Concentrations of cisplatin and doxorubicin in ascites and peritoneal tumor nodules before and after pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with peritoneal metastasis

Tempfer, Clemens B.; Hilal, Ziad; Doğan, Aşkın; Petersen, Miriam; Rezniczek, Günther A.

doi:10.1016/j.ejso.2018.04.020

Cited by 23 publications

(12 citation statements)

References 18 publications

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“…During PIPAC, chemotherapy is delivered as an aerosol, generated by a nebulizer (Capnopen®) connected to a high-pressure injector. This novel approach may overcome two major limitations of conventional liquid based IP chemotherapy: incomplete coverage the peritoneal surfaces and poor tissue drug penetration [22, 23]. The increased intra-abdominal pressure during PIPAC by means of the capnoperitoneum may overcome the high interstitial fluid pressure in tumor tissue, and therefore improve tissue penetration [9].…”

Section: Discussionmentioning

confidence: 99%

Establishment of a rat ovarian peritoneal metastasis model to study pressurized intraperitoneal aerosol chemotherapy (PIPAC)

et al. 2019

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Background pressurized intraperitoneal aerosol chemotherapy (PIPAC), with or without electrostatic precipitation (ePIPAC), was recently introduced in the treatment of peritoneal metastases (PM) from ovarian cancer (OC). Preliminary clinical data are promising, but several methodological issues as well the anticancer efficacy of PIPAC remain unaddressed. Here, we propose a rat ePIPAC model that allows to study these issues in a clinically relevant, reproducible, and high throughput model. Methods laparoscopy and PIPAC were established in healthy Wistar rats. Aerosol properties were measured using laser diffraction spectrometry based granulometric analyses. Electrostatic precipitation was accomplished using a commercially available generator (Ultravision™). A xenograft model of ovarian PM was created in athymic rats using intraperitoneal (IP) injection of SKOV-3 luciferase positive cells. Tumor growth was monitored weekly by in vivo bioluminescence imaging. Results PIPAC and electrostatic precipitation were well tolerated using a capnoperitoneum of 8 mmHg. All rats survived the (e)PIPAC procedure and no gas or aerosol leakage was observed over the entire procedure. With an injection pressure of 20 bar, granulometry showed a mean droplet diameter (D(v,0.5)) of 47 μm with a flow rate of 0.5 mL/s, and a significantly lower diameter (30 μm) when a flow rate of 0.8 mL/s was used. Experiments using IP injection of SKOV-3 luciferase positive cells showed that after IP injection of 20 × 10 6 cells, miliary PM was observed in all animals . PIPAC was feasible and well supported in these tumor bearing animals. Conclusions we propose a reproducible and efficient rodent model to study PIPAC and ePIPAC in OC xenografts with widespread PM. This model allows to characterize and optimize pharmacokinetic and biophysical parameters, and to evaluate the anti-cancer efficacy of (e)PIPAC treatment.

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Section: Discussionmentioning

confidence: 99%

Establishment of a rat ovarian peritoneal metastasis model to study pressurized intraperitoneal aerosol chemotherapy (PIPAC)

et al. 2019

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“…Based on the locoregional administration of pressurized aerosol drugs, it maximizes exposure of peritoneal tumor implants to chemotherapy agents, with favorable pharmacokinetics and biodistribution, as demonstrated in several pre-clinical studies. 14 , 15 …”

Section: Introductionmentioning

confidence: 99%

Pressurized intraperitoneal aerosol chemotherapy with cisplatin and doxorubicin or oxaliplatin for peritoneal metastasis from pancreatic adenocarcinoma and cholangiocarcinoma

