nach oben

Erschienen in:

24.01.2019 | Research Paper

Hepatic arterial infusion of irinotecan and EmboCept^® S results in high tumor concentration of SN-38 in a rat model of colorectal liver metastases

verfasst von: Anne Kauffels, Marie Kitzmüller, Andrea Gruber, Hannah Nowack, Hanibal Bohnenberger, Melanie Spitzner, Anja Kuthning, Thilo Sprenger, Martin Czejka, Michael Ghadimi, Jens Sperling

Erschienen in: Clinical & Experimental Metastasis | Ausgabe 1/2019

Einloggen, um Zugang zu erhalten

Abstract

Intraarterial chemotherapy for colorectal liver metastases (CRLM) can be applied alone or together with embolization particles. It remains unclear whether different types of embolization particles lead to higher intratumoral drug concentration. Herein, we quantified the concentrations of CPT-11 and its active metabolite SN-38 in plasma, liver and tumor tissue after hepatic arterial infusion (HAI) of irinotecan, with or without further application of embolization particles, in a rat model of CRLM. Animals underwent either systemic application of irinotecan, or HAI with or without the embolization particles Embocept^® S and Tandem™. Four hours after treatment concentrations of CPT-11 and SN-38 were analyzed in plasma, tumor and liver samples by high-performance liquid chromatography. Additionally, DNA-damage and apoptosis were analyzed immunohistochemically. Tumor tissue concentrations of SN-38 were significantly increased after HAI with irinotecan and EmboCept^® S compared to the other groups. The number of apoptotic cells was significantly higher after both HAI with irinotecan and EmboCept^® S or Tandem™ loaded with irinotecan compared to the control group. HAI with irinotecan and EmboCept^® S resulted in an increased SN-38 tumor concentration. Both HAI with irinotecan and EmboCept^® S or Tandem™ loaded with irinotecan were highly effective with regard to apoptosis.

Nur mit Berechtigung zugänglich

Habib A, Desai K, Hickey R, Thornburg B, Lewandowski R, Salem R (2015) Transarterial approaches to primary and secondary hepatic malignancies. Nat Rev Clin Oncol 12:481–489CrossRefPubMed

Mocellin S, Pilati P, Lise M, Nitti D (2007) Meta-analysis of hepatic arterial infusion for unresectable liver metastases from colorectal cancer: the end of an era? J Clin Oncol 25:5649–5654CrossRefPubMed

McAuliffe JC, Qadan M, D’Angelica MI (2015) Hepatic resection, hepatic arterial infusion pump therapy, and genetic biomarkers in the management of hepatic metastases from colorectal cancer. J Gastrointest Oncol 6:699–708PubMedPubMedCentral

Fiorentini G, Sarti D, Aliberti C, Carandina R, Mambrini A, Guadagni S (2017) Multidisciplinary approach of colorectal cancer liver metastases. World J Clin Oncol 8:190–202CrossRefPubMedPubMedCentral

Cercek A, Boucher TM, Gluskin JS, Aguiló A, Chou JF, Connell LC et al (2016) Response rates of hepatic arterial infusion pump therapy in patients with metastatic colorectal cancer liver metastases refractory to all standard chemotherapies. J Surg Oncol 114:655–663CrossRefPubMedPubMedCentral

DʼAngelica MI, Correa-Gallego C, Paty PB, Cercek A, Gewirtz AN, Chou JF et al (2015) Phase II trial of hepatic artery infusional and systemic chemotherapy for patients with unresectable hepatic metastases from colorectal cancer: conversion to resection and long-term outcomes. Ann Surg 261:353–360CrossRefPubMed

Martin RC III, Scoggins CR, Schreeder M, Rilling WS, Laing CJ, Tatum CM et al (2015) Randomized controlled trial of irinotecan drug-eluting beads with simultaneous FOLFOX and bevacizumab for patients with unresectable colorectal liver-limited metastasis. Cancer 121:3649–3658CrossRefPubMed

