Skip to main content
Top
Published in: Digestive Diseases and Sciences 12/2013

01-12-2013 | Review

Combination Trans Arterial Chemoembolization (TACE) Plus Sorafenib for the Management of Unresectable Hepatocellular Carcinoma: A Systematic Review of the Literature

Authors: O. Abdel-Rahman, Z. A. Elsayed

Published in: Digestive Diseases and Sciences | Issue 12/2013

Login to get access

Abstract

Background

Hepatocellular carcinoma (HCC) is the most common liver neoplasm and the fifth most common cancer worldwide. Intermediate stage HCC [traditionally defined as Barcelona Clinic Liver Cancer (BCLC) B disease and traditionally treated with trans arterial chemoembolization (TACE)] and advanced stage HCC (traditionally defined as BCLC C disease and traditionally treated with sorafenib) are two distinct disease entities with rapidly evolving multimodality treatment approaches. In this systematic review we explore the evidence surrounding the value of using a TACE/sorafenib combination in these two subsets of HCC.

Methods

PubMed, Medline, the Cochrane Library, EMBASE and Google Scholar were searched using the terms “HCC” OR “Hepatoma” or “Liver cancer” AND “TACE” OR “Chemoembolization” AND “Sorafenib” and specifying only English literature. Outcomes of interest included time to progression and overall survival (TTP and OS), tumor response, and toxicities.

Results

A total of 17 potentially relevant trials were identified, of which six studies were excluded. Hence, 11 trials involving 1,000 patients were included, encompassing two phase 1 studies, one phase 3 study, two retrospective analyses and six phase 2 studies. Median TTP was reported in five out of 11 studies and it ranged from 6.3 to 9.0 months. Median OS was reported in five out of 11 studies and it was similarly variable as PFS, ranging from 12 to 29 months. The DCR (disease control rate) was reported in eight out of 11 studies, ranging from 32 to 95 %. Frequently reported grade 3/4 toxicities were increased aspartate transaminase/alanine transaminase, fatigue, hypertension, hand-foot skin reaction and diarrhea.

