Abstract
Intraperitoneal chemotherapy has demonstrated significant pharmacologic and clinical advantage over traditional intravenous administration for cancers that are restricted to the peritoneal cavity. The combination of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) has become the standard technique used to fight ovarian and gastrointestinal cancers in many centers. However, challenges remain for HIPEC to contact the entire peritoneal surface, penetrate the tumor tissue, and transport to the lymphatics and other metastatic sites. New innovations in delivery technique, such as heated aerosol, and in delivery molecules, such as microparticles, nanoparticles, nanogels, and tumor-penetrating peptides are being tested in animal models and will likely soon be in human trials. Improvements in overall care, such as the recent clinical trial of an oral agent for maintenance therapy in ovarian carcinoma, will continue in this field for the next 20 years.
Highlights
Despite advances over the past 20 years in treatment options for metastatic ovarian or gastrointestinal cancers, survival is relatively poor
The chief strategy that is employed at present is a combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) [1, 6]
The heated solution is infused into the peritoneal cavity immediately after cytoreductive surgery and circulated or allowed to dwell 60–120 min. This is followed by early post-operative intraperitoneal chemotherapy (EPIC) is begun in the first post-operative day and the solution dwells for 23 h, drained for 1 hour and re-administered; the duration of therapy is typically 1 week [17]
Summary
Despite advances over the past 20 years in treatment options for metastatic ovarian or gastrointestinal cancers, survival is relatively poor. Au et al [18] has developed a sophisticated multiscale tumor, spatiokinetic model for intraperitoneal therapy, which assumes contact of the treating solution with the tumor surface This effort models paclitaxel, both free and drug bound to soluble proteins, the transfer from the cavity via lymphatic drainage, transperitoneal transport, and subperitoneal tumors and tissue, as well as the disposition in the systemic compartment with final elimination. A subsequent sensitivity analysis demonstrated that parameters such as tumor interstitial diffusivity, vessel surface area per unit tissue volume, and maximum cellular binding capacity were the most important to model output This model predicts penetration of the agent given that the agent is in contact with the tumor for a specified amount of time. Others have made efforts to model or measure the penetration of macromolecules into tumors [19,20,21,22]
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