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Published in: Annals of Surgical Oncology 13/2019

01-12-2019 | Cytostatic Therapy | Gastrointestinal Oncology

Comparison of Tissue and Blood Concentrations of Oxaliplatin Administrated by Different Modalities of Intraperitoneal Chemotherapy

Authors: Urs Giger-Pabst, MD, Petru Bucur, MD, PhD, Sébastien Roger, PhD, Thomas Albert Falkenstein, MD, Nicolas Tabchouri, MD, Alain Le Pape, PhD, Stéphanie Lerondel, PhD, Cédric Demtröder, MD, Ephrem Salamé, MD, PhD, Mehdi Ouaissi, MD, PhD

Published in: Annals of Surgical Oncology | Issue 13/2019

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Abstract

Background

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.

Results

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).

Conclusions

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.
Literature
1.
go back to reference Goodman MD, McPartland S, Detelich D, et al. Chemotherapy for intraperitoneal use: a review of hyperthermic intraperitoneal chemotherapy and early post-operative intraperitoneal chemotherapy. J Gastrointest Oncol. 2016;7:45–57.CrossRef Goodman MD, McPartland S, Detelich D, et al. Chemotherapy for intraperitoneal use: a review of hyperthermic intraperitoneal chemotherapy and early post-operative intraperitoneal chemotherapy. J Gastrointest Oncol. 2016;7:45–57.CrossRef
2.
go back to reference Garofalo A, Valle M, Garcia J, et al. Laparoscopic intraperitoneal hyperthermic chemotherapy for palliation of debilitating malignant ascites. Eur J Surg Oncol. 2006;32:682–5.CrossRef Garofalo A, Valle M, Garcia J, et al. Laparoscopic intraperitoneal hyperthermic chemotherapy for palliation of debilitating malignant ascites. Eur J Surg Oncol. 2006;32:682–5.CrossRef
3.
go back to reference Facchiano E, Scaringi S, Kianmanesh R, et al. Laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of malignant ascites secondary to unresectable peritoneal carcinomatosis from advanced gastric cancer. Eur J Surg Oncol. 2008;34:154–8.CrossRef Facchiano E, Scaringi S, Kianmanesh R, et al. Laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of malignant ascites secondary to unresectable peritoneal carcinomatosis from advanced gastric cancer. Eur J Surg Oncol. 2008;34:154–8.CrossRef
4.
go back to reference Valle M, Van der Speeten K, Garofalo A. Laparoscopic hyperthermic intraperitoneal peroperative chemotherapy (HIPEC) in the management of refractory malignant ascites: a multi-institutional retrospective analysis in 52 patients. J Surg Oncol. 2009;15:331–4.CrossRef Valle M, Van der Speeten K, Garofalo A. Laparoscopic hyperthermic intraperitoneal peroperative chemotherapy (HIPEC) in the management of refractory malignant ascites: a multi-institutional retrospective analysis in 52 patients. J Surg Oncol. 2009;15:331–4.CrossRef
5.
go back to reference Ba MC, Van der Speeten K, Garofalo A. Chemotherapy with laparoscope-assisted continuous circulatory hyperthermic intraperitoneal perfusion for malignant ascites. World J Gastroenterol. 2010;16:1901–7.CrossRef Ba MC, Van der Speeten K, Garofalo A. Chemotherapy with laparoscope-assisted continuous circulatory hyperthermic intraperitoneal perfusion for malignant ascites. World J Gastroenterol. 2010;16:1901–7.CrossRef
6.
go back to reference Ba MC, Long H, Zhang XL, et al. Laparoscopic hyperthermic intraperitoneal perfusion chemotherapy for patients with malignant ascites secondary to unresectable gastric cancer. J Laparoendosc Adv Surg Tech. 2016;26:32–9.CrossRef Ba MC, Long H, Zhang XL, et al. Laparoscopic hyperthermic intraperitoneal perfusion chemotherapy for patients with malignant ascites secondary to unresectable gastric cancer. J Laparoendosc Adv Surg Tech. 2016;26:32–9.CrossRef
7.
