Modelling drug transport during intraperitoneal chemotherapy

Steuperaert, Margo; Debbaut, Charlotte; Segers, Patrick; Ceelen, Wim

doi:10.1515/pp-2017-0004

Cited by 22 publications

(20 citation statements)

References 62 publications

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“…This underlines the need for optimal cytoreductive surgery to precede intraperitoneal chemotherapy. Drug penetration into solid tumours is a complex mass transport process that involves multiple parameters not only related to the used cytotoxic agent, but also to the tumour tissue properties and even the therapeutic setup [17]. Besides the drug characteristics and pharmacokinetic variables, their penetration depth is determined by factors such as tumour nodule size, cell density, extracellular matrix, vascularity, interstitial fluid pressure and binding [18,19].…”

Section: Pharmacodynamic Aspects Of Intraperitoneal Chemotherapymentioning

confidence: 99%

“…Besides the drug characteristics and pharmacokinetic variables, their penetration depth is determined by factors such as tumour nodule size, cell density, extracellular matrix, vascularity, interstitial fluid pressure and binding [18,19]. Various mathematical models have been proposed which can provide unique insights into the different transport barriers that occur during intraperitoneal chemotherapy [17,[19][20][21].…”

Section: Pharmacodynamic Aspects Of Intraperitoneal Chemotherapymentioning

confidence: 99%

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Pharmacological principles of intraperitoneal and bidirectional chemotherapy

Bree

Michelakis

Stamatiou

et al. 2017

Pleura and Peritoneum

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Intraperitoneal chemotherapy is associated with a significant pharmacokinetic and pharmacodynamic benefit and can, alone or in combination with systemic chemotherapy (bidirectional chemotherapy), be used for treating primary and secondary peritoneal surface malignancies. Due to the peritoneal-plasma barrier, high intraperitoneal drug concentration can be achieved by intraperitoneal chemotherapy, whereas systemic concentration remains low. Bidirectional chemotherapy may provide in addition adequate drug concentrations from the side of the subperitoneal space to the peritoneal tumour nodules. Major pharmacological problems of intraperitoneal chemotherapy are limited tissue penetration and poor homogeneity of drug distribution to the entire seroperitoneal surface. Significant pharmacological determinants of intraperitoneal chemotherapy are choice of drug, drug dosage, solution volume, carrier solution, intra-abdominal pressure, temperature, duration, mode of administration, extent of peritonectomy and interindividual variability. Drugs most commonly applied for intraperitoneal chemotherapy include mitomycin C, cisplatin, carboplatin, oxaliplatin, irinotecan, 5-fluoruracil, gemcitabine, paclitaxel, docetaxel, doxorubicin, premetrexed and melphalan. The drugs and their doses that are used vary widely among centres. While the adequate drug choice for intraperitoneal and bidirectional chemotherapy is essential, randomized clinical trials to determine the most optimal drug or drug combination are lacking, and only eight retrospective comparative clinical studies are available. Further clinical pharmacological studies are required to determine the most effective drug regimen for intraperitoneal and bidirectional chemotherapy in various indications. In the future, reliable drug sensitivity testing and genetic profiling of peritoneal metastases will be needed for enabling patient-specific therapy.

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Section: Pharmacodynamic Aspects Of Intraperitoneal Chemotherapymentioning

confidence: 99%

Section: Pharmacodynamic Aspects Of Intraperitoneal Chemotherapymentioning

confidence: 99%

Pharmacological principles of intraperitoneal and bidirectional chemotherapy

Bree

Michelakis

Stamatiou

et al. 2017

Pleura and Peritoneum

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“…In silico simulation, i.e., using computational fluid dynamics models of drug delivery and interstitial fluid pressure, offer the possibility to model the influence of physical parameters on tissue drug delivery. By providing insights into the effect of modifying these parameters on peritoneal drug uptake, in silico modelling limits the need for in vivo experiments [108]. However, such simulations do not completely alleviate the need for confirmatory experimental measures.…”

Section: In Silico Modellingmentioning

confidence: 99%

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

Nadiradze

Horvath

Sautkin

et al. 2019

Cancers

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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.

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“…Since the penetration distance of drug into tissue is short, it reaches tissues mainly through circulation over this distance rather than direct penetration. The drug distribution during HIPEC is a complex process and there are several parameters to affect transport of the drug intraperitoneally [11]. However, heat is the key factor.…”

Section: Introductionmentioning

confidence: 99%

Effect of hyperthermia on improving neutrophil restoration after intraperitoneal chemotherapy

Huang

Hsu

et al. 2019

International Journal of Hyperthermia

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Purpose: Intraperitoneal (IP) chemotherapy has several benefits but also can have severe hematologic side effects. We compared the effects of hyperthermic intraperitoneal chemotherapy (HIPEC) and conventional IP chemotherapy on bone marrow suppression and evaluated whether HIPEC increased neutrophil recovery. Methods: HIPEC or IP chemotherapy was administered to ovarian cancer-bearing mice. Bone marrow progenitor cell colony-forming unit (CFU) count, serum cytokine levels, and peripheral leukocyte count after HIPEC and IP chemotherapy were compared. Results: Peripheral neutrophil count, cytokine (G-CSF and CXCL1/KC) levels, and bone marrow progenitor cell CFU count were significantly higher after HIPEC than after IP chemotherapy. Conclusions: Hyperthermia increased the serum neutrophil-recruiting cytokine levels and reduced the magnitude of chemotherapy-induced neutropenia. Thus, HIPEC improved neutrophil and bone marrow recovery compared with conventional IP chemotherapy.

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Modelling drug transport during intraperitoneal chemotherapy

Cited by 22 publications

References 62 publications

Pharmacological principles of intraperitoneal and bidirectional chemotherapy

Pharmacological principles of intraperitoneal and bidirectional chemotherapy

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

Effect of hyperthermia on improving neutrophil restoration after intraperitoneal chemotherapy

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