Conclusions

The sorafenib/TACE combination shows promise as an effective and tolerable treatment strategy for intermediate stage/advanced HCC. The reported efficacy of a sorafenib/TACE combination appears to compare favorably with sorafenib or TACE monotherapies, the most commonly implemented strategies for unresectable HCC. Further clinical studies are warranted to accurately determine which patients are expected to benefit most from such combination strategies.
Literature
1.
go back to reference Graham J, Newman D, Smirniotopolous J, et al. Transplantation for hepatocellular carcinoma in younger patients has an equivocal survival advantage as compared with resection. Transpl Proc. 2013;45:265–271.CrossRef Graham J, Newman D, Smirniotopolous J, et al. Transplantation for hepatocellular carcinoma in younger patients has an equivocal survival advantage as compared with resection. Transpl Proc. 2013;45:265–271.CrossRef
2.
go back to reference Schiefelbein E, Zekri AR, Newton DW, et al. Hepatitis C virus and other risk factors in hepatocellular carcinoma. Acta Virol. 2012;56:235–240.PubMedCrossRef Schiefelbein E, Zekri AR, Newton DW, et al. Hepatitis C virus and other risk factors in hepatocellular carcinoma. Acta Virol. 2012;56:235–240.PubMedCrossRef
3.
go back to reference Okuda K, Ohtsuki T, Obata H, et al. Natural history of hepatocellular carcinoma and prognosis in relation to treatment; study of 850 patients. Cancer. 1985;56:918–928.PubMedCrossRef Okuda K, Ohtsuki T, Obata H, et al. Natural history of hepatocellular carcinoma and prognosis in relation to treatment; study of 850 patients. Cancer. 1985;56:918–928.PubMedCrossRef
5.
go back to reference Levy I, Sherman M. Staging of hepatocellular carcinoma: assessment of the CLIP, Okuda, and Child-Pugh staging systems in a cohort of 257 patients in Toronto. Gut. 2002;50:881–885.PubMedCrossRef Levy I, Sherman M. Staging of hepatocellular carcinoma: assessment of the CLIP, Okuda, and Child-Pugh staging systems in a cohort of 257 patients in Toronto. Gut. 2002;50:881–885.PubMedCrossRef
6.
go back to reference Forner A, Hessheimer AJ, Isabel Real M, et al. Treatment of hepatocellular carcinoma. Crit Rev Oncol Hematol. 2006;60:89–98.PubMedCrossRef Forner A, Hessheimer AJ, Isabel Real M, et al. Treatment of hepatocellular carcinoma. Crit Rev Oncol Hematol. 2006;60:89–98.PubMedCrossRef
8.
go back to reference Yau T, Chan P, Epstein R, et al. Evolution of systemic therapy of advanced hepatocellular carcinoma. World J Gastroenterol. 2008;14:6437–6441.PubMedCrossRef Yau T, Chan P, Epstein R, et al. Evolution of systemic therapy of advanced hepatocellular carcinoma. World J Gastroenterol. 2008;14:6437–6441.PubMedCrossRef
9.
10.
go back to reference Li X, Feng G, Zheng C, et al. Expression of plasma vascular endothelial growth factor in patients with hepatocellular carcinoma and effect of transcatheter arterial chemoembolization therapy on plasma vascular endothelial growth factor level. World J Gastroenterol. 2004;10:2878–2882.PubMed Li X, Feng G, Zheng C, et al. Expression of plasma vascular endothelial growth factor in patients with hepatocellular carcinoma and effect of transcatheter arterial chemoembolization therapy on plasma vascular endothelial growth factor level. World J Gastroenterol. 2004;10:2878–2882.PubMed
11.
go back to reference Chung YH, Han G, Yoon JH, et al. Interim analysis of START: study in Asia of the combination of TACE (transcatheter arterial chemoembolization) with sorafenib in patients with hepatocellular carcinoma trial. Int J Cancer. 2013;132:2448–2458. doi:10.1002/ijc.27925.PubMedCrossRef Chung YH, Han G, Yoon JH, et al. Interim analysis of START: study in Asia of the combination of TACE (transcatheter arterial chemoembolization) with sorafenib in patients with hepatocellular carcinoma trial. Int J Cancer. 2013;132:2448–2458. doi:10.​1002/​ijc.​27925.PubMedCrossRef
12.
go back to reference Sansonno D, Lauletta G, Russi S, et al. Transarterial chemoembolization plus sorafenib: a sequential therapeutic scheme for HCV-related intermediate-stage hepatocellular carcinoma: a randomized clinical trial. Oncologist. 2012;17:359–366. doi:10.1634/theoncologist.2011-0313.PubMedCrossRef Sansonno D, Lauletta G, Russi S, et al. Transarterial chemoembolization plus sorafenib: a sequential therapeutic scheme for HCV-related intermediate-stage hepatocellular carcinoma: a randomized clinical trial. Oncologist. 2012;17:359–366. doi:10.​1634/​theoncologist.​2011-0313.PubMedCrossRef
