Effect and safety of sorafenib in patients with intermediate hepatocellular carcinoma who received transarterial chemoembolization: A retrospective comparative study

Xue-Fen Lei, Yang Ke, Tian-Hao Bao, Hao-Ran Tang, Xue-Song Wu, Zhi-Tian Shi, Jie Lin, Zhi-Xian Zhang, Hou Gu, Lin Wang, Xue-Fen Lei, Yang Ke, Tian-Hao Bao, Hao-Ran Tang, Xue-Song Wu, Zhi-Tian Shi, Jie Lin, Zhi-Xian Zhang, Hou Gu, Lin Wang

Abstract

Aim: To evaluate the safety and efficacy of sorafenib plus transarterial chemoembolization (TACE) treatment for intermediate hepatocellular carcinoma (HCC).

Methods: Sixty-seven patients with intermediate-stage [Barcelona Clinic liver cancer stage B (BCLC-B)] HCC who were treated with sorafenib plus TACE or TACE alone between 2009 and 2011 were included in the study. Follow-up was until 2014 or patient death. Two groups were defined in the experiment: The experimental group, treated with sorafenib plus TACE, and the control group, treated with standard TACE alone.

Results: The Kaplan-Meier survival analysis showed that the median overall survival (mOS) of the experimental group was 35.2 mo, while that of the control group was 22.0 mo (P < 0.05). Sorafenib plus TACE showed higher incidence rates of rash, hand-foot syndrome (HFS), and hypertension (P < 0.05) than TACE treatment alone.

Conclusion: Sorafenib plus TACE treatment for BCLC-B HCC significantly prolonged the mOS of patients compared to TACE treatment alone. The most common toxicities with sorafenib were rash (31.6%), HFS (39.5%) and hypertension (31.6%), but there were no intolerable adverse events. The Cox multivariate analysis showed that the survival of patients with BCLC-B HCC depended on the Child-Pugh classification, tumor diameter, and treatment with sorafenib plus TACE compared to TACE alone.

Keywords: Adverse reaction; Hepatocellular carcinoma; Overall survival; Sorafenib; Transarterial chemoembolization.

Conflict of interest statement

Conflict-of-interest statement: The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Kaplan-Meier survival cure for the sorafenib plus transarterial chemoembolization and the transarterial chemoembolization alone group.

