Intraperitoneal chemotherapy for peritoneal metastases: an expert opinion.

Introduction : Peritoneal metastasis (PM) is a common manifestation of ovarian and gastro-intestinal cancer. Compared to parenchymal metastasis, PM is less amenable to systemic chemotherapy, and may cause debilitating symptoms. The rationale for intraperitoneal (IP) drug delivery is based on the pharmacokinetic advantage resulting from the peritoneal-plasma barrier, and on the potential to adequately treat small, poorly vascularized PM. Despite a history of more than three decades, many aspects of IP drug delivery remain poorly studied. Areas covered : We outline the anatomy and physiology of the peritoneal cavity, including the pharmacokinetics of IP drug delivery. We discuss transport mechanisms governing tissue penetration of IP chemotherapy, including diffusion and convection, and how these are affected by the biomechanical properties of the tumor stroma. We provide an overview of the current clinical evidence on IP chemotherapy, including hyperthermic IP chemoperfusion (HIPEC), in ovarian, colorectal, and gastric cancer. We discuss the current limitations of IP drug delivery and propose several potential areas of progress including IP aerosol delivery, the use of IP nanomedicine, and developments in the field of novel prolonged release formulations and biomaterials. Expert opinion : The potential of IP drug delivery is currently hampered by the lack of industrial interest, resulting in off-label use of drugs developed for systemic therapy. The clinical efficacy of IP chemotherapy for PM is highly variable and depends on cancer type, disease extent, and mode of drug delivery. Results from ongoing randomized trials will allow to better delineate the potential of IP chemotherapy. Novel and promising approaches include aerosol IP delivery, the use of prolonged delivery platforms such as gels or biomaterials, and the use of nanomedicine.