go back to reference Solaß W, Hetzel A, Nadiradze G, et al. Description of a novel approach for intraperitoneal drug delivery and the related device. Surg Endosc. 2012;26:849–1855. Solaß W, Hetzel A, Nadiradze G, et al. Description of a novel approach for intraperitoneal drug delivery and the related device. Surg Endosc. 2012;26:849–1855.
8.
go back to reference Solaß W, Kerb R, Mürdter T, et al. Intraperitoneal chemotherapy of peritoneal carcinomatosis using pressurized aerosol as an alternative to liquid solution: first evidence for efficacy. Ann Surg Oncol 2014;21:553–559.CrossRef Solaß W, Kerb R, Mürdter T, et al. Intraperitoneal chemotherapy of peritoneal carcinomatosis using pressurized aerosol as an alternative to liquid solution: first evidence for efficacy. Ann Surg Oncol 2014;21:553–559.CrossRef
9.
go back to reference Kakchekeeva T, Demtröder C, Herath NI, et al. In vivo feasibility of electrostatic precipitation as an adjunct to pressurized intraperitoneal aerosol chemotherapy (ePIPAC). Ann Surg Oncol. 2016;23:592–598.CrossRef Kakchekeeva T, Demtröder C, Herath NI, et al. In vivo feasibility of electrostatic precipitation as an adjunct to pressurized intraperitoneal aerosol chemotherapy (ePIPAC). Ann Surg Oncol. 2016;23:592–598.CrossRef
10.
go back to reference Giger-Pabst U, Tempfer CB. How to perform safe and technically optimized pressurized intraperitoneal aerosol chemotherapy (PIPAC): experience after a consecutive series of 1200 procedures. J Gastrointest Surg. 2018;22:2187–2193.CrossRef Giger-Pabst U, Tempfer CB. How to perform safe and technically optimized pressurized intraperitoneal aerosol chemotherapy (PIPAC): experience after a consecutive series of 1200 procedures. J Gastrointest Surg. 2018;22:2187–2193.CrossRef
11.
go back to reference Ferron G, Gesson-Paute A, Classe JM, et al. Feasibility of laparoscopic peritonectomy followed by intra-peritoneal chemohyperthermia: an experimental study. Gynecol Oncol. 2005;99:358–61.CrossRef Ferron G, Gesson-Paute A, Classe JM, et al. Feasibility of laparoscopic peritonectomy followed by intra-peritoneal chemohyperthermia: an experimental study. Gynecol Oncol. 2005;99:358–61.CrossRef
12.
go back to reference Jacquet P, Sugarbaker PH. Current methodologies for clinical assessment of patients with peritoneal carcinomatosis. J Exp Clin Cancer Res. 1996;15:49–58. Jacquet P, Sugarbaker PH. Current methodologies for clinical assessment of patients with peritoneal carcinomatosis. J Exp Clin Cancer Res. 1996;15:49–58.
13.
go back to reference Murono K, Kawai K, Hata K, et al. Regimens of intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal cancer. Anticancer Res. 2018;38:15–22.PubMed Murono K, Kawai K, Hata K, et al. Regimens of intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal cancer. Anticancer Res. 2018;38:15–22.PubMed
14.
go back to reference Dedrick RL, Flessner MF. Pharmacokinetic problems in peritoneal drug administration: tissue penetration and surface exposure. J Natl Cancer Inst. 1997;89:480–487.CrossRef Dedrick RL, Flessner MF. Pharmacokinetic problems in peritoneal drug administration: tissue penetration and surface exposure. J Natl Cancer Inst. 1997;89:480–487.CrossRef
15.
go back to reference Solaß W, Hetzel A, Nadiradze G, et al. Intraoperative intraperitoneal drug delivery using a nebulizer: rationale and pharmacokinetic results. Surg Endosc. 2012;26:1849–1855.CrossRef Solaß W, Hetzel A, Nadiradze G, et al. Intraoperative intraperitoneal drug delivery using a nebulizer: rationale and pharmacokinetic results. Surg Endosc. 2012;26:1849–1855.CrossRef
16.
