Bi-monthly hepatic arterial infusion chemotherapy as a novel strategy for advanced hepatocellular carcinoma in decompensated cirrhotic patients

다국어 초록 (Multilingual Abstract)

Background/Aims: We previously reported the comparable efficacy of bi-monthly hepatic arterial infusion chemotherapy (B-HAIC) to that of sorafenib chemotherapy for the treatment of advanced hepatocellular carcinoma (aHCC) in patients with compensated cirrhosis. In this study, we demonstrate the efficacy of B-HAIC in patients with decompensated cirrhosis.
Methods: Forty-five patients with aHCC refractory to transcatheter arterial chemo-embolization (TACE) were treated with B-HAIC and were divided into two groups according to hepatic functional reserve (Child-Pugh grade). Overall survival period, treatment response, and adverse events in each group were analyzed.
Results: Efficacy and disease control rates in the Child-Pugh B group (n=24; 21% and 71%, respectively) were not significantly impaired compared the Child-Pugh A group (n=21; 38% and 67%, respectively). Median survival time and survival rate at 12 months in the Child-Pugh B group were 422 days and 58.3%, respectively, whereas those in the Child- Pugh A group were 567 days and 70.8%, respectively. Importantly, the hepatic functional reserve of patients did not worsen in either group during the treatment period. Furthermore, the occurrence rate of adverse events leading to discontinuation of anti-tumor treatment was not significantly increased in the Child-Pugh B group.
Conclusions: Given the preservation of hepatic functional reserve afforded by B-HAIC chemotherapy in patients with decompensated cirrhosis, B-HAIC might be an acceptable alternative strategy for aHCC patients who do not respond to TACE.

참고문헌 (Reference)

1 Park SJ, "Usefulness of AFP, AFP-L3, and PIVKA-II, and their combinations in diagnosing hepatocellular carcinoma" 96 : e5811-, 2017

2 Pugh RN, "Transection of the oesophagus for bleeding oesophageal varices" 60 : 646-649, 1973

3 Iwasa S, "Transcatheter arterial infusion chemotherapy with a fine-powder formulation of cisplatin for advanced hepatocellular carcinoma refractory to transcatheter arterial chemoembolization" 41 : 770-775, 2011

4 Cammà C, "Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials" 224 : 47-54, 2002

5 Llovet JM, "Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival" 37 : 429-442, 2003

6 Llovet JM, "Sorafenib in advanced hepatocellular carcinoma" 359 : 378-390, 2008

7 Swift B, "Sorafenib hepatobiliary disposition: mechanism of hepatic uptake and disposition of generated metabolites" 41 : 1179-1186, 2013

8 Niizeki T, "Serum vascular endothelial growth factor as a predictor of response and survival in patients with advanced hepatocellular carcinoma undergoing hepatic arterial infusion chemotherapy" 47 : 686-695, 2012

9 Lo CM, "Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma" 35 : 1164-1171, 2002

10 Yoshikawa M, "Phase II study of hepatic arterial infusion of a fine-powder formulation of cisplatin for advanced hepatocellular carcinoma" 38 : 474-483, 2008

11 Lencioni R, "Modified RECIST (mRECIST) assessment for hepatocellular carcinoma" 30 : 52-60, 2010

12 Kudo M, "Management of hepatocellular carcinoma in Japan: Consensus-Based Clinical Practice Guidelines proposed by the Japan Society of Hepatology (JSH) 2010 updated version" 29 : 339-364, 2011

13 Kudo M, "Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomized phase 3 non-inferiority trial" 391 : 1163-1173, 2018

14 Kudo M, "JSH consensus-based clinical practice guideline for the management of hepatocellular carcinoma: 2014 update by the Liver Cancer Study Group of Japan" 3 : 458-468, 2014

15 Tsai WL, "Hepatic arterial infusion chemotherapy for patients with huge unresectable hepatocellular carcinoma" 9 : e92784-, 2014

16 Miyaki D, "Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma according to Child-Pugh classification" 27 : 1850-1857, 2012

17 Lin DY, "Hepatic arterial embolization in patients with unresectable hepatocellular carcinoma--a randomized controlled trial" 94 : 453-456, 1998

18 Kaneko S, "Guideline on the use of new anticancer drugs for the treatment of Hepatocellular Carcinoma 2010 update" 42 : 523-542, 2012

19 Terashima T, "Feasibility and efficacy of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma after sorafenib" 44 : 1179-1185, 2014

20 Fukubayashi K, "Evaluation of sorafenib treatment and hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma: a comparative study using the propensity score matching method" 4 : 1214-1223, 2015

21 Ministry of Health, Labour and Welfare, "Ethical Guidelines for Medical and Health Research Involving Human Subjects" Ministry of Health, Labour and Welfare

22 Ikeda M, "Efficacy of sorafenib in patients with hepatocellular carcinoma refractory to trasncatheter arterial chemoembolization" 49 : 932-940, 2014

23 Moriya K, "Efficacy of bi-monthly hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma" 4 : 741-749, 2018

24 오명진, "Efficacy and safety of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma as firstline therapy" 대한간학회 19 (19): 288-299, 2013

25 Lok AS, "Des-gamma-carboxy prothrombin and alpha-fetoprotein as biomarkers for the early detection of hepatocellular carcinoma" 138 : 493-502, 2010

26 Ishikawa T, "Concurrent partial splenic embolization with transcatheter arterial chemoembolization for hepatocellular carcinoma can maintain hepatic functional reserve" 44 : 1056-1061, 2014

27 Hatooka M, "Comparison of outcome of hepatic arterial infusion chemotherapy and sorafenib in patients with hepatocellular carcinoma refractory to transcatheter arterial chemoembolization" 36 : 3523-3529, 2016

28 Kawaoka T, "Comparison of hepatic arterial infusion chemotherapy versus sorafenib monotherapy in patients with advanced hepatocellular carcinoma" 16 : 505-512, 2015

29 National Cancer Institute, "Common Terminology Criteria for Adverse Events" National Institutes of Health

30 Montano-Loza AJ, "Clinical relevance of sarcopenia in patients with cirrhosis" 20 : 8061-8071, 2014

31 Hussein Z, "Clinical pharmacokinetic and pharmacodynamic profile of lenvatinib, an orally active, small module, multitargeted tyrosine kinase inhibitor" 42 : 903-914, 2017

32 World Health Organization, "Cancer Today" WHO

33 Nishikawa H, "Branched-chain amino acid treatment before transcatheter arterial chemoembolization for hepatocellular carcinoma" 18 : 1379-1384, 2012

34 Llovet JM, "Arterial embolization or chemoembolization versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomized controlled trial" 359 : 1734-1739, 2002

35 Heimbach JK, "AASLD guidelines for the treatment of hepatocellular carcinoma" 67 : 358-380, 2018

36 Shao YY, "A pilot study of hepatic arterial infusion of chemotherapy for patients with advanced hepatocellular carcinoma who have failed antiangiogenic therapy" 33 : 1413-1419, 2013

37 Groupe d’Etude et de Traitement du Carcinome Hépatocellulaire, "A comparison of lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma" 332 : 1256-1261, 1995

38 Lu W, "A comparative study of damage to liver function after TACE with use of low-dose versus conventional-dose of anticancer drugs in hepatocellular carcinoma" 54 : 1499-1502, 2007

39 Song DS, "A comparative study between sorafenib and hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis" 50 : 445-454, 2015