Efficacy and safety of hepatic arterial infusion chemotherapy<i> versus</i> sorafenib in advanced hepatocellular carcinoma: a systematic review_Chinese Journal of Evidence-Based Medicine

Authors：

JIANG Ni ¹ , ZHONG Pengyu ² , LI Min ¹ , LI Junfeng ¹ , MAO Yongwu ¹ , CHEN Lin ¹ ,  MAO Xiaorong ¹

1. Department of Infectious Diseases, First Hospital of Lanzhou University, Lanzhou 730000, P. R. China;
2. The First Clinical Medical College of Lanzhou University, Lanzhou 730000, P. R. China;

Corresponding author：

MAO Xiaorong, Email: mxr2013@126.com

Keywords：

Hepatocellular carcinoma; Hepatic arterial infusion chemotherapy; Sorafenib; Meta-analysis; Systematic review

DOI：

10.7507/1672-2531.202112110

Video：

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Objective To systematically review the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) and sorafenib (SORF) separately or combined in the treatment of advanced hepatocellular carcinoma (HCC). Methods We searched the PubMed, EMbase, The Cochrane Library, CNKI, WanFang Data and VIP databases for studies on HAIC and SORA separately or in combination in the treatment of advanced HCC from inception to November 1, 2021. Two reviewers independently screened the literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed using RevMan 5.3 software. Results A total of 21 studies involving 2 501 patients were included. The results of meta-analysis showed that the overall survival (OS) (HR=0.46, 95% CI 0.25 to 0.87, P=0.02), objective response rate (ORR) (OR=4.00, 95%CI 2.74 to 5.85, P<0.000 01) and disease control rate (DCR) (OR=2.20, 95%CI 1.30 to 3.75, P=0.004) were higher in the HAIC group than the SORF group, while the incidence of adverse reactions was not increased. However, HAIC combined with SORF showed no significant difference in OS, ORR, DCR or progression-free survival (PFS) compared with SORF alone. Moreover, combined treatment increased the adverse reactions of blood system. Conclusion The current study suggests that HAIC can improve OS, ORR and DCR in patients with advanced HCC; however, there is no additional benefit when combining SORF with HAIC. Due to the limited quantity and quality of the included studies, more high-quality studies are needed to verify the above conclusion.

Citation： JIANG Ni, ZHONG Pengyu, LI Min, LI Junfeng, MAO Yongwu, CHEN Lin, MAO Xiaorong. Efficacy and safety of hepatic arterial infusion chemotherapy versus sorafenib in advanced hepatocellular carcinoma: a systematic review. Chinese Journal of Evidence-Based Medicine, 2022, 22(8): 901-907. doi: 10.7507/1672-2531.202112110 Copy

