Modified transarterial chemoembolization with locoregional administration of sorafenib for treating hepatocellular carcinoma: feasibility, efficacy, and safety in the VX-2 rabbit liver tumor model

PURPOSE We aimed to assess the feasibility, efficacy and safety of a local application of sorafenib within a conventional transarterial chemoembolization in the VX-2 tumor-bearing rabbit model. METHODS VX-2 tumors were induced in the left liver lobe of 10 New Zealand White rabbits. After two weeks, growth was verified by contrast-enhanced computed tomography (CT). Five rabbits were treated by transarterial chemoembolization using an emulsion of sorafenib and ethiodized oil (referred to as SORATACE; n=5). Rabbits receiving oral sorafenib for two weeks (n=2) and untreated rabbits (n=3) served as controls. After two weeks, contrast-enhanced CT was performed, followed by animal necropsy. RESULTS The change in tumor diameter between baseline and follow-up was significantly different in the SORATACE group compared with the other groups; tumor shrinkage was observed in the SORATACE group only (P = 0.016). In both control groups, preserved hypervascularity was seen in the follow-up CT in all but one tumor. All tumors in the SORATACE group were devascularized in the follow-up CT. Importantly, substantial parenchymal damage in nontargeted areas of the tumor-bearing liver lobe was seen in rabbits treated with SORATACE. CONCLUSION SORATACE demonstrated high efficacy in the treatment of experimental VX-2 liver tumors but was also associated with substantial liver parenchymal toxicity.

Kaynakça

Bruix J, Sherman M. Management of hepa- tocellular carcinoma: an update. Hepatology 2011; 3:1020-1022. [CrossRef]

Llovet JM, Di Bisceglie AM, Bruix J, et al. Design and endpoints of clinical trials in hepatocellu- lar carcinoma. J Natl Cancer Inst 2008; 10:698- 711. [CrossRef]

Mazzaferro V, Regalia E, Doci R, et al. Liver trans- plantation for the treatment of small hepato- cellular carcinomas in patients with cirrhosis. N Engl J Med 1996; 11:693-699. [CrossRef]

Wang Y, Luo Q, Li Y, Deng S, Wei S, Li X. Radiof- requency ablation versus hepatic resection for small hepatocellular carcinomas: a meta-analysis of randomized and nonrandomized controlled trials. PLoS One 2014; 1:e84484. [CrossRef]

Hu HT, Kim JH, Lee LS, et al. Chemoemboliza- tion for hepatocellular carcinoma: multivariate analysis of predicting factors for tumor re- sponse and survival in a 362-patient cohort. J Vasc Interv Radiol 2011; 7:917-923. [CrossRef]

Llovet JM, Real MI, Montana X, et al. Arterial embo- lisation or chemoembolisation versus symptomat- ic treatment in patients with unresectable hepato- cellular carcinoma: a randomised controlled trial. Lancet 2002; 9319:1734-1739. [CrossRef]

Lo CM, Ngan H, Tso WK, et al. Randomized con- trolled trial of transarterial lipiodol chemoembo- lization for unresectable hepatocellular carcino- ma. Hepatology 2002; 5:1164-1171. [CrossRef]

Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 4:378-390. [CrossRef]

Chen CH, Hu FC, Huang GT, et al. Applicability of staging systems for patients with hepato- cellular carcinoma is dependent on treatment method--analysis of 2010 Taiwanese patients. Eur J Cancer 2009; 9:1630-1639. [CrossRef]

Lewandowski RJ, Mulcahy MF, Kulik LM, et al. Chemoembolization for hepatocellular carci- noma: comprehensive imaging and survival analysis in a 172-patient cohort. Radiology 2010; 3:955-965. [CrossRef]

Sangro B, Carpanese L, Cianni R, et al. Survival after yttrium-90 resin microsphere radioemboli- zation of hepatocellular carcinoma across Barce- lona clinic liver cancer stages: a European evalua- tion. Hepatology 2011; 3:868-878. [CrossRef]

Wang JH, Changchien CS, Hu TH, et al. The efficacy of treatment schedules according to Barcelona Clinic Liver Cancer staging for hepatocellular car- cinoma - Survival analysis of 3892 patients. Eur J Cancer 2008; 7:1000-1006. [CrossRef]

Kim YB, Park YN, Park C. Increased proliferation activities of vascular endothelial cells and tu- mour cells in residual hepatocellular carcinoma following transcatheter arterial embolization. Histopathology 2001; 2:160-166. [CrossRef]

Wang B, Xu H, Gao ZQ, Ning HF, Sun YQ, Cao GW. Increased expression of vascular endothe- lial growth factor in hepatocellular carcinoma after transcatheter arterial chemoemboliza- tion. Acta Radiol 2008; 5:523-529. [CrossRef]

Lencioni R, Zou J, Leberre M, et al. Sorafenib (SOR) or placebo (PL) in combination with transarterial chemoembolization (TACE) for intermediate-stage hepatocellular carcinoma (SPACE). J Clin Oncology 28:15s, 2010 (suppl; abstr TPS178) ed, 2012. 2012.

