A PHASE-I TRIAL OF CONTINUOUS HYPERTHERMIC PERITONEAL PERFUSION WITH TUMOR-NECROSIS-FACTOR AND CISPLATIN IN THE TREATMENT OF PERITONEAL CARCINOMATOSIS

BACKGROUND, Tumor necrosis factor (TNF), hyperthermia, and cisplatin h ave synergistic cytotoxicity against cancer cells in vitro. This combi nation may be suited to the regional treatment of peritoneal tumor spr ead in patients. CHPP with TNF and cisplatin was conducted to define t he maximum dose (MTD) for TNF and cisplatin under moderate hyperthermi a in the of peritoneal carcinomatosis. METHODS, Twenty-seven patients with peritoneal carcinomatosis underwent exploratory laparotomy and tu mor debulking followed by a 90-minute CHPP with cisplatin (100-350 mg/ m(2)) and TNF (0-0.3 mg/L). Perfusion parameters included a perfusate volume of 3-9 L, a peritoneal temperature of 42-43 degrees C, and a fl ow rate of 1.5 L/minute. Sodium thiosulfate was administered systemica lly during and after the perfusion as a cisplatin binding agent. RESUL TS. There was no operative or treatment-related mortality in this stud y. CHPP resulted in a 14-fold higher area under the concentration vers us time curve (AUC) for cisplatin in the perfusate compared with plasm a, and a 4854-fold higher AUC for TNF. The MTD was defined as 250 mg/m (2) cisplatin plus 0.1 mg/L TNF. The dose-limiting toxicity was renal insufficiency. No other systemic toxicity was identified, and no signi ficant regional toxicity was identified. The median time to toleration of a regular diet was 8 days (range, 5-20 days). CONCLUSIONS, The fav orable regional pharmacologic profile of the combination of cisplatin and TNF suggests that these agents administered via CHPP warrant furth er evaluation as prophylaxis against or treatment for peritoneal carci nomatosis. (C) 1998 American Cancer Society.