go back to reference Solass W, Herbette A, Schwarz T, et al. Therapeutic approach of human peritoneal carcinomatosis with Dbait in combination with capnoperitoneum: proof of concept. Surg Endosc. 2012;52:847–52.CrossRef Solass W, Herbette A, Schwarz T, et al. Therapeutic approach of human peritoneal carcinomatosis with Dbait in combination with capnoperitoneum: proof of concept. Surg Endosc. 2012;52:847–52.CrossRef
17.
go back to reference Demtröder C, Solass W, Zieren J, Strumber D, Giger-Pabst U, Reymond MA. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with oxaliplatin in colorectal peritoneal metastasis. Colorectal Dis. 2016;18: 364–371.CrossRef Demtröder C, Solass W, Zieren J, Strumber D, Giger-Pabst U, Reymond MA. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with oxaliplatin in colorectal peritoneal metastasis. Colorectal Dis. 2016;18: 364–371.CrossRef
18.
go back to reference Schilling MK, Redaelli C, Krahenbuhl L, et al. Splanchnic microcirculatory changes during CO2 laparoscopy. J Am Coll Surg. 1997;184:378–382.PubMed Schilling MK, Redaelli C, Krahenbuhl L, et al. Splanchnic microcirculatory changes during CO2 laparoscopy. J Am Coll Surg. 1997;184:378–382.PubMed
19.
go back to reference Blanco A, Giger-Pabst U, Solass W, et al. Renal and hepatic toxicities after pressurized intraperitoneal aerosol chemotherapy (PIPAC). Ann Surg Oncol. 2013;20:2311–2316.CrossRef Blanco A, Giger-Pabst U, Solass W, et al. Renal and hepatic toxicities after pressurized intraperitoneal aerosol chemotherapy (PIPAC). Ann Surg Oncol. 2013;20:2311–2316.CrossRef
20.
go back to reference Göhler D, Khosrawipour V, Khosrawipour T, et al. Technical description of the microinjection pump (MIP®) and granulometric characterization of the aerosol applied for pressurized intraperitoneal aerosol chemotherapy (PIPAC). Surg Endosc. 2017;31:1778–1784.CrossRef Göhler D, Khosrawipour V, Khosrawipour T, et al. Technical description of the microinjection pump (MIP®) and granulometric characterization of the aerosol applied for pressurized intraperitoneal aerosol chemotherapy (PIPAC). Surg Endosc. 2017;31:1778–1784.CrossRef
21.
go back to reference Bellendorf A, Khosrawipour V, Khosrawipour T, et al. Scintigraphic peritoneography reveals a non-uniform 99mTc-Pertechnetat aerosol distribution pattern for pressurized intra-peritoneal aerosol chemotherapy (PIPAC) in a swine model. Surg Endosc. 2018;32:166–174.CrossRef Bellendorf A, Khosrawipour V, Khosrawipour T, et al. Scintigraphic peritoneography reveals a non-uniform 99mTc-Pertechnetat aerosol distribution pattern for pressurized intra-peritoneal aerosol chemotherapy (PIPAC) in a swine model. Surg Endosc. 2018;32:166–174.CrossRef
22.
go back to reference Göhler D, Große S, Bellendorf A, et al. Hyperthermic intracavitary nanoaerosol therapy (HINAT) as an improved approach for pressurized intraperitoneal aerosol chemotherapy (PIPAC): Technical description, experimental validation and first proof of concept. Beilstein J Nanotechnol. 2017;18:2729–2740.CrossRef Göhler D, Große S, Bellendorf A, et al. Hyperthermic intracavitary nanoaerosol therapy (HINAT) as an improved approach for pressurized intraperitoneal aerosol chemotherapy (PIPAC): Technical description, experimental validation and first proof of concept. Beilstein J Nanotechnol. 2017;18:2729–2740.CrossRef
Metadata
Title
Comparison of Tissue and Blood Concentrations of Oxaliplatin Administrated by Different Modalities of Intraperitoneal Chemotherapy
Authors
Urs Giger-Pabst, MD
Petru Bucur, MD, PhD
Sébastien Roger, PhD
Thomas Albert Falkenstein, MD
Nicolas Tabchouri, MD
Alain Le Pape, PhD
Stéphanie Lerondel, PhD
Cédric Demtröder, MD
Ephrem Salamé, MD, PhD
Mehdi Ouaissi, MD, PhD
Publication date
01-12-2019
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 13/2019
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-019-07695-z

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