Evidence for efficacy

In a subset of patients, the peritoneal cavity may represent the only site of malignancy. Left untreated, prognosis is poor and symptoms such as bowel obstruction and ascites can lead to significant morbidity. Historically the only treatment offered for carcinomatosis was systemic chemotherapy which is known to have limited effect. More recently, attempts at aggressive surgical debulking followed by the use of intraoperative heated intraperitoneal chemotherapy (HIPEC) have been used to improve the outcome for this group of patients.

HIPEC delivers chemotherapy directly to the malignant cell in the peritoneal cavity at concentrations much higher than would be tolerated by systemic chemotherapy, due to limited diffusion into the systemic circulation. Hyperthermia causes tumor cell membrane disruption and programmed cell death and is thereby directly toxic to tumors. Hyperthermia also alters blood flow to tumor tissue (compared to normal tissue) and has been shown to potentiate the cytotoxic effect of chemotherapy. Temperatures between 41 and 43 degrees Celsius are well-tolerated by normal tissue, but are cytotoxic to malignant cells.  The most commonly used agents in HIPEC are Mitomycin C and Oxaliplatin. 

The best support for the role of HIPEC therapy in treating patients with peritoneal carcinomatosis comes from a randomized trial published in 2003 from the Netherlands (References:1) In this trial 105 patients with peritoneal carcinomatosis from colorectal cancer were randomized to either treatment with systemic chemotherapy or surgical debulking, HIPEC and then systemic chemotherapy. The results showed a doubling of median survival in the group treated with surgery and HIPEC (22.2 months) compared to systemic therapy alone (12.6 months).

In addition to this trial, a number of phase II trials in carcinomatosis from colorectal cancer as well as other tissue types have shown improved survival in patients undergoing surgical debulking and HIPEC compared to historical data of systemic therapy only. A recently published consensus statement reports that HIPEC should be considered the new standard-of-care for patients with colon cancer metastases in the abdomen (References:3).