References

    1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.
    1. Sun Y, Wang Y, Li M, Cheng K, Zhao X, Zheng Y, Liu Y, Lei S, Wang L. Long-term trends of liver cancer mortality by gender in urban and rural areas in China: an age-period-cohort analysis. BMJ Open. 2018;8:e020490.
    1. Ye JZ, Chen JZ, Li ZH, Bai T, Chen J, Zhu SL, Li LQ, Wu FX. Efficacy of postoperative adjuvant transcatheter arterial chemoembolization in hepatocellular carcinoma patients with microvascular invasion. World J Gastroenterol. 2017;23:7415–7424.
    1. Gomaa AI, Waked I. Recent advances in multidisciplinary management of hepatocellular carcinoma. World J Hepatol. 2015;7:673–687.
    1. Harding JJ, Abou-Alfa GK. Systemic therapy for hepatocellular carcinoma. China Clinical Oncol. 2013;2:37.
    1. Bruix J, Sherman M; American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020–1022.
    1. Qu XD, Chen CS, Wang JH, Yan ZP, Chen JM, Gong GQ, Liu QX, Luo JJ, Liu LX, Liu R, et al. The efficacy of TACE combined sorafenib in advanced stages hepatocellullar carcinoma. BMC Cancer. 2012;12:263.
    1. Arizumi T, Ueshima K, Minami T, Kono M, Chishina H, Takita M, Kitai S, Inoue T, Yada N, Hagiwara S, et al. Effectiveness of Sorafenib in Patients with Transcatheter Arterial Chemoembolization (TACE) Refractory and Intermediate-Stage Hepatocellular Carcinoma. Liver Cancer. 2015;4:253–262.
    1. Inghilesi AL, Gallori D, Antonuzzo L, Forte P, Tomcikova D, Arena U, Colagrande S, Pradella S, Fani B, Gianni E, et al. Predictors of survival in patients with established cirrhosis and hepatocellular carcinoma treated with sorafenib. World J Gastroenterol. 2014;20:786–794.
    1. Nojiri K, Sugimoto K, Shiraki K, Tameda M, Inagaki Y, Ogura S, Kasai C, Kusagawa S, Yoneda M, Yamamoto N, et al. Sorafenib and TRAIL have synergistic effect on hepatocellular carcinoma. Int J Oncol. 2013;42:101–108.
    1. Nakano M, Tanaka M, Kuromatsu R, Nagamatsu H, Tajiri N, Satani M, Niizeki T, Aino H, Okamura S, Iwamoto H, et al. Sorafenib for the treatment of advanced hepatocellular carcinoma with extrahepatic metastasis: a prospective multicenter cohort study. Cancer Med. 2015;4:1836–1843.
    1. van Malenstein H, Maleux G, Vandecaveye V, Heye S, Laleman W, van Pelt J, Vaninbroukx J, Nevens F, Verslype C. A randomized phase II study of drug-eluting beads versus transarterial chemoembolization for unresectable hepatocellular carcinoma. Onkologie. 2011;34:368–376.
    1. Ang C, O’Reilly EM, Abou-Alfa GK. Targeted agents and systemic therapy in hepatocellular carcinoma. Recent Results Cancer Res. 2013;190:225–246.
    1. Xie B, Wang DH, Spechler SJ. Sorafenib for treatment of hepatocellular carcinoma: a systematic review. Dig Dis Sci. 2012;57:1122–1129.
    1. Dhir M, Melin AA, Douaiher J, Lin C, Zhen WK, Hussain SM, Geschwind JF, Doyle MB, Abou-Alfa GK, Are C. A Review and Update of Treatment Options and Controversies in the Management of Hepatocellular Carcinoma. Ann Surg. 2016;263:1112–1125.
    1. Abou-Alfa GK. Approaching the era of personalised therapy for liver cancer? Lancet Oncol. 2013;14:7–8.
    1. Yoo JJ, Lee JH, Lee SH, Lee M, Lee DH, Cho Y, Lee YB, Yu SJ, Kim HC, Kim YJ, et al. Comparison of the effects of transarterial chemoembolization for advanced hepatocellular carcinoma between patients with and without extrahepatic metastases. PLoS One. 2014;9:e113926.
    1. Liu C, Sun L, Xu J, Zhao Y. Clinical efficacy of postoperative adjuvant transcatheter arterial chemoembolization on hepatocellular carcinoma. World J Surg Oncol. 2016;14:100.
    1. Zhang ZH, Liu QX, Zhang W, Ma JQ, Wang JH, Luo JJ, Liu LX, Yan ZP. Combined endovascular brachytherapy, sorafenib, and transarterial chemobolization therapy for hepatocellular carcinoma patients with portal vein tumor thrombus. World J Gastroenterol. 2017;23:7735–7745.
    1. Wang W, Bai W, Wang E, Zhao Y, Liu L, Yang M, Cai H, Xia D, Zhang L, Niu J, et al. mRECIST response combined with sorafenib-related adverse events is superior to either criterion alone in predicting survival in HCC patients treated with TACE plus sorafenib. Int J Cancer. 2017;140:390–399.
    1. Cui HZ, Dai GH, Shi Y, Chen L. Sorafenib combined with TACE in advanced primary hepatocellular carcinoma. Hepatogastroenterology. 2013;60:305–310.
    1. Keating GM, Santoro A. Sorafenib: a review of its use in advanced hepatocellular carcinoma. Drugs. 2009;69:223–240.
    1. Marrero JA, Kudo M, Venook AP, Ye SL, Bronowicki JP, Chen XP, Dagher L, Furuse J, Geschwind JH, de Guevara LL, et al. Observational registry of sorafenib use in clinical practice across Child-Pugh subgroups: The GIDEON study. J Hepatol. 2016;65:1140–1147.
    1. Al-Rajabi R, Patel S, Ketchum NS, Jaime NA, Lu TW, Pollock BH, Mahalingam D. Comparative dosing and efficacy of sorafenib in hepatocellular cancer patients with varying liver dysfunction. J Gastrointest Oncol. 2015;6:259–267.
    1. Gadaleta CD, Ranieri G. Trans-arterial chemoembolization as a therapy for liver tumours: New clinical developments and suggestions for combination with angiogenesis inhibitors. Crit Rev Oncol Hematol. 2011;80:40–53.
    1. Guan YS, He Q, Wang MQ. Transcatheter arterial chemoembolization: history for more than 30 years. ISRN Gastroenterol. 2012;2012:480650.
    1. Zhao Y, Wang WJ, Guan S, Li HL, Xu RC, Wu JB, Liu JS, Li HP, Bai W, Yin ZX, 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.
