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Erschienen in: CardioVascular and Interventional Radiology 8/2017

17.03.2017 | Laboratory Investigation

New Interventional Treatment Model for Pancreatic Neoplasms Using Gemcitabine-Eluting Hydrogel Devices: In Vitro and In Vivo Results

verfasst von: Ruben Lopez-Benitez, David Benz, Yue Wu, Xinping Wu, Samuel Chen, Gregory M. Cruise

Erschienen in: CardioVascular and Interventional Radiology | Ausgabe 8/2017

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Abstract

Objectives

In vitro and in vivo evaluation of fast- and slow-release gemcitabine-eluting hydrogel (GEH) devices.

Methods

For in vitro elution, the GEH devices were placed in phosphate-buffered saline at 37 °C. Periodically, the solution was analyzed for gemcitabine. The devices consisting of fast release (n = 8), slow release (n = 6), or bland (n = 4) were delivered through a 5-Fr catheter into the gastroduodenal artery of a pig. Additionally, four pigs were treated with intravenous (IV) injection of gemcitabine. Pigs were killed at day 1 (n = 9), day 7 (n = 11), or day 21 (n = 2). Gemcitabine concentrations in the plasma and tissues were determined.

Results

In vitro, gemcitabine was completely eluted within 6 h or 30 days for the fast- and slow-release devices, respectively. All 22 pigs were treated without morbidity or mortality. Gemcitabine plasma concentrations peaked at about 105,000 ± 30,000, 252 ± 101, 22 ± 29, and 0 ± 0 ppb for the IV, fast-release, slow-release, and bland treatments, respectively. At days 1 and 7, gemcitabine concentrations were higher in the pancreas for the GEH devices than IV. Gemcitabine delivery to the pancreas was sustained over 21 days in the slow-release group.