Groot Koerkamp B, Sadot E, Kemeny NE, Gönen M, Leal JN, Allen PJ et al (2017) Perioperative hepatic arterial infusion pump chemotherapy is associated with longer survival after resection of colorectal liver metastases: a propensity score analysis. J Clin Oncol 35:1938–1944CrossRefPubMedPubMedCentral

Gruber-Rouh T, Marko C, Thalhammer A, Nour-Eldin NE, Langenbach M, Beeres M et al (2016) Current strategies in interventional oncology of colorectal liver metastases. Br J Radiol 26:20151060CrossRef

10.

Fujita K, Kubota Y, Ishida H, Sasaki Y (2015) Irinotecan, a key chemotherapeutic drug for metastatic colorectal cancer. World J Gastroenterol 21:12234–12248CrossRefPubMedPubMedCentral

11.

Mathijssen RH, van Alphen RJ, Verweij J, Loos WJ, Nooter K, Stoter G, Sparreboom A (2001) Clinical pharmacokinetics and metabolism of irinotecan (CPT-11). Clin Cancer Res 7:2182–2194PubMed

12.

Xie R, Mathijssen RH, Sparreboom A, Verweij J, Karlsson MO (2002) Clinical pharmacokinetics of irinotecan and its metabolites in relation with diarrhea. Clin Pharmacol Ther 72:265–275CrossRefPubMed

13.

Colucci G, Gebbia V, Paoletti G, Giuliani F, Caruso M, Gebbia N et al (2005) Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell’Italia Meridionale. J Clin Oncol 23:4866–4875CrossRefPubMed

14.

Benedict FG (1934) Die Oberflächenbestimmungen verschiedener Tiergattungen [Determination of body surface area in different animal species]. Ergeb Physiol Exp Pharmakol 36:300–346CrossRef

15.

Workman P, Aboagye EO, Balkwill F, Balmain A, Bruder G, Chaplin DJ et al (2010) Guidelines for the welfare and use of animals in cancer research. Br J Cancer 102:1555–1577CrossRefPubMedPubMedCentral

16.

Institute of Laboratory Animal Resources, National Research Council (1996) Guide for the care and use of laboratory animals, 8th edn. NIH Guide, UK

17.

Sperling J, Schäfer T, Ziemann C, Benz-Weiber A, Kollmar O, Schilling MK et al (2012) Hepatic arterial infusion of bevacizumab in combination with oxaliplatin reduces tumor growth in a rat model of colorectal liver metastases. Clin Exp Metastasis 29:91–99CrossRefPubMed

18.

Sperling J, Brandhorst D, Schäfer T, Ziemann C, Benz-Weißer A, Scheuer C et al (2013) Liver-directed chemotherapy of cetuximab and bevacizumab in combination with oxaliplatin is more effective to inhibit tumor growth of CC531 colorectal rat liver metastases than systemic chemotherapy. Clin Exp Metastasis 30:447–455CrossRefPubMed

19.

Sperling J, Schäfer T, Benz-Weißer A, Ziemann C, Scheuer C, Kollmar O et al (2013) Hepatic arterial infusion but not systemic application of cetuximab in combination with oxaliplatin significantly reduces growth of CC531 colorectal rat liver metastases. Int J Colorectal Dis 28:555–562CrossRefPubMed

20.

Eder I, Czejka M, Schueller J, Zeleny U (2000) Clinical pharmacokinetics (PHK) and metabolism of irinotecan (IRINO) during mono- and polychemotherapy with 5-Fluorouracil/Leucovorin (5FU/LV) and Docetaxel (DOCE). Eur J Pharm Sci 11:23

21.

Slatter JG, Schaaf LJ, Sams JP, Feenstra KL, Johnson MG, Bombardt PA et al (2000) Pharmacokinetics, metabolism, and excretion of irinotecan (CPT-11) following I.V. infusion of [(14)C]CPT-11 in cancer patients. Drug Metab Dispos 28:423–433PubMed

22.