14.
go back to reference Sieghart W, Pinter M, Reisegger M, et al. Conventional transarterial chemoembolisation in combination with sorafenib for patients with hepatocellular carcinoma: a pilot study. Eur Radiol. 2012;22(6):1214–1223. doi:10.1007/s00330-011-2368-z.PubMedCrossRef Sieghart W, Pinter M, Reisegger M, et al. Conventional transarterial chemoembolisation in combination with sorafenib for patients with hepatocellular carcinoma: a pilot study. Eur Radiol. 2012;22(6):1214–1223. doi:10.​1007/​s00330-011-2368-z.PubMedCrossRef
15.
16.
17.
go back to reference Qu XD, Chen CS, Wang JH, et al. The efficacy of TACE combined sorafenib in advanced stages hepatocellullar carcinoma. BMC Cancer. 2012;12:263.PubMedCrossRef Qu XD, Chen CS, Wang JH, et al. The efficacy of TACE combined sorafenib in advanced stages hepatocellullar carcinoma. BMC Cancer. 2012;12:263.PubMedCrossRef
18.
go back to reference Zhao Y, Wang WJ, Guan S, et al. Sorafenib combined with transarterial chemoembolization for the treatment of advanced hepatocellular carcinoma: a large-scale multicenter study of 222 patients. Ann Oncol. 2013;24:1786–1792. doi:10.1093/annonc/mdt072.PubMedCrossRef Zhao Y, Wang WJ, Guan S, et al. Sorafenib combined with transarterial chemoembolization for the treatment of advanced hepatocellular carcinoma: a large-scale multicenter study of 222 patients. Ann Oncol. 2013;24:1786–1792. doi:10.​1093/​annonc/​mdt072.PubMedCrossRef
20.
go back to reference Bai W, Wang YJ, Zhao Y, et al. Sorafenib in combination with transarterial chemoembolization improves the survival of patients with unresectable hepatocellular carcinoma: a propensity score matching study. J Dig Dis. 2013;14:181–190. doi:10.1111/1751-2980.12038.PubMedCrossRef Bai W, Wang YJ, Zhao Y, et al. Sorafenib in combination with transarterial chemoembolization improves the survival of patients with unresectable hepatocellular carcinoma: a propensity score matching study. J Dig Dis. 2013;14:181–190. doi:10.​1111/​1751-2980.​12038.PubMedCrossRef
22.
go back to reference Raoul JL, Sangro B, Forner A, et al. Evolving strategies for the management of intermediate-stage hepatocellular carcinoma: available evidence and expert opinion on the use of transarterial chemoembolization. Cancer Treat Rev. 2011;37:212–20. Raoul JL, Sangro B, Forner A, et al. Evolving strategies for the management of intermediate-stage hepatocellular carcinoma: available evidence and expert opinion on the use of transarterial chemoembolization. Cancer Treat Rev. 2011;37:212–20.
23.
go back to reference GETCH. A comparison of lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma. Groupe d’Etude et de Traitement du Carcinome Hépatocellulaire. N Engl J Med. 1995;332:1256–1261.CrossRef GETCH. A comparison of lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma. Groupe d’Etude et de Traitement du Carcinome Hépatocellulaire. N Engl J Med. 1995;332:1256–1261.CrossRef
24.
go back to reference Pelletier G, Ducreux M, Gay F, et al. Treatment of unresectable hepatocellular carcinoma with lipiodol chemoembolization: a multicenter randomized trial. Groupe CHC. J Hepatol. 1998;29:129–134.PubMedCrossRef Pelletier G, Ducreux M, Gay F, et al. Treatment of unresectable hepatocellular carcinoma with lipiodol chemoembolization: a multicenter randomized trial. Groupe CHC. J Hepatol. 1998;29:129–134.PubMedCrossRef
25.
go back to reference Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology. 2003;37:429–442.PubMedCrossRef Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology. 2003;37:429–442.PubMedCrossRef
26.
go back to reference Liovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–390.CrossRef Liovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–390.CrossRef
27.
go back to reference Cheng AL, Kang YK, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10:25–34.PubMedCrossRef Cheng AL, Kang YK, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10:25–34.PubMedCrossRef
Metadata
Title
Combination Trans Arterial Chemoembolization (TACE) Plus Sorafenib for the Management of Unresectable Hepatocellular Carcinoma: A Systematic Review of the Literature
Authors
O. Abdel-Rahman
Z. A. Elsayed
Publication date
01-12-2013
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 12/2013
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-013-2872-x

Other articles of this Issue 12/2013

Digestive Diseases and Sciences 12/2013 Go to the issue