Designing HIPEC regimens for colon cancer: Is the available evidence being appropriately considered?

Abstract The treatment of peritoneal metastases (PM) from colorectal cancer (CRC) has been revolutionized by the availability of cytoreductive surgery (CRS), traditionally coupled with Hyperthermic Intraperitoneal Peroperative Chemotherapy (HIPEC). The impact of HIPEC itself, over the effect of surgery is poorly understood and the presence of various HIPEC regimens for CRC PM complicates objective evaluation. A recent randomized controlled trial (RCT) evaluating one of the CRC HIPEC regimens (30 min of intraperitoneal (IP) oxaliplatin) showed no increase in survival compared to CRS alone. There is uncertainty regarding the current and future use of HIPEC in CRC PM. A reevaluation of existing and the publication of new preclinical work is needed, to analyze potential efficacy of alterantive HIPEC regimens. New advanced phase clinical trials should not be started without convincing preclinical and early phase data on new IP chemotherapy regimens. This review is a critical appraisal of the available preclinical and clinical data to support the design of an alternative HIPEC regimen for CRC focusing on CRC PM specific data. We find that current evidence supports several regimens that have not been tested in prospective clinical trials while the one tested in the PRODIGE-7 RCT has little supportive evidence.