PHASE-II TRIAL FOR INTRAPERITONEAL CISPLATIN PLUS INTRAVENOUS-SODIUM THIOSULFATE IN ADVANCED OVARIAN-CARCINOMA PATIENTS WITH MINIMAL RESIDUAL DISEASE AFTER CISPLATIN-BASED CHEMOTHERAPY - A PHASE-II STUDY OF THE EORTC GYNECOLOGICAL CANCER COOPERATIVE GROUP

On the basis of its efficacy against ovarian carcinoma and its safe pe ritoneal administration, cisplatin administered by the intraperitoneal route was studied in a phase II multicentric trial. 34 patients with good performance status and residual disease less than 1 cm were treat ed with a 90 mg/m(2) dose (60 mg/m(2) at first cycle), administered in the abdominal cavity every 3 weeks for at least four cycles. In case of haematological or renal toxicity, intravenous sodium thiosulphate w as perfused simultaneously with intraperitoneal cisplatin with protect ive intent. 25 patients were evaluable for response: 3 patients had pa thological complete response and 1 patient had a microscopic disease ( 16% response rate in evaluable patients). Systemic toxicity was mild, and sodium thiosulphate clearly protected against leucopenia (6 patien ts) and renal toxicity (8 patients). Local side-effects were evaluable in 34 patients with 2 cases of infectious peritonitis, 1 of wound inf ection and 2 of haemorrhage. Of the 147 evaluable chemotherapy cycles, nine resulted in partial and one in total inflow obstruction, for whi ch 4 patients needed surgical procedures for catheter-related complica tions, and 1 patient died of acute abdominal complications after such a procedure. We conclude that 90 mg/m(2) intraperitoneal cisplatin has activity in pretreated patients with minimal residual disease, and th at thiosulphate protects against haematological and renal toxicities. Only a randomised study can demonstrate a true benefit, which will hav e to be balanced with the toxicity of intraperitoneal drug administrat ion.