Journal
EJSO
Volume 40, Issue 5, Pages 521-528Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ejso.2013.12.005
Keywords
HIPEC; MMC; 5-FU; L-OHP; Peritoneal dissemination
Funding
- Department of Surgery, Shiga University of Medical Science
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Introduction: The drugs and protocols used for hyperthermic intraperitoneal chemotherapy (HEPEC) vary among institutions. Here we show the efficacy of the 3-drug combination of mitomycin C (MMC), 5-fluorouracil (5FU), and oxaliplatin (OHP) in an in vitro simulation of HEPEC and the safety of HIPEC with these drugs during a Phase I study of patients at high risk of developing colorectal peritoneal metastasis. Methods: To simulate REPEC, we used HCT116 and WiDr cells to assess the growth inhibitory efficacy of MMC 2 mu g/mL, 5FU 200 mu g/mL, and OHP 40 mu g/mL as single drugs or their combination after an exposure time of 30 min at 37 or 42 C. In addition, nine patients underwent surgical resection of tumors and HIPEC with MMC, 5FU, and an escalating dose of OHP (90/110/130 mg/m(2)). Dose-limiting toxicity was monitored. Results: In the simulation, the 3-drug combination showed marked tumor-suppressive effects compared with those from ten times higher dose of OHP 400 mu g/mL, with significant augmentation under hyperthermic conditions. No dose-limiting toxicity occurred in the clinical study. Dose escalation was completed at the final level of OHP. Conclusions: The MMC-5FU-OHP combination showed marked growth inhibition against colorectal cancer cells under hyperthermic conditions in vitro. In the phase I study, the recommended dose of OHP was determined as 130 mg/m(2) when used with MMC and 5FU; HIPEC using MMC-5FU-OHP appears to be safe and feasible for patients at high risk of colorectal peritoneal metastasis. (C) 2013 Elsevier Ltd. All rights reserved.
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