Abstract
Simple SummaryPatients with cancer of the digestive system or ovarian cancer are at risk of developing peritoneal metastases (PM). In some patients with PM, surgery followed by intraperitoneal (IP) chemotherapy has emerged as a valid treatment option. The addition of hyperthermia is thought to further enhance the efficacy of IP chemotherapy. However, the results of recent clinical trials in large bowel cancer have put into question the use of hyperthermic intraperitoneal chemotherapy (HIPEC). Here, we review the rationale and current results of HIPEC for PM and propose a roadmap to further progress.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.
Highlights
Peritoneal metastases (PM) are a common manifestation of abdominal malignancies, most frequently occurring in patients with upper gastrointestinal, colorectal, and ovarian cancer [1,2,3]
The aims of this review are 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 heated intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal malignancies
The majority of epithelial ovarian cancer (EOC) patients presents with peritoneal metastases and around 75% will relapse in the peritoneal cavity after successful first line treatment
Summary
Peritoneal metastases (PM) are a common manifestation of abdominal malignancies, most frequently occurring in patients with upper gastrointestinal, colorectal, and ovarian cancer [1,2,3]. As anticancer drugs are usually administered systemically exposing healthy tissue, their therapeutic index is limited Some of these shortcomings can be addressed by local or locoregional delivery of chemotherapy. The interest in intraperitoneal drug delivery (IPDD) was rekindled with the publications of Dedrick in the 1970s He proposed a theoretical framework for IPDD based on the pharmacokinetic (PK) advantage that results from the fact that systemic drug clearance is much faster compared to peritoneal clearance. The aims of this review are 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. Pressure driven (convective) drug transport depends on the hydraulic conductivity of the tissue, which is affected by the viscosity of the interstitial fluid and by mechanical stiffness of the tumor stroma [21]
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