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A Phase I trial of continuous hyperthermic peritoneal perfusion with tumor necrosis factor and cisplatin in the treatment of peritoneal carcinomatosis
Author(s) -
Bartlett David L.,
Buell Joseph F.,
Libutti Steven K.,
Reed Eddie,
Lee Kang Bo,
Figg William D.,
Venzon David J.,
Alexander H. Richard
Publication year - 1998
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19980915)83:6<1251::aid-cncr27>3.0.co;2-3
Subject(s) - medicine , cisplatin , hyperthermia , urology , toxicity , area under the curve , perfusion , gastroenterology , chemotherapy , surgery , pharmacology
BACKGROUND Tumor necrosis factor (TNF), hyperthermia, and cisplatin have synergistic cytotoxicity against cancer cells in vitro. This combination may be well suited to the regional treatment of peritoneal tumor spread in patients. Continuous hyperthermic peritoneal perfusion (CHPP) is a technique that allows uniform delivery of cytotoxic agents and heat to the peritoneal surface. A Phase I trial of CHPP with TNF and cisplatin was conducted to define the maximum tolerated dose (MTD) for TNF and cisplatin under moderate hyperthermia in the treatment of peritoneal carcinomatosis. METHODS Twenty‐seven patients with peritoneal carcinomatosis underwent exploratory laparotomy and tumor 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 0 C, and a flow rate of 1.5 L/minute. Sodium thiosulfate was administered systemically during and after the perfusion as a cisplatin binding agent. RESULTS There was no operative or treatment‐related mortality in this study. CHPP resulted in a 14‐fold higher area under the concentration versus time curve (AUC) for cisplatin in the perfusate compared with plasma, 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 significant regional toxicity was identified. The median time to toleration of a regular diet was 8 days (range, 5‐20 days). CONCLUSIONS The favorable regional pharmacologic profile of the combination of cisplatin and TNF suggests that these agents administered via CHPP warrant further evaluation as prophylaxis against or treatment for peritoneal carcinomatosis. Cancer 1998;83:1251‐1261. © 1998 American Cancer Society.