Giorgio

Sgarbură²,

Rotolo

et al. 2020

Ther Adv Med Oncol

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Background: Systemic chemotherapy for pancreatic adenocarcinoma (PDAC) and cholangiocarcinoma (CC) with peritoneal metastases (PM) is affected by several pharmacological shortcomings and low clinical efficacy. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is expected to maximize exposure of peritoneal nodules to antiblastic agents. This study aims to evaluate safety and efficacy of PIPAC for PM of PDAC and CC origin. Methods: This is a retrospective analysis of consecutive PDAC and CC cases with PM treated with PIPAC at two European referral centers for peritoneal disease. We prospectively recorded from August 2016 to May 2019 demographic, clinical, surgical, and oncological data. We performed a feasibility and safety assessment and an efficacy analysis based on clinical and pathological regression. Results: Twenty patients with PM from PDAC (14) and CC (six) underwent 45 PIPAC administrations. Cisplatin–doxorubicin or oxaliplatin were administered to eight and 12 patients, respectively. We experienced one intraoperative complication (small bowel perforation) and 18 grade 1–2 postoperative adverse events according to Common Terminology Criteria for Adverse Events version 4.0. A pathological regression was recorded in 50% of patients (62% in the cisplatin–doxorubicin cohort and 42% in the oxaliplatin one). Median survival from the first PIPAC was 9.7 and 10.9 months for PDAC and CC, respectively. Conclusion: PIPAC resulted feasible and safe without relevant toxicity issues, with both cisplatin–doxorubicin and oxaliplatin. The pathological response observed supports the evidence of antitumoral activity. Despite the study limitations, these outcomes are encouraging, recommending PIPAC in prospective, controlled trials in the palliative setting or the first line chemotherapy for PM from PDAC and CC.

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“…Pressurized intra-peritoneal aerosol chemotherapy (PIPAC) has recently been introduced as a palliative option for treating PM and has shown encouraging clinical results [ 1 ]. Superior pharmacological properties of PIPAC have been demonstrated in preclinical models [ 2 , 3 ] and clinical settings [ 4 – 6 ]. The current technology for generating PIPAC aerosols is a, conical single-fluid nozzle driven by an industry-standard high-pressure angioinjector [ 7 ].…”

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confidence: 99%

Comparison between microcatheter and nebulizer for generating Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC)

et al. 2020

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Background This study compares an endoscopic microcatheter and a nebulizer for delivering Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC). Methods This is an in vitro and ex vivo study in an established model (inverted bovine urinary bladder). Four parameters were compared to determine the performance of a micro-perforated endoscopic spray catheter vs. state-of-the art, nozzle technology: (1) surface coverage and pattern with methylene blue on blotting paper at three different distances; (2) median aerodynamic diameter (MAD) of aerosol droplets with three different solutions (H2O, Glc 5% and silicon oil); (3) depth of tissue penetration of doxorubicin (DOX) and (4) tissue concentration of cisplatin (CIS) and DOX using standard clinical solutions. Results The spray area covered by the microcatheter was larger (p < 0.001) but its pattern was inhomogenous than with the nozzle technology. We found that aerosol droplets were larger in the test group than in the control group for all three solutions tested. Median tissue penetration of DOX was lower (980 µm) with the microcatheter than with the nebulizer (1235 µm) and distribution was more heterogeneous ( = 0.003) with the microcatheter. The median tissue concentration of DOX and CIS was lower and concentration of DOX was more heterogeneous with the microcatheter (p = 0.002). Conclusions This investigation has revealed that microcatheter technology generates larger aerosol droplet size, less drug tissue penetration and lower drug tissue concentration than the current nozzle technology. In the absence of clinical studies, use of microcatheters for delivering PIPAC can not be recommended at this stage.

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Concentrations of cisplatin and doxorubicin in ascites and peritoneal tumor nodules before and after pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with peritoneal metastasis

Cited by 23 publications

References 18 publications

Establishment of a rat ovarian peritoneal metastasis model to study pressurized intraperitoneal aerosol chemotherapy (PIPAC)

Establishment of a rat ovarian peritoneal metastasis model to study pressurized intraperitoneal aerosol chemotherapy (PIPAC)

Pressurized intraperitoneal aerosol chemotherapy with cisplatin and doxorubicin or oxaliplatin for peritoneal metastasis from pancreatic adenocarcinoma and cholangiocarcinoma

Comparison between microcatheter and nebulizer for generating Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC)

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