Liu L, Chen H, Wang M, et al. Combination ther- apy of sorafenib and TACE for unresectable HCC: a systematic review and meta-analysis. PLoS One 2014; 3:e91124. [CrossRef]

Zhang L, Hu P, Chen X, Bie P. Transarterial chemoembolization (TACE) plus sorafenib ver- sus TACE for intermediate or advanced stage hepatocellular carcinoma: a meta-analysis. PLoS One 2014; 6:e100305. [CrossRef]

Ricke J, Bulla K, Kolligs F, et al. Safety and toxic- ity of radioembolization plus Sorafenib in ad- vanced hepatocellular carcinoma: analysis of the European multicentre trial SORAMIC. Liver Int 2015; 35:620-626. [CrossRef]

Gaba RC, Yap FY, Martinez EM, et al. Transarte- rial sorafenib chemoembolization: preliminary study of technical feasibility in a rabbit model. J Vasc Interv Radiol 2013; 5:744-750. [CrossRef]

Chatziioannou AN, Siskos AP, Loxas D, et al. Transarterial embolization with sorafenib in animal livers: a pharmacokinetics study. J Vasc Interv Radiol 2013; 11:1657-1663. [CrossRef]

Geschwind JF, Artemov D, Abraham S, et al. Chemoembolization of liver tumor in a rabbit model: assessment of tumor cell death with diffu- sion-weighted MR imaging and histologic analysis. J Vasc Interv Radiol 2000; 10:1245-1255. [CrossRef]

Lee KH, Liapi E, Ventura VP, et al. Evaluation of different calibrated spherical polyvinyl alcohol microspheres in transcatheter arterial chemo- embolization: VX2 tumor model in rabbit liver. J Vasc Interv Radiol 2008; 7:1065-1069. [CrossRef]

Lin WY, Chen J, Lin Y, Han K. Implantation of VX2 carcinoma into the liver of rabbits: a com- parison of three direct-injection methods. J Vet Med Sci 2002; 7:649-652. [CrossRef]

Lewandowski RJ, Geschwind JF, Liapi E, Salem R. Transcatheter intraarterial therapies: rationale and overview. Radiology 2011; 3:641-657. [CrossRef]

Deng G, Zhao DL, Li GC, Yu H, Teng GJ. Combi- nation therapy of transcatheter arterial chemo- embolization and arterial administration of an- tiangiogenesis on VX2 liver tumor. Cardiovasc Intervent Radiol 2011; 4:824-832. [CrossRef]

Strumberg D, Clark JW, Awada A, et al. Safety, pharmacokinetics, and preliminary antitumor activity of sorafenib: a review of four phase I trials in patients with advanced refractory solid tumors. Oncologist 2007; 4:426-437. [CrossRef]

Strumberg D, Richly H, Hilger RA, et al. Phase I clinical and pharmacokinetic study of the Nov- el Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43-9006 in pa- tients with advanced refractory solid tumors. J Clin Oncol 2005; 5:965-972.

Sieghart W, Hucke F, Pinter M, et al. The ART of deci- sion making: retreatment with transarterial chemo- embolization in patients with hepatocellular carci- noma. Hepatology 2013; 6:2261-2273. [CrossRef]

Hong K, Kobeiter H, Georgiades CS, Torbenson MS, Geschwind JF. Effects of the type of emboliza- tion particles on carboplatin concentration in liver tumors after transcatheter arterial chemoemboli- zation in a rabbit model of liver cancer. J Vasc In- terv Radiol 2005; 12:1711-1717. [CrossRef]

Yoon CJ, Chung JW, Park JH, et al. Transcatheter arterial embolization with 188Rhenium-HDD-la- beled iodized oil in rabbit VX2 liver tumor. J Vasc Interv Radiol 2004; 10:1121-1128. [CrossRef]

Aravalli RN, Steer CJ, Sahin MB, Cressman EN. Stem cell origins and animal models of hepatocellular car- cinoma. Dig Dis Sci 2010; 5:1241-1250. [CrossRef]

Rous P, Beard JW. A virus-induced mammali- an growth with the characters of a tumor (the shope rabbit papilloma): I. the growth on im- plantation within favorable hosts. J Exp Med 1934; 6:701-722. [CrossRef]

Pauser S, Wagner S, Lippmann M, et al. Eval- uation of efficient chemoembolization mix- tures by magnetic resonance imaging thera- py monitoring: an experimental study on the VX2 tumor in the rabbit liver. Cancer Res 1996; 8:1863-1867.

