results require confirmation in a larger prospective trial .