Czejka M, Kiss A, Koessner C, Terkola R, Ettlinger D, Schueller J (2011) Metabolic activation of irinotecan during intra-arterial chemotherapy of metastatic colorectal cancer. Anticancer Res 31:3573–3578PubMed

23.

Basu S, Zeng M, Yin T, Gao S, Hu M (2016) Development and validation of an UPLC-MS/MS method for the quantification of irinotecan, SN-38 and SN-38 glucuronide in plasma, urine, feces, liver and kidney: application to a pharmacokinetic study of irinotecan in rats. J Chromatogr B Analyt Technol Biomed Life Sci 1015–1016:34–41CrossRefPubMedPubMedCentral

24.

Tanaka T, Nishiofuku H, Hukuoka Y, Sato T, Masada T, Takano M et al (2014) Pharmacokinetics and antitumor efficacy of chemoembolization using 40 µm irinotecan-loaded microspheres in a rabbit liver tumor model. J Vasc Interv Radiol 25:1037–1044CrossRefPubMed

25.

Gnutzmann DM, Mechel J, Schmitz A, Köhler K, Krone D, Bellemann N et al (2015) Evaluation of the plasmatic and parenchymal elution kinetics of two different irinotecan-loaded drug-eluting embolics in a pig model. J Vasc Interv Radiol 26:746–754CrossRefPubMed

26.

Baker DG, Kearney MT (2015) The need for econometric research in laboratory animal operations. Lab Anim (NY) 44:217–220CrossRef

27.

Thomas C, Nijenhuis AM, Timens W, Kuppen PJ, Daemen T, Scherphof GL (1993) Liver metastasis model of colon cancer in the rat: immunohistochemical characterization. Invasion Metastasis 13:102–112PubMed

28.

White SB, Procissi D, Chen J, Gogineni VR, Tyler P, Yang Y et al (2016) Characterization of CC-531 as a rat model of colorectal liver metastases. PLoS ONE 11:e0155334CrossRefPubMedPubMedCentral

29.

Eyol E, Boleij A, Taylor RR, Lewis AL, Berger MR (2008) Chemoembolisation of rat colorectal liver metastases with drug eluting beads loaded with irinotecan or doxorubicin. Clin Exp Metastasis 25:273–282CrossRefPubMed

30.

van Duijnhoven FH, Tollenaar RA, Terpstra OT, Kuppen PJ (2005) Locoregional therapies of liver metastases in a rat CC531 coloncarcinoma model results in increased resistance to tumour rechallenge. Clin Exp Metastasis 22:247–253CrossRefPubMed

31.

Seelig MH, Leible M, Sänger J, Berger MR (2004) Chemoembolization of rat liver metastasis with microspheres and gemcitabine followed by evaluation of tumor cell load by chemiluminescence. Oncol Rep 11:1107–1113PubMed

32.

Hutteman M, Mieog JS, van der Vorst JR, Dijkstra J, Kuppen PJ, van der Laan AM et al (2011) Intraoperative near-infrared fluorescence imaging of colorectal metastases targeting integrin α(v)β(3) expression in a syngeneic rat model. Eur J Surg Oncol 37:252–257CrossRefPubMed

33.

Krause P, Flikweert H, Monin M, Seif Amir Hosseini A, Helms G, Cantanhede G et al (2013) Increased growth of colorectal liver metastasis following partial hepatectomy. Clin Exp Metastasis 30:681–693CrossRefPubMedPubMedCentral

34.

Sperling J, Ziemann C, Gittler A, Benz-Weißer A, Menger MD, Kollmar O (2015) Tumour growth of colorectal rat liver metastases is inhibited by hepatic arterial infusion of the mTOR-inhibitor temsirolimus after portal branch ligation. Clin Exp Metastasis 32:313–321CrossRefPubMed

35.

