Safety and Feasibility of High-Pressure/High-Dose Pressurized Intraperitoneal Aerosol Chemotherapy (HP/HD-PIPAC) for Primary and Metastatic Peritoneal Surface Malignancies

Arias, Gabriel Ramos; Sindayigaya, Rémy; Ouaïssi, Mehdi; Buggisch, Jonathan R.; Schmeding, Maximilian; Giger‐Pabst, Urs; Zieren, Jürgen

doi:10.1245/s10434-022-12698-4

Cited by 6 publications

(8 citation statements)

References 39 publications

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“…The postoperative course was characterized by four patients with minor complications (Dindo-Clavien grade I). Based on this initial experience, no clinical difference from conventional PIPAC was observed at our institution [12].…”

Section: Discussionmentioning

confidence: 99%

“…Doxorubicin, cisplatin and oxaliplatin were purchased from Hexal AG, Holzkirchen, Germany, Accord Healthcare B.V. Utrecht, The Netherlands and Medac GmbH, Wedel, Germany. Drug doses (doxorubicin 6 mg, cisplatin 30 mg and oxaliplatin 120 mg per m 2 of body surface area (BSA)) were studied according to data of phase I safety studies and clinical use [10–12]. A patient with a height of 1.90 m and a weight of 100 kg was assumed as scenario.…”

Section: Methodsmentioning

confidence: 99%

“…All patients gave their oral and written consent. All procedures were performed as previously described in detail [10, 12] and were performed by one senior surgeon (J.Z.). Oxaliplatin at a dose of 120.0 mg/m 2 body surface area (BSA) diluted in a total of 150 ml glucose 5% was administered in case of PSM of colorectal and appendiceal primary tumours.…”

Section: Methodsmentioning

confidence: 99%

“…Oxaliplatin at a dose of 120.0 mg/m 2 body surface area (BSA) diluted in a total of 150 ml glucose 5% was administered in case of PSM of colorectal and appendiceal primary tumours. For all other tumour entities, doxorubicin 6.0 mg/m 2 BSA diluted in 50 ml NaCl 0.9% followed by cisplatin 30.0 mg/m 2 BSA diluted in 150 ml NaCl 0.9% [10–12]. According to the manufacturer’s instructions for use, the MDN was operated at a liquid fluid volume flow of 1.5 ml/s with an upper pressure limit of 300 psi.…”

Section: Methodsmentioning

confidence: 99%

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Chemical/technical risk analysis of a new multi-directional nebulizer (MDN) and its clinical implementation for the safe administration of Pressurized Intraperitoneal Aerosol Chemotherapy (MDN-PIPAC)

Kockelmann,

Göhler,

Barbey

et al. 2023

Preprint

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Background/AimTo test the chemoresistance of a multi-directional nebulizer (MDN) and to establish and implement a perioperative clinical safety concept for its clinical use to deliver pressurised intraperitoneal aerosol chemotherapy (MDN-PIPAC).Study designEx-vivo nebulization of cytostatic drugs with the MDN device to assess chemoresistance/toxicological risks. Establishment of a perioperative safety concept for the clinical administration of MDN-PIPAC by ex- and in-vivo porcine simulation studies. Unicentric case series of 30 MDN-PIPACs in 21 patients with peritoneal surface malignancies (PSM). Endpoints were intraoperative adverse events and perioperative complications (Clavien-Dindo).ResultsToxicological studies/risk assessment confirm the safety of administering PIPAC with the MDN. The horizontal nozzles must protrude at least 7 mm beyond the most distal end of the trocar tip and lateral tilting should be prevented by fixation of the device in a single-arm holder. A total of 21 patients (male/female ratio: 2:1) with a mean age of 62 (range: 38-86) years underwent 30 consecutive MDN-PIPACs for peritoneal surface malignancies of different origin. ECOG 0 and 1 were seen in five and 16 patients, respectively. Thirteen, seven, and one patient underwent one, two, and three MDN-PIPACs, respectively. Two patients received only one cycle of MDN-PIPAC because they were considered candidates for cytoreductive surgery and heated intraperitoneal chemotherapy. There were no intraoperative technical/medical problems observed. Four patients suffered from postoperative grade I complications.ConclusionsCompounds leached during chemotherapy nebulization with the MDN are toxicologically safe. MDN-PIPAC administrations are safe and the postoperative course is comparable to that of the conventional PIPAC nebulizer.MINI ABSTRACTToxicological analyses confirm that doxorubicin, cisplatin, and oxaliplatin nebulized with the MDN do not release leachables that pose a toxicological risk to patients. Through technical risk analysis and PIPAC simulations, a safety concept for the administration of MDN-PIPAC was established. No technical/medical intraoperative adverse events were observed. The perioperative course was comparable to that of the conventional axial single-direction nebulizer (SDN) PIPAC.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Chemical/technical risk analysis of a new multi-directional nebulizer (MDN) and its clinical implementation for the safe administration of Pressurized Intraperitoneal Aerosol Chemotherapy (MDN-PIPAC)