Ko YH, Pedersen PL, Geschwind JF. Glucose ca- tabolism in the rabbit VX2 tumor model for liv- er cancer: characterization and targeting hex- okinase. Cancer Lett 2001; 1:83-91. [CrossRef]

Kaynak Göster

1404 1029

Arşiv
Sayıdaki Diğer Makaleler

Treatment of acute thoracic aortic syndromes using endovascular techniques

Emrah UĞUZ, MURAT CANYİĞİT, METE HIDIROĞLU, Erol ŞENER

The role of coronary CT angiography in diagnosis of patent foramen ovale

Kemal KARA, Ali Kemal SİVRİOĞLU, Ersin ÖZTÜRK, MEHMET İNCEDAYI, Muzaffer SAGLAM, Serkan ARIBAL, ZAFER IŞILAK, HAKAN MUTLU

Modified transarterial chemoembolization with locoregional administration of sorafenib for treating hepatocellular carcinoma: feasibility, efficacy, and safety in the VX-2 rabbit liver tumor model

Max SEİDENSTİCKER, Sebastian STREİT, Norbert NASS, Christian WYBRANSKİ, Julian JÜRGENS, Jan BRAUNER, Nadine SCHULZ, Thomas KALİNSKİ, Ricarda SEİDENSTİCKER, Benjamin GARLİPP, Ingo STEFFEN, Jens RİCKE, Oliver DUDECK

Transcatheter arterial embolization for traumatic mesenteric bleeding: a 15-year, single-center experience

Jong Soo SHİN, Ji Hoon SHİN, Heung-Kyu KO, Jong Woo KİM, Hyun-Ki YOON

Coronary lesion complexity assessed by SYNTAX score in 256-slice dual-source MDCT angiography

Zeyneb YÜCELER, Mecit KANTARCI, İbrahim Halil TANBOĞA, RECEP SADE, Yeşim KIZRAK, RÜSTEM BERHAN PİRİMOĞLU, ÜMMÜGÜLSÜM BAYRAKTUTAN, Hayri OĞUL, ENBİYA AKSAKAL

MRI anatomy of parametrial extension to better identify local pathways of disease spread in cervical cancer

Anna Lia VALENTİNİ, Benedetta GUİ, Maura MİCCÒ, Michela GİULİANİ, Elena RODOLFİNO, Valeria NİNİVAGGİ, Marta IACOBUCCİ, Marzia MARİNO, Maria Antonietta GAMBACORTA, Antonia Carla TESTA, Gian Franco ZANNONİ, Lorenzo BONOMO

Use of MRI to identify enlarged inferior gluteal and ischioanal lymph nodes and associated findings related to the primary disease

ÇAĞLAR UZUN, GÜL AYŞE ERDEN, EBRU DÜŞÜNCELİ ATMAN, EVREN ÜSTÜNER

Persistence of pulmonary arteriovenous malformations after successful embolotherapy with Amplatzer vascular plug: long-term results

Ahmed Kamel ABDEL-AA, Rafik Mohamed IBRAHİM, Amr Soliman MOUSTAFA, Maysoon Farouk HAMED, Souheil SADDEKNİ

Feasibility of histogram analysis of susceptibility-weighted MRI for staging of liver fibrosis

Zhao-Xia YANG, He-Yue LİANG, Xin-Xing HU, Ya-Qin HUANG, Ying DİNG, Shan YANG, Meng-Su ZENG, Sheng-Xiang RAO

Splenic artery embolization with Ankaferd blood stopper in a sheep model

OSMAN KOÇ, Kadir ACAR, Orhan ÖZBEK, İbrahim GÜLER, ZÜLFÜKAR KADİR SARITAŞ, Tuba Bera ERDEM, Yalçın SOLAK, Hatice TOY, Ahmet KÜÇÜKAPAN, Seda ÖZBEK, Abduzhappar GAIPOV, İbrahim C. HAZNEDAROĞLU