Pharmacokinetics of Cisplatin in Semi-closed Hyperthermic Peritoneal Perfusion (HPP) for Treatment of Peritoneal Carcinomatosis

Abstract

Background: This study investigates the pharmacokinetics and toxicity of cisplatin, administered by a new semi-closed hyperthermic peritoneal perfusion (HPP) technique to patients with peritoneal carcinomatosis. Materials and Methods: After surgical cytoreduction, 12 patients were given cisplatin 100 mg/m² (CDDP), introduced into the HPP circuit for 60 min at 41.7ÆC and 1200 ml/min flow rate. Perfusate and blood samples were obtained during/after perfusion, plus normal and tumor tissues samples before/after perfusion. Results: Total and ultrafiltrate (UF) CDDP had similar patterns: monophasic in peritoneum, biphasic in plasma. At the end of perfusion, total/UF platinum (Pt) concentrations in the peritoneum decreased by 63.4%-64.9%. Total/UF Pt concentrations and AUC_tot in perfusate were higher than plasmatic ones. Pt concentrations in tumor specimens were higher than in normal tissues. Conclusion: Cisplatin administered by semi-closed HPP evidenced pharmacological advantages: higher and direct drug exposure of the tumor within the peritoneal cavity, limited systemic absorption and mild toxicity.