    1. Moschouris H, Malagari K, Papadaki MG, Kornezos I, Stamatiou K, Anagnostopoulos A, Chatzimichael K, Kelekis N. mRECIST criteria and contrast-enhanced US for the assessment of the response of hepatocellular carcinoma to transarterial chemoembolization. Diagn Interv Radiol. 2014;20:136–142.
    1. Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30:52–60.
    1. Federico A, Orditura M, Cotticelli G, DE Sio I, Romano M, Gravina AG, Dallio M, Fabozzi A, Ciardiello F, Loguercio C, et al. Safety and efficacy of sorafenib in patients with advanced hepatocellular carcinoma and Child-Pugh A or B cirrhosis. Oncol Lett. 2015;9:1628–1632.
    1. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–390.
    1. El-Serag HB, Margaret M, Alkek AB. Current Status of Sorafenib Use for Treatment of Hepatocellular Carcinoma. Gastroenterol Hepatol (NY) 2017;13:623–625.
    1. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, 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.
    1. Arizumi T, Ueshima K, Chishina H, Kono M, Takita M, Kitai S, Inoue T, Yada N, Hagiwara S, Minami Y, et al. Duration of stable disease is associated with overall survival in patients with advanced hepatocellular carcinoma treated with sorafenib. Dig Dis. 2014;32:705–710.
    1. van Malenstein H, Dekervel J, Verslype C, Van Cutsem E, Windmolders P, Nevens F, 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. 2013;329:74–83.
    1. Ebos JM, Lee CR, Cruz-Munoz W, Bjarnason GA, Christensen JG, Kerbel RS. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell. 2009;15:232–239.
    1. Pàez-Ribes M, Allen E, Hudock J, Takeda T, Okuyama H, Viñals F, Inoue M, Bergers G, Hanahan D, Casanovas O. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell. 2009;15:220–231.
    1. Cabrera R, Pannu DS, Caridi J, Firpi RJ, Soldevila-Pico C, Morelli G, Clark V, Suman A, George TJ Jr, Nelson DR. The combination of sorafenib with transarterial chemoembolisation for hepatocellular carcinoma. Aliment Pharmacol Ther. 2011;34:205–213.
    1. Sansonno D, Lauletta G, Russi S, Conteduca V, Sansonno L, Dammacco F. Transarterial chemoembolization plus sorafenib: a sequential therapeutic scheme for HCV-related intermediate-stage hepatocellular carcinoma: a randomized clinical trial. Oncologist. 2012;17:359–366.
    1. Luo J, Guo RP, Lai EC, Zhang YJ, Lau WY, Chen MS, Shi M. Transarterial chemoembolization for unresectable hepatocellular carcinoma with portal vein tumor thrombosis: a prospective comparative study. Ann Surg Oncol. 2011;18:413–420.
    1. Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT, Fan ST, Wong J. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002;35:1164–1171.
    1. Huang M, Wang L, Chen J, Bai M, Zhou C, Liu S, Lin Q. Regulation of COX-2 expression and epithelial-to-mesenchymal transition by hypoxia-inducible factor-1α is associated with poor prognosis in hepatocellular carcinoma patients post TACE surgery. Int J Oncol. 2016;48:2144–2154.
    1. Kim HC, Lee JH, Chung JW, Kang B, Yoon JH, Kim YJ, Lee HS, Jae HJ, Park JH. Transarterial chemoembolization with additional cisplatin infusion for hepatocellular carcinoma invading the hepatic vein. J Vasc Interv Radiol. 2013;24:274–283.
    1. Sergio A, Cristofori C, Cardin R, Pivetta G, Ragazzi R, Baldan A, Girardi L, Cillo U, Burra P, Giacomin A, et al. Transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): the role of angiogenesis and invasiveness. Am J Gastroenterol. 2008;103:914–921.
    1. Shim JH, Park JW, Kim JH, An M, Kong SY, Nam BH, Choi JI, Kim HB, Lee WJ, Kim CM. Association between increment of serum VEGF level and prognosis after transcatheter arterial chemoembolization in hepatocellular carcinoma patients. Cancer Sci. 2008;99:2037–2044.
    1. Choi GH, Shim JH, Kim MJ, Ryu MH, Ryoo BY, Kang YK, Shin YM, Kim KM, Lim YS, Lee HC. Sorafenib alone versus sorafenib combined with transarterial chemoembolization for advanced-stage hepatocellular carcinoma: results of propensity score analyses. Radiology. 2013;269:603–611.
    1. Park JW, Koh YH, Kim HB, Kim HY, An S, Choi JI, Woo SM, Nam BH. Phase II study of concurrent transarterial chemoembolization and sorafenib in patients with unresectable hepatocellular carcinoma. J Hepatol. 2012;56:1336–1342.
    1. Zhang X, Wang K, Wang M, Yang G, Ye X, Wu M, Cheng S. Transarterial chemoembolization (TACE) combined with sorafenib versus TACE for hepatocellular carcinoma with portal vein tumor thrombus: a systematic review and meta-analysis. Oncotarget. 2017;8:29416–29427.
    1. Buczak K, Ori A, Kirkpatrick JM, Holzer K, Dauch D, Roessler S, Endris V, Lasitschka F, Parca L, Schmidt A, et al. Spatial Tissue Proteomics Quantifies Inter- and Intratumor Heterogeneity in Hepatocellular Carcinoma (HCC) Mol Cell Proteomics. 2018;17:810–825.
    1. Berk V, Kaplan MA, Tonyali O, Buyukberber S, Balakan O, Ozkan M, Demirci U, Ozturk T, Bilici A, Tastekin D, et al. Efficiency and side effects of sorafenib therapy for advanced hepatocellular carcinoma: a retrospective study by the anatolian society of medical oncology. Asian Pac J Cancer Prev. 2013;14:7367–7369.
    1. Abou-Alfa GK. Sorafenib use in hepatocellular carcinoma: more questions than answers. Hepatology. 2014;60:15–18.
    1. Kudo M, Imanaka K, Chida N, Nakachi K, Tak WY, Takayama T, Yoon JH, Hori T, Kumada H, Hayashi N, et al. Phase III study of sorafenib after transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular carcinoma. Eur J Cancer. 2011;47:2117–2127.

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