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CORRESPONDENCE
Year : 2014  |  Volume : 10  |  Issue : 4  |  Page : 1112-1114

Complete remission of hepatocellular carcinoma after transarterial Chemoembolization combined with brivanib


Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China

Date of Web Publication9-Jan-2015

Correspondence Address:
Guohong Han
Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an 710032
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.144564

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 > Abstract 

Transarterial chemoembolization (TACE) has been the standard treatment modality in patients with intermediate stage hepatocellular carcinoma (HCC). Brivanib is an oral small molecular inhibitor of both vascular endothelial growth factor and fibroblast growth factor receptors. Herein, we reported that a 67-year-old patient with intermediate stage HCC achieved the complete remission after TACE combined with brivanib therapy. This finding potentially suggested the benefit of this combination therapy for HCC.

 > Abstract in Chinese 

经导管肝动脉化疗栓塞联合布立尼布治疗肝癌后完全缓解

摘要

肝动脉化疗栓塞(TACE)已成为中期肝癌(HCC)患者的标准治疗方式。布立尼布是口服的血管内皮生长因子和碱性成纤维细胞生长因子双受体的小分子抑制剂。在此,我们报告一例67岁的中期肝癌患者, TACE结合布立尼布治疗后达到完全缓解。这一发现可能提示肝癌的这种联合治疗的益处。

关键词:布立尼布,完全缓解,肝癌,肝动脉化疗栓塞


Keywords: brivanib, complete remission, hepatocellular carcinoma, transarterial chemoembolization


How to cite this article:
Jia J, Qi X, Bai W, Yuan J, Han G. Complete remission of hepatocellular carcinoma after transarterial Chemoembolization combined with brivanib. J Can Res Ther 2014;10:1112-4

How to cite this URL:
Jia J, Qi X, Bai W, Yuan J, Han G. Complete remission of hepatocellular carcinoma after transarterial Chemoembolization combined with brivanib. J Can Res Ther [serial online] 2014 [cited 2019 Nov 23];10:1112-4. Available from: http://www.cancerjournal.net/text.asp?2014/10/4/1112/144564


 > Introduction Top


Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. [1] Notably, 60-70% of patients are not suitable for the curative treatments because HCC is diagnosed at intermediated or advanced stage. Transarterial chemoembolization (TACE) is effective for intermediate stage HCC. [2] However, after TACE, the serum vascular endothelial growth factor (VEGF) and the basic fibroblast growth factor (FGF) are markedly increased, which are significantly associated with poor response to TACE, HCC recurrence and tumor growth. [3] Brivanib is an orally small molecular inhibitor of both VEGF and FGF receptors. [4] A combination of TACE with brivanib has the potential to reduce HCC recurrence and to raise the survival benefit. Herein, we reported a 67-year-old patient with intermediated HCC who achieved the complete remission after this combination therapy.


 > Case report Top


On September 8, 2011, a 67-year-old male patient was admitted to our hospital due to an incidental finding of abnormal mass in the left liver lobe. He had no history of chronic hepatitis B or C virus infection or alcohol abuse. On laboratory tests, alpha-fetoprotein (AFP) was 1086 ng/ml [Figure 1]. Others were normal. Plain computed tomography (CT) found a hypodense parenchyma mass in the left liver lobe; and contrast-enhanced CT showed the arterial phase hypervascularity and venous phase washout of the lesion. The maximum diameter of the entire and viable tumor was 7.9 and 7.9 cm, respectively [Figure 2]. Histological examination showed a well-differentiated HCC. The patient had a Child-Pugh class A, a good performance status of ECOG = 0 and a Barcelona Clinical Liver Cancer stage B.
Figure 1: Change in alpha-fetoprotein level before and after the combined therapy

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Figure 2: Change in contrast-enhanced computed tomography examinations before and after the combined therapy

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On September 21, 2011, a conventional TACE was performed. After that, the AFP level was reduced to 553.9 ng/ml [Figure 1]. However, he developed abnormal liver function, including the alanine transaminase (ALT) 846 U/L (common terminology criteria for adverse events [CTCAE] grade 3), aspartate aminotransferase (AST) 126 U/L (CTCAE grade 2) and total bilirubin (TBIL) 2.3 mg/dl (CTCAE grade 2). He also developed the post-embolization syndrome, including fever (38.8°, CTCAE grade 1) and abdominal distension (CTCAE grade 1). Thus, symptomatic treatments were given. At 8 days later, ALT and AST were reduced to 148 U/L and 21 U/L, respectively; TBIL to 1.4 mg/dl. The fever the abdominal discomfort disappeared. Since then, he started taking brivanib 800 mg/d.

On 4 th weeks after this combination therapy, the AFP level was reduced to 12.18 ng/ml [Figure 1] and the contrast-enhanced CT showed that the lesion had a good lipiodol deposition and the maximum diameter of entire and viable tumor was 7.9 and 2.2 cm, respectively [Figure 2]. The patient achieved a partial response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria and a stable disease (SD) according to the RECIST criteria. Because the patient developed grade 3 fatigue and hyponatremia, the brivanib was stopped from 7 th to 10 th weeks. On 11 th weeks, the fatigue and hyponatremia were reduced to CTCAE grade 1. Thus, brivanib was resumed and reduced to the dosage of 600 mg/d.

