Effects of High Intra-abdominal Pressure on Tissue Diffusion and Pharmacokinetics of Cisplatin During HIPEC

Detailed Summary

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising therapy for peritoneal carcinomatosis (PC) of various origins. Rather than the pharmacokinetic advantage, the uptake of chemotherapy by tumor tissue has been proposed as the best pharmacologic endpoint to assure the efficacy of HIPEC. The primary endpoints of the present phase II randomized study are to test whether the increased intra abdominal pressure (IAP) during HIPEC could: * enhance the penetration of cisplatin into the residual neoplastic and normal tissues; * elicit changes on pharmacokinetic advantage of cisplatin. Secondary endpoints are to evaluate the: * impact of high IAP on intraoperatory hemodynamic and respiratory parameters; * impact on short-term surgical outcomes (in hospital stay, morbidity, mortality). Patients affected by PC from colorectal cancer or pseudomyxoma peritonei, submitted to complete cytoreduction (residual disease \<2.5mm) would be eligible for the study. HIPEC will be performed using closed abdomen technique and cisplatin + mitomycin-C. Patients will be randomly assigned to HIPEC with low IAP (8-12 mmHg) or high IAP (18-22 mmHg). IAP will be measured using bladder catheter. High IAP will be obtained increasing the volume of perfusate. Thirty-eight patients (19 in each study groups) will be enrolled in 30 months. The randomized groups will be stratified according to tumor type.

Study Details

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Interventions