Hyperthermic Intraperitoneal Chemotherapy: A Critical Review

Abstract

With increasing awareness amongst physicians and improved radiological imaging techniques, the peritoneal cavity is increasingly recognized as an important metastatic site in various malignancies. Prognosis of these patients is usually poor as traditional treatment including surgical resection or systemic treatment is relatively ineffective. Intraperitoneal delivery of chemotherapeutic agents is thought to be an attractive alternative as this results in high tumor tissue concentrations with limited systemic exposure. The addition of hyperthermia aims to potentiate the anti-tumor effects of chemotherapy, resulting in the concept of heated intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal metastases as it was developed about 3 decades ago. With increasing experience, HIPEC has become a safe and accepted treatment offered in many centers around the world. However, standardization of the technique has been poor and results from clinical trials have been equivocal. As a result, the true value of HIPEC in the treatment of peritoneal metastases remains a matter of debate. The current review aims to provide a critical overview of the theoretical concept and preclinical and clinical study results, to outline areas of persisting uncertainty, and to propose a framework to better define the role of HIPEC in the treatment of peritoneal malignancies.

Keywords: HIPEC; drug transport; intraperitoneal; peritoneal.

Figure 1

Overview of relevant mechanisms and variables that affect tissue transport after intraperitoneal drug delivery. Drug transport is driven by convection (pressure gradient) and by diffusion (concentration gradient). The ratio of convective/diffusive transport is larger for large or nanosized compounds.

Figure 2

Platinum (Pt) penetration after HIPEC using cisplatin in a patient with peritoneal metastases from ovarian cancer. When comparing Pt penetration with histology, it is obvious that Pt penetrates the stroma much more efficiently compared to the nests of cancer cells.