Efficacy and adverse events of transcatheter arterial chemoembolization in combination with sorafenib in the treatment of unresectable hepatocellular carcinoma

Yao,Xuesong; Yan,Dong; Liu,Dezhong; Zeng,Huiying; Li,Huai

doi:10.3892/mco.2015.554

Efficacy and adverse events of transcatheter arterial chemoembolization in combination with sorafenib in the treatment of unresectable hepatocellular carcinoma

Authors:
- Xuesong Yao
- Dong Yan
- Dezhong Liu
- Huiying Zeng
- Huai Li
View Affiliations

Affiliations: Department of Diagnostic Radiology, Cancer Hospital, Chinese Academy of Medical Science, Peking Union Medical College, Beijing 100005, P.R. China
Published online on: April 24, 2015 https://doi.org/10.3892/mco.2015.554
Pages: 929-935

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to assess the association between the efficacy and adverse events (AEs) of transcatheter arterial chemoembolization (TACE) combined with sorafenib in patients with unresectable hepatocellular carcinoma (HCC). Between July 2008 and May 2011, 50 patients with unresectable HCC were enrolled and assigned to receive TACE combined with sorafenib in the present study. The primary outcomes were considered as time to disease progression (TTP) and sorafenib‑related AEs. In the present study, 34 of 50 patients had disease progression with a median TTP (mTTP) of 210 days. The most common AEs included hand‑foot skin reaction (HFSR), fatigue, diarrhea and hypertension. The mTTP of patients with HFSR extended 140 days compared to that of the patients without HFSR. Kaplan‑Meier analysis was used for mTTP between the two groups of patients. This difference was statistically significant when analyzed by the univariate COX proportional hazards regression model. In conclusion, TACE in combination with sorafenib had an acceptable safety profile in the treatment of unresectable HCC. Additionally, it also revealed that HFSR served as a good prognostic predictor in using combination therapy. Therefore, discontinuation of sorafenib treatment should be prevented to avoid disease progression.

View Figures

View References

1	Llovet JM and Bruix J: Novel advancements in the management of hepatocellular carcinoma in 2008. J Hepatol. 48:(Suppl 1). 20–37. 2008. View Article : Google Scholar : PubMed/NCBI
2	Marelli L, Stigliano R, Triantos C, et al: Transarterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies. Cardiovasc Intervent Radiol. 30:6–25. 2007. View Article : Google Scholar : PubMed/NCBI
3	Llovet JM and Bruix J: Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology. 37:429–442. 2003. View Article : Google Scholar : PubMed/NCBI
4	Llovet JM, Real MI, Montana X, et al: Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 359:1734–1739. 2002. View Article : Google Scholar : PubMed/NCBI
5	Sergio A, Cristofori C, Cardin R, et al: Transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): the role of angiogenesis and invasiveness. Am J Gastroenterol. 103:914–921. 2008. View Article : Google Scholar : PubMed/NCBI
6	Dufour JF, Hoppe H, Heim MH, et al: Continuous administration of sorafenib in combination with transarterial chemoembolization in patients with hepatocellular carcinoma: results of a phase I study. Oncologist. 15:1198–1204. 2010. View Article : Google Scholar : PubMed/NCBI
7	Eisenhauer EA, Therasse P, Bogaerts J, et al: New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 45:228–247. 2009. View Article : Google Scholar : PubMed/NCBI
8	Zhijun W and Maoqiang W: Combination of TACE with molecularly targeted agent in management of advanced HCC. Int J Med Radiol. 32:374–377. 2009.
9	Enhua X: Pathological changes of molecular biology in treatment of liver cancer with TACE. CJIR. 2:132–135. 2008.
10	Shim JH, Park JW, Kim JH, et al: Association between increment of serum VEGF level and prognosis after transcatheter arterial chemoembolization in hepatocellular carcinoma patients. Cancer Sci. 99:2037–2044. 2008.PubMed/NCBI
11	von Marschall Z, Cramer T, Hocker M, Finkenzeller G, Wiedenmann B and Rosewicz S: Dual mechanism of vascular endothelial growth factor upregulation by hypoxia in human hepatocellular carcinoma. Gut. 48:87–96. 2001. View Article : Google Scholar : PubMed/NCBI
12	Wilhelm SM, Carter C, Tang L, et al: BAY 43–9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 64:7099–7109. 2004. View Article : Google Scholar : PubMed/NCBI
13	Chang YS, Adnane J, Trail PA, et al: Sorafenib (BAY 43–9006) inhibits tumor growth and vascularization and induces tumor apoptosis and hypoxia in RCC xenograft models. Cancer Chemother Pharmacol. 59:561–574. 2007. View Article : Google Scholar : PubMed/NCBI
14	Llovet JM, Ricci S, Mazzaferro V, et al: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 359:378–390. 2008. View Article : Google Scholar : PubMed/NCBI
15	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. 10:25–34. 2009. View Article : Google Scholar : PubMed/NCBI
16	Strebel BM and Dufour JF: Combined approach to hepatocellular carcinoma: A new treatment concept for nonresectable disease. Expert Rev Anticancer Ther. 8:1743–1749. 2008. View Article : Google Scholar : PubMed/NCBI
17	Dong Y, Dezhong L, Huiying Z, et al: Primary study of TACE combined with sorafenib in hepatocellular carcinoma. Chin Clin Oncol. 15:359–361. 2010.
18	Li Y, Huang JW, Lu LG, Shao PJ, Hu BS, Huang GM, Wei ZG and Zhang L: Clinical analysis of the treatment: Transcatheter arterial chemoembolization combined with sorafenib in advanced hepatocellular carcinoma. Zhonghua Yi Xue Za Zhi. 90:2187–2192. 2010.(In Chinese). PubMed/NCBI
19	Cabrera R, Pannu DS, Caridi J, et al: The combination of sorafenib with transarterial chemoembolisation for hepatocellular carcinoma. Aliment Pharmacol Ther. 34:205–213. 2011. View Article : Google Scholar : PubMed/NCBI
20	Pawlik TM, Reyes DK, Cosgrove D, Kamel IR, Bhagat N and Geschwind JF: Phase II trial of sorafenib combined with concurrent transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma. J Clin Oncol. 29:3960–3967. 2011. View Article : Google Scholar : PubMed/NCBI
21	Song T, Zhang W, Wu Q, Kong D and Ma W: A single center experience of sorafenib in advanced hepatocellular carcinoma patients: evaluation of prognostic factors. Eur J Gastroenterol Hepatol. 23:1233–1238. 2011. View Article : Google Scholar : PubMed/NCBI
22	Vincenzi B, Santini D, Russo A, et al: Early skin toxicity as a predictive factor for tumor control in hepatocellular carcinoma patients treated with sorafenib. Oncologist. 15:85–92. 2010. View Article : Google Scholar : PubMed/NCBI
23	Otsuka T, Eguchi Y, Kawazoe S, et al: Skin toxicities and survival in advanced hepatocellular carcinoma patients treated with sorafenib. Hepatol Res. 42:879–886. 2012. View Article : Google Scholar : PubMed/NCBI
24	van Malenstein H, Dekervel J, Verslype C, Van Cutsem E, Windmolders P, Nevens F and van Pelt J: Long-term exposure to sorafenib of liver cancer cells induces resistance with epithelial-to-mesenchymal transition, increased invasion and risk of rebound growth. Cancer Lett. 329:74–83. 2013. View Article : Google Scholar : PubMed/NCBI