Rationale for Heating Oxaliplatin for the Intraperitoneal Treatment of Peritoneal Carcinomatosis

Abstract

To study the effect of heat on the absorption of intraperitoneal (IP) oxaliplatin using a murine model. Because of its efficiency in the systemic treatment of colorectal cancer, oxaliplatin is currently used in hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis. However, its properties when administered by the IP route have not been well characterized by preclinical studies. Under general anesthesia, 35 Sprague-Dawley rats were submitted to 3 different doses of IP oxaliplatin (460, 920, and 1840 mg/m(2)) at 3 different perfusion temperatures (37, 40, and 43°C) during 25 minutes. At the end of perfusion, samples in different compartments (peritoneum, portal blood, and systemic blood) were harvested and the concentrations of oxaliplatin were measured by high performance liquid chromatography. As the dose of IP oxaliplatin was increased, higher concentrations were observed in every compartment. When the temperature of IP oxaliplatin was increased, it resulted in an increase of its peritoneal concentration (linear regression 0.38; 95% CI: 0.28-0.47) and in a decrease of its systemic blood (linear regression -1, 02; 95% CI: -1.45 to -0.60) and portal blood (linear regression -1.08; 95% CI: -1.70 to -0.47) concentrations. Proportionally to the dose administered, IP oxaliplatin leads to high concentration of drug in peritoneal tissues. Furthermore, heat enhances peritoneal tissue concentration of Oxaliplatin while reducing its systemic absorption. This last effect may possibly lead to decreased systemic toxicity. These observations support the use of oxaliplatin for HIPEC.