Silviu Cristian Voinea 1, 2 *
1 Department of Oncological Surgery, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
2 Department of Oncological Surgery, Institute of Oncology Prof. Dr. Alexandru Trestioreanu, Bucharest, Romania
* Correspondence to: Silviu Cristian Voinea, Department of Oncological Surgery, Institute of Oncology Prof. Dr. Alexandru Trestioreanu, Șoseaua Fundeni 252, 022328 Bucharest, Romania. E-mail: silviu.voinea@umfcd.ro
Abstract
Intraperitoneal chemotherapy exploits the peritoneal–plasma barrier: drugs given into the cavity reach the peritoneal surface at concentrations many times higher than in plasma, but penetrate tumor tissue only to a depth of millimeters, which confines curative-intent hyperthermic intraperitoneal chemotherapy to patients in whom cytoreductive surgery (CRS) leaves no visible or minimal residual disease. This review examines the pharmacokinetic and pharmacodynamic basis of hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC), the randomized evidence by tumor site, and their toxicity for patients and operating-room staff. In ovarian cancer, cisplatin HIPEC at interval cytoreduction (OVHIPEC-1) prolonged overall survival (OS); at surgery for platinum-sensitive first relapse the two randomized trials disagree, CHIPOR improving OS and HORSE not improving progression-free survival; carboplatin HIPEC and a Korean trial in mixed settings were negative, and guidelines are divided. In colorectal cancer, complete cytoreduction in selected patients is the standard, oxaliplatin HIPEC as tested in PRODIGE 7 added late morbidity without survival, and mitomycin C prophylaxis reduced peritoneal recurrence without a survival gain. In gastric cancer, surgery with HIPEC did not improve OS in GASTRIPEC-I or PERISCOPE II, whereas catheter-based intraperitoneal paclitaxel did in DRAGON-01. PIPAC delivers cisplatin and doxorubicin at about one tenth of systemic doses as an aerosol at 12 mmHg, with low systemic exposure, repeatable cycles and histological response assessment, but without a completed phase 3 trial. Toxicity is drug-specific: cisplatin nephrotoxicity reduced by sodium thiosulfate, mitomycin C neutropenia, oxaliplatin-related metabolic derangement and bleeding, and surface platinum contamination controlled by closed circuits and glove discipline. A framework for patient selection, regimens and program safety is proposed.