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In patients with tumors confined to the peritoneal cavity, there is established pharmacokinetic and tumor biology-related evidence that intraperitoneal drug administration is advantageous. Three large randomized trials in patients with stage III ovarian cancer who underwent optimal cytoreduction have demonstrated a significant survival benefit when intraperitoneal chemotherapy was added to systemic therapy. Although intraperitoneal therapy is associated with locoregional toxic effects, recent trials suggest that with some modification of the local delivery methods this approach is safe in 80% of patients in an ambulatory setting. Surgical cytoreduction immediately followed by intraoperative hyperthermic intraperitoneal chemoperfusion (HIPEC) ensures intraperitoneal delivery of the drug to all peritoneal surfaces and the advantages of combined hyperthermia to be exploited. An increasing number of centers are initiating this multimodality therapy in ovarian cancer and colorectal cancer. Clearly, intraperitoneal drug delivery is an important adjunct to surgery and systemic chemotherapy in selected patients. The optimal drug, dose and schedule for intraperitoneal delivery, the exact role of added HIPEC compared with cytoreduction alone, and the potential role of HIPEC in ovarian cancer and peritoneal mesothelioma are still undefined. Several randomized controlled trials addressing these uncertainties have been initiated.

Approximately 1 in 30 patients suffering from colorectal cancer (CRC) will develop peritoneal carcinomatosis (PC) in the absence of systemic spread. The mechanisms giving rise to PC in CRC are incompletely understood, but involve a complex stepwise interaction between the malignant cell and mesothelial layer. Systemic palliative chemotherapy is usually offered, but of limited activity in PC. Cytoreductive surgery followed by intraperitoneal hyperthermic chemoperfusion (HIPEC) has been described recently in management of isolated PC originating from CRC, based on a sound biological rationale of synergism and a pharmacokinetical advantage. Several retrospective series, one prospective randomized trial, and a meta analysis have clearly shown a survival benefit for patients treated with cytoreduction + HIPEC provided a complete (R0) resection is performed. Toxicity of the procedure is considerable, and mainly depends on the extent of surgery. Future trials are needed to provide more solid evidence in favor of surgery in PC originating from CRC in the era of modern chemotherapy and to better define the role of HIPEC as an adjunct to surgery.