Comparison of Tissue and Blood Concentrations of Oxaliplatin Administrated by Different Modalities of Intraperitoneal Chemotherapy
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Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new technology for delivering intraperitoneal chemotherapy. It is generally assumed that with PIPAC, the ratio of peritoneal to systemic drug concentration is superior to liquid hyperthermic intraperitoneal chemotherapy (HIPEC). To date, no direct comparative data are available supporting such an assumption.
Materials and Methods
Twelve 65-day-old pigs were randomly separated into three groups of four pigs each, all of which received intraperitoneal chemotherapy using the following administration methods: PIPAC with oxaliplatin 92 mg in 150 ml dextrose 5% (Group 1); PIPAC with electrostatic aerosol precipitation (ePIPAC; Group 2); or laparoscopic HIPEC (L-HIPEC) with oxaliplatin 400 mg in 4 L dextrose 5% at 42 °C (Group 3). Serial blood and peritoneal tissue concentrations of oxaliplatin were determined by spectrometry.
In all three groups, the maximum concentration of oxaliplatin in blood was detected 50–60 min after onset of the chemotherapy experiments, with no significant differences among the three groups (p = 0.7994). Blood oxaliplatin concentrations (0–30 min) were significantly higher in the L-HIPEC group compared with the ePIPAC group (p < 0.05). No difference was found for the overall systemic oxaliplatin absorption (area under the curve). Overall concentrations in the peritoneum were not different among the three groups (p = 0.4725), but were significantly higher in the visceral peritoneum in the PIPAC group (p = 0.0242).
Blood and tissue concentrations were comparable between all groups; however, depending on the intraperitoneal area examined and the time points of drug delivery, the concentrations differed significantly between the three groups.
The authors are thankful to the staff of the CIRS Department at INRA Centre, Val de Loire, France, for their important support in performing the animal experiments. The authors are also deeply thankful to Julien Sobilo at CIPA-TAAM, CNRS Orleans, for data processing, and Katarzyna Gaj for her important secretarial assistance.
UG-P: Study design, animal experiments, data acquisition, data interpretation, manuscript drafting, and critical revision for important intellectual content of the manuscript. PB, ALP: Study design, study protocol, and critical revision for important intellectual content of the manuscript. SR, ALP, SL: Critical revision for important intellectual content of the manuscript. TAF: Animal experiments and data acquisition. NT: Data analysis and interpretation. CD: Critical revision for important intellectual content of the manuscript. ES: Critical revision for important intellectual content of the manuscript. MO: Study design, study protocol, animal experiments, data acquisition, data interpretation, manuscript drafting, and critical revision for important intellectual content of the manuscript.
This study was funded by institutional funds.
Urs Giger-Pabst, Petru Bucur, Sébastien Roger, Thomas Albert Falkenstein, Nicolas Tabchouri, Alain Le Pape, Stéphanie Lerondel, Cédric Demtröder, Ephrem Salamé, and Mehdi Ouaissi have no conflicts of interest to declare.
Availability of Data and Materials
The dataset of the current study is available from the corresponding author upon reasonable request.
The study protocol was approved by the local Animal Ethics Committee, Val de Loire, France.
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