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Dec 20, 2019;12 (1):

Overcoming Drug Resistance by Taking Advantage of Physical Principles: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC).

Giorgi Nadiradze, Philipp Horvath, Yaroslav Sautkin, Rami Archid, Frank-Jürgen Weinreich, Alfred Königsrainer, Marc A Reymond
Author Information
  1. Giorgi Nadiradze: National Center for Pleura and Peritoneum, University of Tübingen, 72076 Tübingen, Germany.
  2. Philipp Horvath: National Center for Pleura and Peritoneum, University of Tübingen, 72076 Tübingen, Germany.
  3. Yaroslav Sautkin: National Center for Pleura and Peritoneum, University of Tübingen, 72076 Tübingen, Germany.
  4. Rami Archid: National Center for Pleura and Peritoneum, University of Tübingen, 72076 Tübingen, Germany.
  5. Frank-Jürgen Weinreich: National Center for Pleura and Peritoneum, University of Tübingen, 72076 Tübingen, Germany.
  6. Alfred Königsrainer: National Center for Pleura and Peritoneum, University of Tübingen, 72076 Tübingen, Germany.
  7. Marc A Reymond: National Center for Pleura and Peritoneum, University of Tübingen, 72076 Tübingen, Germany.
PMID: 31877647 DOI: 10.3390/cancers12010034

Abstract

Theoretical considerations as well as comprehensive preclinical and clinical data suggest that optimizing physical parameters of intraperitoneal drug delivery might help to circumvent initial or acquired resistance of peritoneal metastasis (PM) to chemotherapy. Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is a novel minimally invasive drug delivery system systematically addressing the current limitations of intraperitoneal chemotherapy. The rationale behind PIPAC is: 1) optimizing homogeneity of drug distribution by applying an aerosol rather than a liquid solution; 2) applying increased intraperitoneal hydrostatic pressure to counteract elevated intratumoral interstitial fluid pressure; 3) limiting blood outflow during drug application; 4) steering environmental parameters (temperature, pH, electrostatic charge etc.) in the peritoneal cavity for best tissue target effect. In addition, PIPAC allows repeated application and objective assessment of tumor response by comparing biopsies between chemotherapy cycles. Although incompletely understood, the reasons that allow PIPAC to overcome established chemoresistance are probably linked to local dose intensification. All pharmacological data published so far show a superior therapeutic ratio (tissue concentration/dose applied) of PIPAC vs. systemic administration, of PIPAC vs. intraperitoneal liquid chemotherapy, of PIPAC vs. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) or PIPAC vs. laparoscopic HIPEC. In the initial introduction phase, PIPAC has been used in patients who were quite ill and had already failed multiple treatment regimes, but it may not be limited to that group of patients in the future. Rapid diffusion of PIPAC in clinical practice worldwide supports its potential to become a game changer in the treatment of chemoresistant isolated PM of various origins.

Keywords

aerosol chemoresistance eritoneal metastases intraperitoneal chemotherapy pressure

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Created with Highcharts 10.0.0PIPACintraperitonealchemotherapydrugvsIntraperitonealChemotherapypressureclinicaldataoptimizingparametersdeliveryinitialperitonealPMPressurizedAerosolapplyingaerosolliquidapplicationtissuechemoresistanceHIPECpatientstreatmentTheoreticalconsiderationswellcomprehensivepreclinicalsuggestphysicalmighthelpcircumventacquiredresistancemetastasisnovelminimallyinvasivesystemsystematicallyaddressingcurrentlimitationsrationalebehindis:1homogeneitydistributionrathersolution2increasedhydrostaticcounteractelevatedintratumoralinterstitialfluid3limitingbloodoutflow4steeringenvironmentaltemperaturepHelectrostaticchargeetccavitybesttargeteffectadditionallowsrepeatedobjectiveassessmenttumorresponsecomparingbiopsiescyclesAlthoughincompletelyunderstoodreasonsallowovercomeestablishedprobablylinkedlocaldoseintensificationpharmacologicalpublishedfarshowsuperiortherapeuticratioconcentration/doseappliedsystemicadministrationHyperthermiclaparoscopicintroductionphaseusedquiteillalreadyfailedmultipleregimesmaylimitedgroupfutureRapiddiffusionpracticeworldwidesupportspotentialbecomegamechangerchemoresistantisolatedvariousoriginsOvercomingDrugResistanceTakingAdvantagePhysicalPrinciples:eritonealmetastases

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