Vollmar B, Menger MD (2009) The hepatic microcirculation: mechanistic contributions and therapeutic targets in liver injury and repair. Physiol Rev 98:1269–1339CrossRef

36.

Oda M, Yokomori H, Han JY (2003) Regulatory mechanisms of hepatic microcirculation. Clin Hemorheol Microcirc 29:167–182PubMed

37.

Koo A, Liang IY, Cheng KK (1975) The terminal hepatic microcirculation in the rat. Q J Exp Physiol Cogn Med Sci 60:261–266PubMed

38.

Gonda T, Ishida H, Yoshinaga K, Sugihara K (2000) Microvasculature of small liver metastases in rats. J Surg Res 94:43–48CrossRefPubMed

39.

Buck A, Halbritter S, Späth C, Feuchtinger A, Aichler M, Zitzelsberger H et al (2015) Distribution and quantification of irinotecan and its active metabolite SN-38 in colon cancer murine model systems using MALDI MSI. Anal Bioanal Chem 407:2107–2116CrossRefPubMed

40.

Martignoni M, Groothuis GM, de Kanter R (2006) Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction. Expert Opin Drug Metab Toxicol 2:875–894CrossRefPubMed

41.

Chabot GG (1997) Clinical pharmacokinetics of irinotecan. Clin Pharmacokinet 33:245–259CrossRefPubMed

42.

http://pharmacept.com/en/produkte/EmboCept-s-ubersicht/

43.

Pieper CC, Meyer C, Vollmar B, Hauenstein K, Schild HH, Wilhelm KE (2015) Temporary arterial embolization of liver parenchyma with degradable starch microspheres (EmboCept^® S) in a swine model. Cardiovasc Intervent Radiol 38:435–441CrossRefPubMed

44.

Bhutiani N, Akinwande O, Martin RC III (2016) Efficacy and toxicity of hepatic intra-arterial drug-eluting (irinotecan) bead (DEBIRI) therapy in irinotecan-refractory unresectable colorectal liver metastases. World J Surg 40:1178–1190CrossRefPubMed

Titel: Hepatic arterial infusion of irinotecan and EmboCept® S results in high tumor concentration of SN-38 in a rat model of colorectal liver metastases
verfasst von: Anne Kauffels
Marie Kitzmüller
Andrea Gruber
Hannah Nowack
Hanibal Bohnenberger
Melanie Spitzner
Anja Kuthning
Thilo Sprenger
Martin Czejka
Michael Ghadimi
Jens Sperling
Publikationsdatum: 24.01.2019
Verlag: Springer Netherlands
Erschienen in: Clinical & Experimental Metastasis / Ausgabe 1/2019
Print ISSN: 0262-0898
Elektronische ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-019-09954-5

Neu im Fachgebiet Onkologie

23.04.2024 | Medikamente in Schwangerschaft und Stillzeit | Nachrichten

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Hepatic arterial infusion of irinotecan and EmboCept^® S results in high tumor concentration of SN-38 in a rat model of colorectal liver metastases

Abstract

Neu im Fachgebiet Onkologie

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Stufenschema weist Prostatakarzinom zuverlässig nach

Update Onkologie

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2019

Metastasis in the wild: investigating metastasis in non-laboratory animals

Sema4D expression and secretion are increased by HIF-1α and inhibit osteogenesis in bone metastases of lung cancer

Pressurized intraperitoneal aerosol chemotherapy and its effect on gastric-cancer-derived peritoneal metastases: an overview

Correction to: The therapeutic targeting of the FGFR1/Src/NF-κB signaling axis inhibits pancreatic ductal adenocarcinoma stemness and oncogenicity

Frequent discordance in PD-1 and PD-L1 expression between primary breast tumors and their matched distant metastases

Neu im Fachgebiet Onkologie

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Stufenschema weist Prostatakarzinom zuverlässig nach

Update Onkologie