Kockelmann,

Göhler,

Barbey

et al. 2023

Preprint

Self Cite

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“…To assess the chemical resistance of the nozzle material against chemotherapeutic drugs, the nozzles were at first exposed to a cytostatic solution for 12 hours and afterwards stored in the dark at room temperature for 12 days within petri dishes. The chosen cytostatic solution was prepared in accordance to the mixture of high pressure/high dose PIPAC (HP/HD-PIPAC) [10],…”

Section: Assessing Of Chemical Resistance and Chemical Compositionmentioning

confidence: 99%

Comparative Analysis of Nebulizers in Clinical use for Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC)

Goehler

Oelschlaegel²,

Ouaïssi

et al. 2023

Preprint

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Objective: Technical ex-vivo comparison of commercial nebulizer nozzles used for Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC). Methods: The performance of four different commercial nebulizer nozzles (Nebulizer; HurriChem; MCR-4 TOPOL; QuattroJet) was analysed concerning: i) technical design and principle of operation, ii) operational pressure as function of the liquid flow rate, iii) droplet size distribution via laser diffraction spectrometry, iv) spray cone angle, spray cone form as well as horizontal drug deposition by image-metric analyses and v) chemical resistance via exposing to a cytostatic solution and chemical composition by means of spark optical emission spectral analysis. Results: The Nebulizer shows quasi an identical technical design and thus also a similar performance (e.g., mass median droplet size of 29 micrometer) as the original PIPAC nozzles (MIP/ CapnoPen). All other nozzles show more or less a performance deviation to the original PIPAC nozzles. The HurriChem has a similar design and principle of operation as the Nebulizer, but provides a finer aerosol (22 micrometer). The principle of operation of MCR-4 TOPOL and QuattroJet differ significantly from that of the original PIPAC nozzle technology. The MCR-4 TOPOL offers a hollow spray cone with significantly larger droplets (50 micrometer) than the original PIPAC nozzles. The QuattroJet generates an aerosol (22 micrometer) similar to that of the HurriChem but with improved spatial drug distribution. Conclusion: The availability of new PIPAC nozzles is encouraging but can also have a negative impact if their performance and efficacy is unknown. It is recommended that PIPAC nozzles that deviate from the current standard should be subject to bioequivalence testing and implementation in accordance with the IDEAL-D framework prior to routine clinical use.

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Pressurized intraperitoneal aerosol chemotherapy (PIPAC): Why it will transform cancer surgery

Reymond,

Sautkin,

Schönfelder

et al. 2024

Formos J Surg

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Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) represents an innovative method for delivering chemotherapy directly into the abdominal cavity, offering a targeted, effective, and less toxic treatment option for patients with non-resectable peritoneal metastasis (PM). PIPAC is increasingly adopted due to its benefits over traditional therapies, including enhanced drug penetration, reduced systemic toxicity, and improved efficacy in chemoresistant PM. Performed laparoscopically, PIPAC is minimally invasive, often outpatient, and well-tolerated, preserving patients' quality of life. So far, PIPAC has been mainly used in advanced PM from ovarian, gastric, and colorectal cancers, where it can be effective even after other treatments have failed. The repeatable nature of PIPAC offers opportunities for maintenance therapy and long-term disease control. A recent meta-analysis of PIPAC studies reported a 4% non-access rate and 39% of patients completing three or more cycles, with only 4% experiencing severe toxicities. Pathological responses were observed in 68% of cases, indicating reliable efficacy. A first randomized trial showed PIPAC’s superiority in objective response rates and quality of life compared to intravenous chemotherapy for platinum-resistant ovarian cancer. Research in PIPAC is dynamic and multidisciplinary, aiming to refine the technique, minimize side effects, and expand its applicability to various cancers. Studies focus on the efficacy of aerosolized drug delivery, including nanoparticles and RNA-based therapies, which offer targeted treatment options with promising therapeutic potential. Innovations such as electrostatic precipitation PIPAC (ePIPAC) combine enhanced drug distribution with increased tissue penetration, representing significant advancements in PM treatment. Future developments will focus on optimizing aerosol characteristics, drug formulations, and personalized medicine approaches.

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Safety and Feasibility of High-Pressure/High-Dose Pressurized Intraperitoneal Aerosol Chemotherapy (HP/HD-PIPAC) for Primary and Metastatic Peritoneal Surface Malignancies

Cited by 6 publications

References 39 publications

Chemical/technical risk analysis of a new multi-directional nebulizer (MDN) and its clinical implementation for the safe administration of Pressurized Intraperitoneal Aerosol Chemotherapy (MDN-PIPAC)

Chemical/technical risk analysis of a new multi-directional nebulizer (MDN) and its clinical implementation for the safe administration of Pressurized Intraperitoneal Aerosol Chemotherapy (MDN-PIPAC)

Comparative Analysis of Nebulizers in Clinical use for Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC)

Pressurized intraperitoneal aerosol chemotherapy (PIPAC): Why it will transform cancer surgery

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