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Safety, pharmacokinetics and tissue penetration of PIPAC paclitaxel in a swine model

Peritoneal carcinomatosis is difficult to treat. Pressurized Intra-Peritoneal Aerosolised Chemotherapy (PIPAC) is a novel method of delivering chemotherapy to the peritoneal cavity, aiming for homogenous and deeper drug distribution. To date, limited chemotherapeutics have been used with promising r...

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Published in:European journal of surgical oncology 2021-05, Vol.47 (5), p.1124-1131
Main Authors: Tan, Hon Lyn, Kim, Guowei, Charles, Christopher John, Li, Renee R., Jang, Clarisse JM, Shabbir, Asim, Chue, Koy Min, Tai, Chia Hui, Sundar, Raghav, Goh, Boon Cher, Bonney, Glenn Kunnath, Looi, Wen Donq, Cheow, Esther SH, So, Jimmy BY, Wang, Lingzhi, Yong, Wei Peng
Format: Article
Language:English
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Summary:Peritoneal carcinomatosis is difficult to treat. Pressurized Intra-Peritoneal Aerosolised Chemotherapy (PIPAC) is a novel method of delivering chemotherapy to the peritoneal cavity, aiming for homogenous and deeper drug distribution. To date, limited chemotherapeutics have been used with promising results. Here, we evaluate the pharmacokinetics, peritoneal tissue drug concentration, penetration, and short-term safety of PIPAC using solvent-based paclitaxel in swine to guide clinical trials. PIPAC solvent-based paclitaxel was administered at 60, 30, and 15mg/m2 for 3 cohorts. Each PIPAC procedure was followed by intravenous (IV) administration of the same dose of solvent-based paclitaxel on Day 7, serving as control for pharmacokinetic comparison in the same pig. Safety and toxicity were evaluated by clinical assessment, blood counts and biochemistry. Blood samples were taken for pharmacokinetic analysis. Peritoneal biopsies were taken to measure tissue paclitaxel concentrations and distribution. 12 Yorkshire x Landrace pigs underwent trial procedures. With PIPAC, there was linear pharmacokinetics and lower systemic exposure to paclitaxel compared to IV administration. MALDI-MSI demonstrated concentration of paclitaxel at the peritoneal surface, with estimated 2 mm penetration. PIPAC paclitaxel had favorable toxicity profile. The most significant adverse event was neutropenia which was dose dependent, with absolute neutrophil count
ISSN:0748-7983
1532-2157
DOI:10.1016/j.ejso.2020.06.031