On 12 th weeks, the AFP level was reduced to 2.46 ng/ml [Figure 1]. But owing to grade 3 fatigue, the patient had to discontinue the brivanib again. Although, the tumor still existed in the left lobe, the lipiodol deposited well and the colliquation necrosis developed around the tumor. The maximum diameter of the entire tumor was still 7.6 cm, but the viable tumor disappeared completely [Figure 2]. Thus, the patient achieved a complete response (CR) according to the mRECIST criteria and a SD according to RECIST criteria. On 16 th weeks, the fatigue was reduced to grade 1. Thus, the brivanib 400 mg/d was resumed. CT scans were repeated on 20 th , 28 th and 88 th weeks [Figure 2]. The patient recovered well without any recurrence or metastasis. CR was also maintained.


 > Discussion Top


TACE can cause tumor necrosis and slow tumor progression, thereby improving the survival. [5] Currently, TACE has been recommended as the standard treatment for intermediate stage HCC. [1] However, no complete disappearance was reported in HCC patients treated with TACE. Brivanib alone could achieve an objective response rate of 10-12% and a CR rate of 1% by mRECIST criteria. [6],[7] The initial results of the BRISK-TA clinical trial demonstrated that the rate of objective response was 48.2% and the CR rate was only 22.1% in patients receiving the TACE combined with brivanib. Our case underwent one session of TACE in combination with the brivanib for 92 weeks. During the period of taking brivanib, the patient did not develop any serious adverse events. At 20 weeks after the combined therapy, the patient achieved a CR by RECIST criteria. The entire tumor disappeared completely. Until now, the patient maintained CR and did not develop metastasis or recurrence. Notably, this patient had an intermediate stage HCC without macrovascular invasion and extrahepatic metastasis and a good performance status. In addition, the patient did not have virus hepatitis infection and the biopsy proved that the tumor was well-differentiated. These factors might be associated with better overall survival. [8] In addition, the encapsulated tumor might be related to a better response to TACE therapy. [9] Finally, considering that the presence and grade of drug-related adverse event was associated with the overall survival, [10] our case developed grade 3 fatigue several times which might suggested a better response.


 > Conclusions Top


This was the first case of complete remission of intermediate stage HCC after TACE combined with brivanib treatment, which potentially suggested the benefit of this combination therapy.

 
 > References Top

1.
European Association for the Study of the Liver, European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: Management of hepatocellular carcinoma. J Hepatol 2012;56:908-43.  Back to cited text no. 1
    
2.
Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology 2003;37:429-42.  Back to cited text no. 2
    
3.
Li X, Feng GS, Zheng CS, Zhuo CK, Liu X. 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;10:2878-82.  Back to cited text no. 3
    
4.
Cai ZW, Zhang Y, Borzilleri RM, Qian L, Barbosa S, Wei D, et al. Discovery of brivanib alaninate ((S)-((R)-1-(4-(4-fluoro-2-methyl- 1H-indol-5-yloxy)-5-methylpyrrolo[2,1- f][1,2,4]triazin-6-yloxy) propan-2-yl) 2-aminopropanoate), a novel prodrug of dual vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1 kinase inhibitor (BMS-540215). J Med Chem 2008;51:1976-80.  Back to cited text no. 4
    
5.
Liapi E, Georgiades CC, Hong K, Geschwind JF. Transcatheter arterial chemoembolization: Current technique and future promise. Tech Vasc Interv Radiol 2007;10:2-11.  Back to cited text no. 5
    
6.
Johnson PJ, Qin S, Park JW, Poon RT, Raoul JL, Philip PA, et al. Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: Results from the randomized phase III BRISK-FL study. J Clin Oncol 2013;31:3517-24.  Back to cited text no. 6
    
7.
Llovet JM, Decaens T, Raoul JL, Boucher E, Kudo M, Chang C, et al. Brivanib in patients with advanced hepatocellular carcinoma who were intolerant to sorafenib or for whom sorafenib failed: Results from the randomized phase III BRISK-PS study. J Clin Oncol 2013;31:3509-16.  Back to cited text no. 7
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8.
Witjes CD, Willemssen FE, Verheij J, van der Veer SJ, Hansen BE, Verhoef C, et al. Histological differentiation grade and microvascular invasion of hepatocellular carcinoma predicted by dynamic contrast-enhanced MRI. J Magn Reson Imaging 2012;36:641-7.  Back to cited text no. 8
    
9.
Hsieh MY, Chang WY, Wang LY, Chen SC, Chuang WL, Lu SN, et al. Treatment of hepatocellular carcinoma by transcatheter arterial chemoembolization and analysis of prognostic factors. Cancer Chemother Pharmacol 1992;31 Suppl: S82-5.  Back to cited text no. 9
    
10.
Zhao Y, Yang M, Qi X, Han G, Fan D. Drug-related adverse events may predict efficacy in sorafenib therapy for hepatocellular carcinoma. Hepatology 2012;56:790-1.  Back to cited text no. 10
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