Conclusions

Treatment with GEH devices resulted in at least equivalent gemcitabine concentration in the pancreas and reduced concentration in the plasma, heart, liver, and duodenum, at least equivalent to IV injection and reduced concentrations elsewhere. These results show the potential of sustained local delivery of gemcitabine to treat pancreatic neoplasms with reduced side effects.
Literatur
1.
Zurück zum Zitat Hackert T, Buchler MW. Pancreatic cancer: advances in treatment, results and limitations. Dig Dis. 2013;31(1):51–6.CrossRefPubMed Hackert T, Buchler MW. Pancreatic cancer: advances in treatment, results and limitations. Dig Dis. 2013;31(1):51–6.CrossRefPubMed
2.
Zurück zum Zitat Ethun CG, Kooby DA. The importance of surgical margins in pancreatic cancer. J Surg Oncol. 2015. Ethun CG, Kooby DA. The importance of surgical margins in pancreatic cancer. J Surg Oncol. 2015.
3.
Zurück zum Zitat Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–25.CrossRefPubMed Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–25.CrossRefPubMed
4.
Zurück zum Zitat Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691–703.CrossRef Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691–703.CrossRef
5.
Zurück zum Zitat Borad MJ, Reddy SG, Bahary N, et al. Randomized phase II trial of gemcitabine plus TH-302 versus gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2015;33(13):1475–81.CrossRefPubMed Borad MJ, Reddy SG, Bahary N, et al. Randomized phase II trial of gemcitabine plus TH-302 versus gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2015;33(13):1475–81.CrossRefPubMed
6.
Zurück zum Zitat Laheru D, Lutz E, Burke J, et al. Allogeneic granulocyte macrophage colony-stimulating factor-secreting tumor immunotherapy alone or in sequence with cyclophosphamide for metastatic pancreatic cancer: a pilot study of safety, feasibility, and immune activation. Clin Cancer Res. 2008;14(5):1455–63.CrossRefPubMedPubMedCentral Laheru D, Lutz E, Burke J, et al. Allogeneic granulocyte macrophage colony-stimulating factor-secreting tumor immunotherapy alone or in sequence with cyclophosphamide for metastatic pancreatic cancer: a pilot study of safety, feasibility, and immune activation. Clin Cancer Res. 2008;14(5):1455–63.CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Ierardi AM, Lucchina N, Bacuzzi A, et al. Percutaneous ablation therapies of inoperable pancreatic cancer: a systematic review. Ann Gastroenterol. 2015;28(4):431–9.PubMedPubMedCentral Ierardi AM, Lucchina N, Bacuzzi A, et al. Percutaneous ablation therapies of inoperable pancreatic cancer: a systematic review. Ann Gastroenterol. 2015;28(4):431–9.PubMedPubMedCentral
8.
Zurück zum Zitat Su TS, Liang P, Lu HZ, et al. Stereotactic body radiotherapy using CyberKnife for locally advanced unresectable and metastatic pancreatic cancer. World J Gastroenterol. 2015;21(26):8156–62.CrossRefPubMedPubMedCentral Su TS, Liang P, Lu HZ, et al. Stereotactic body radiotherapy using CyberKnife for locally advanced unresectable and metastatic pancreatic cancer. World J Gastroenterol. 2015;21(26):8156–62.CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Martin RC 2nd, Kwon D, Chalikonda S, et al. Treatment of 200 locally advanced (stage III) pancreatic adenocarcinoma patients with irreversible electroporation: safety and efficacy. Ann Surg. 2015;262(3):486–94 (discussion 492–484).CrossRefPubMed Martin RC 2nd, Kwon D, Chalikonda S, et al. Treatment of 200 locally advanced (stage III) pancreatic adenocarcinoma patients with irreversible electroporation: safety and efficacy. Ann Surg. 2015;262(3):486–94 (discussion 492–484).CrossRefPubMed
10.
Zurück zum Zitat Lammer J, Malagari K, Vogl T, et al. Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Interv Radiol. 2010;33(1):41–52.CrossRef Lammer J, Malagari K, Vogl T, et al. Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Interv Radiol. 2010;33(1):41–52.CrossRef
11.
Zurück zum Zitat She WH, Chan AC, Cheung TT, et al. Acute pancreatitis induced by transarterial chemoembolization: a single-center experience of over 1500 cases. Hepatobiliary Pancreat Dis Int. 2016;15(1):93–8.CrossRefPubMed She WH, Chan AC, Cheung TT, et al. Acute pancreatitis induced by transarterial chemoembolization: a single-center experience of over 1500 cases. Hepatobiliary Pancreat Dis Int. 2016;15(1):93–8.CrossRefPubMed
12.
