Abstract
Background: Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is a drug delivery technique with superior pharmacological properties for treating peritoneal metastasis (PM). Adding electrostatic loading (ePIPAC) as an adjunct to aerosol and artificial hydrostatic pressure improved tissue uptake in a preclinical model. Methods: We report the first ePIPAC use in 3 patients with PM of hepatobiliary-pancreatic (HBP) origin. All 3 patients received concomitant palliative systemic chemotherapy that was discontinued in two patients. PIPAC with cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 was applied intraperitoneally at a pressure of 12 mmHg and a temperature of 37% °C for 30 min. Additionally, a voltage 7,500-9,500 V and a current≤10 µA were applied over a stainless steel brush electrode emitting a stream of electrons. Results: ePIPAC was technically feasible. No intraoperative complication was noted. The procedures were well tolerated with no adverse event CTCAE > 2. Patient 1 with PM of unknown origin (CUP with HBP phenotype) showed an objective histological and radiological response and survived 11 months. Patient 2 with ductal pancreatic cancer underwent secondary resection after ePIPAC with no residual PM; however, tumor recurred 5 months later. Patient 3 with adenocarcinoma of the gallbladder showed a radiological regression of liver infiltration and is alive after 22 months without histological evidence of PM. Conclusion: ePIPAC is technically feasible, is well tolerated and can induce tumor regression of PM in HBP cancers with and without concomitant systemic chemotherapy. These preliminary results justify prospective clinical studies with ePIPAC.
Highlights
The metastatic seeding of tumors into the peritoneal cavity remains an unmet medical need
Between 29 July 2014 and 6 October 2015, ten Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) and four electrostatic precipitation PIPAC (ePIPAC) procedures were performed in 3 patients
Solution followed by cisplatin at a dose of 7.5 mg/m2 body surface in a 150 mL NaCl 0.9% solution was applied via aerosolizer and injector
Summary
The metastatic seeding of tumors into the peritoneal cavity remains an unmet medical need. Intraperitoneal chemotherapy has been shown to have pharmacological advantages in this situation, its use remains limited [2]. Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is an innovative drug delivery system developed for treating PM [3]. PIPAC takes advantage of the physical properties of the combination of gas and pressure in order to overcome pharmacological limitations of intraperitoneal chemotherapy such as limited exposure of peritoneal surfaces and poor drug diffusion into the tumor nodes [4]. Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is a drug delivery technique with superior pharmacological properties for treating peritoneal metastasis (PM). Patient 3 with adenocarcinoma of the gallbladder showed a Keywords: aerosol, cisplatin, doxorubicin, electrostatic precipitation, gallbaldder cancer, intraperitoneal chemotherapy, pancreatic cancer, peritoneal metastasis, PIPAC, pressure
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