Zurück zum Zitat Constant MJ, Keeley EM, Cruise GM. Preparation, characterization, and evaluation of radiopaque hydrogel filaments for endovascular embolization. J Biomed Mater Res B Appl Biomater. 2009;89(2):306–13.CrossRefPubMed Constant MJ, Keeley EM, Cruise GM. Preparation, characterization, and evaluation of radiopaque hydrogel filaments for endovascular embolization. J Biomed Mater Res B Appl Biomater. 2009;89(2):306–13.CrossRefPubMed
13.
Zurück zum Zitat Lopez-Benitez R, Hallscheidt P, Kratochwil C, et al. Protective embolization of the gastroduodenal artery with a one-HydroCoil technique in radioembolization procedures. Cardiovasc Interv Radiol. 2013;36(1):105–10.CrossRef Lopez-Benitez R, Hallscheidt P, Kratochwil C, et al. Protective embolization of the gastroduodenal artery with a one-HydroCoil technique in radioembolization procedures. Cardiovasc Interv Radiol. 2013;36(1):105–10.CrossRef
14.
Zurück zum Zitat Martin RC, Joshi J, Robbins K, Tomalty D, O’Hara R, Tatum C. Transarterial chemoembolization of metastatic colorectal carcinoma with drug-eluting beads, irinotecan (DEBIRI): multi-institutional registry. J Oncol. 2009;2009:539795.CrossRefPubMedPubMedCentral Martin RC, Joshi J, Robbins K, Tomalty D, O’Hara R, Tatum C. Transarterial chemoembolization of metastatic colorectal carcinoma with drug-eluting beads, irinotecan (DEBIRI): multi-institutional registry. J Oncol. 2009;2009:539795.CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Rott G, Biggemann M, Pfohl M. Embolization of an insulinoma of the pancreas with trisacryl gelatin microspheres as definitive treatment. Cardiovasc Interv Radiol. 2008;31(3):659–62.CrossRef Rott G, Biggemann M, Pfohl M. Embolization of an insulinoma of the pancreas with trisacryl gelatin microspheres as definitive treatment. Cardiovasc Interv Radiol. 2008;31(3):659–62.CrossRef
16.
Zurück zum Zitat Rao PP, Pascale F, Seck A, et al. Irinotecan loaded in eluting beads: preclinical assessment in a rabbit VX2 liver tumor model. Cardiovasc Interv Radiol. 2012;35(6):1448–59.CrossRef Rao PP, Pascale F, Seck A, et al. Irinotecan loaded in eluting beads: preclinical assessment in a rabbit VX2 liver tumor model. Cardiovasc Interv Radiol. 2012;35(6):1448–59.CrossRef
17.
Zurück zum Zitat Olive KP, Jacobetz MA, Davidson CJ, et al. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science. 2009;324(5933):1457–61.CrossRefPubMedPubMedCentral Olive KP, Jacobetz MA, Davidson CJ, et al. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science. 2009;324(5933):1457–61.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Jordan O, Denys A, De Baere T, Boulens N, Doelker E. Comparative study of chemoembolization loadable beads: in vitro drug release and physical properties of DC bead and hepasphere loaded with doxorubicin and irinotecan. J Vasc Interv Radiol. 2010;21(7):1084–90.CrossRefPubMed Jordan O, Denys A, De Baere T, Boulens N, Doelker E. Comparative study of chemoembolization loadable beads: in vitro drug release and physical properties of DC bead and hepasphere loaded with doxorubicin and irinotecan. J Vasc Interv Radiol. 2010;21(7):1084–90.CrossRefPubMed
19.
Zurück zum Zitat Taylor RR, Tang Y, Gonzalez MV, Stratford PW, Lewis AL. Irinotecan drug eluting beads for use in chemoembolization: in vitro and in vivo evaluation of drug release properties. Eur J Pharm Sci. 2007;30(1):7–14.CrossRefPubMed Taylor RR, Tang Y, Gonzalez MV, Stratford PW, Lewis AL. Irinotecan drug eluting beads for use in chemoembolization: in vitro and in vivo evaluation of drug release properties. Eur J Pharm Sci. 2007;30(1):7–14.CrossRefPubMed
20.
Zurück zum Zitat Guiu B, Schmitt A, Reinhardt S, et al. Idarubicin-loaded ONCOZENE drug-eluting embolic agents for chemoembolization of hepatocellular carcinoma: in vitro loading and release and in vivo pharmacokinetics. J Vasc Interv Radiol. 2015;26(2):262–70.CrossRefPubMed Guiu B, Schmitt A, Reinhardt S, et al. Idarubicin-loaded ONCOZENE drug-eluting embolic agents for chemoembolization of hepatocellular carcinoma: in vitro loading and release and in vivo pharmacokinetics. J Vasc Interv Radiol. 2015;26(2):262–70.CrossRefPubMed
Metadaten
Titel
New Interventional Treatment Model for Pancreatic Neoplasms Using Gemcitabine-Eluting Hydrogel Devices: In Vitro and In Vivo Results
verfasst von
Ruben Lopez-Benitez
David Benz
Yue Wu
Xinping Wu
Samuel Chen
Gregory M. Cruise
Publikationsdatum
17.03.2017
Verlag
Springer US
Erschienen in
CardioVascular and Interventional Radiology / Ausgabe 8/2017
Print ISSN: 0174-1551
Elektronische ISSN: 1432-086X
DOI
https://doi.org/10.1007/s00270-017-1627-z

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