1.	Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer, 2015, 136(5): E359-E386.
2.	Rich N, Singal AG. Hepatocellular carcinoma tumour markers: current role and expectations. Best Pract Res Clin Gastroenterol, 2014, 28(5): 843-853.
3.	Li S, Xu J, Zhang H, et al. The role of hepatic arterial infusion chemotherapy in the treatment of hepatocellular carcinoma: a systematic review and meta-analysis. Chemotherapy, 2021, 66(4): 124-133.
4.	Song MJ. Hepatic artery infusion chemotherapy for advanced hepatocellular carcinoma. World J Gastroenterol, 2015, 21(13): 3843-3849.
5.	Ikeda M, Mitsunaga S, Shimizu S, et al. Efficacy of sorafenib in patients with hepatocellular carcinoma refractory to transcatheter arterial chemoembolization. J Gastroenterol, 2014, 49(5): 932-940.
6.	Kang MK, Park JG, Lee HJ. Comparison of clinical outcomes between sorafenib and hepatic artery infusion chemotherapy in advanced hepatocellular carcinoma: a STROBE-compliant article. Medicine (Baltimore), 2018, 97(17): e0611.
7.	Lyu N, Kong Y, Mu L, et al. Hepatic arterial infusion of oxaliplatin plus fluorouracil/leucovorin vs. sorafenib for advanced hepatocellular carcinoma. J Hepatol, 2018, 69(1): 60-69.
8.	Moriguchi M, Aramaki T, Nishiofuku H, et al. Sorafenib versus hepatic arterial infusion chemotherapy as initial treatment for hepatocellular carcinoma with advanced portal vein tumor thrombosis. Liver Cancer, 2017, 6(4): 275-286.
9.	Moriya K, Namisaki T, Sato S, et al. Efficacy of bi-monthly hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma. J Gastrointest Oncol, 2018, 9(4): 741-749.
10.	Song DS, Song MJ, Bae SH, et al. A comparative study between sorafenib and hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis. J Gastroenterol, 2015, 50(4): 445-454.
11.	Hiramine Y, Uto H, Imamura Y, et al. Sorafenib and hepatic arterial infusion chemotherapy for unresectable advanced hepatocellular carcinoma: a comparative study. Exp Ther Med, 2011, 2(3): 433-441.
12.	Yang H, Woo HY, Lee SK, et al. A comparative study of sorafenib and metronomic chemotherapy for Barcelona clinic liver cancer-stage C hepatocellular carcinoma with poor liver function. Clin Mol Hepatol, 2017, 23(2): 128-137.
13.	Choi JH, Chung WJ, Bae SH, et al. Randomized, prospective, comparative study on the effects and safety of sorafenib vs. hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma with portal vein tumor thrombosis. Cancer Chemother Pharmacol, 2018, 82(3): 469-478.
14.	Ahn YE, Suh SJ, Yim HJ, et al. Comparison of sorafenib versus hepatic arterial infusion chemotherapy-based treatment for advanced hepatocellular carcinoma with portal vein tumor thrombosis. Gut Liver, 2021, 15(2): 284-294.
15.	Jeong SW, Jang JY, Lee JE, et al. The efficacy of hepatic arterial infusion chemotherapy as an alternative to sorafenib in advanced hepatocellular carcinoma. Asia Pac J Clin Oncol, 2012, 8(2): 164-171.
16.	Fukubayashi K, Tanaka M, Izumi K, et al. Evaluation of sorafenib treatment and hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma: a comparative study using the propensity score matching method. Cancer Med, 2015, 4(8): 1214-1223.
17.	Nakano M, Niizeki T, Nagamatsu H, et al. Clinical effects and safety of intra-arterial infusion therapy of cisplatin suspension in lipiodol combined with 5-fluorouracil versus sorafenib, for advanced hepatocellular carcinoma with macroscopic vascular invasion without extra-hepatic spread: a prospective cohort study. Mol Clin Oncol, 2017, 7(6): 1013-1020.
18.	Hatooka M, Kawaoka T, Aikata H, et al. Comparison of outcome of hepatic arterial infusion chemotherapy and sorafenib in patients with hepatocellular carcinoma refractory to transcatheter arterial chemoembolization. Anticancer Res, 2016, 36(7): 3523-3530.
19.	Kawaoka T, Aikata H, Hyogo H, et al. Comparison of hepatic arterial infusion chemotherapy versus sorafenib monotherapy in patients with advanced hepatocellular carcinoma. J Dig Dis, 2015, 16(9): 505-512.
20.	Kondo M, Morimoto M, Ishii T, et al. Hepatic arterial infusion chemotherapy with cisplatin and sorafenib in hepatocellular carcinoma patients unresponsive to transarterial chemoembolization: a propensity score-based weighting. J Dig Dis, 2015, 16(3): 143-151.
21.	Kondo M, Morimoto M, Kobayashi S, et al. Randomized, phase Ⅱ trial of sequential hepatic arterial infusion chemotherapy and sorafenib versus sorafenib alone as initial therapy for advanced hepatocellular carcinoma: SCOOP-2 trial. BMC Cancer, 2019, 19(1): 954.
22.	Kudo M, Ueshima K, Yokosuka O, et al. Sorafenib plus low-dose cisplatin and fluorouracil hepatic arterial infusion chemotherapy versus sorafenib alone in patients with advanced hepatocellular carcinoma (SILIUS): a randomised, open label, phase 3 trial. Lancet Gastroenterol Hepatol, 2018, 3(6): 424-432.
23.	He M, Li Q, Zou R, et al. Sorafenib plus hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin vs sorafenib alone for hepatocellular carcinoma with portal vein invasion: a randomized clinical trial. JAMA Oncol, 2019, 5(7): 953-960.
24.	Ikeda M, Shimizu S, Sato T, et al. Sorafenib plus hepatic arterial infusion chemotherapy with cisplatin versus sorafenib for advanced hepatocellular carcinoma: randomized phase Ⅱ trial. Ann Oncol, 2016, 27(11): 2090-2096.
25.	Ikuta S, Aihara T, Yamanaka N. Efficacy of sequential sorafenib plus hepatic arterial infusion chemotherapy in patients with Barcelona clinic liver cancer stage B and C hepatocellular carcinoma: a retrospective single-institution study. Contemp Oncol (Pozn), 2018, 22(3): 165-171.
26.	Akiyama M, Miyaaki H, Miuma S, et al. Significance of trans-hepatic arterial chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombus. Oncol Rep, 2008, 20(2): 353-357.
27.	Gatti L, Cassinelli G, Zaffaroni N, et al. New mechanisms for old drugs: Insights into DNA-unrelated effects of platinum compounds and drug resistance determinants. Drug Resist Updat, 2015, 20: 1-11.
28.	Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol, 2014, 740: 364-378.
29.	Wigmore PM, Mustafa S, El-Beltagy M, et al. Effects of 5-FU. Adv Exp Med Biol, 2010, 678: 157-164.
30.	Hato SV, Khong A, de Vries IJ, et al. Molecular pathways: the immunogenic effects of platinum-based chemotherapeutics. Clin Cancer Res, 2014, 20(11): 2831-2837.
31.	Ouyang G, Pan G, Xu H, et al. Sorafenib plus hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma: a systematic review and meta-analysis. J Clin Gastroenterol, 2020, 54(8): 675-681.
32.	Zhang W, Wang X, Huang R, et al. Prognostic value of marital status on stage at diagnosis in hepatocellular carcinoma. Sci Rep, 2017, 7: 41695.

1. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer, 2015, 136(5): E359-E386.
2. Rich N, Singal AG. Hepatocellular carcinoma tumour markers: current role and expectations. Best Pract Res Clin Gastroenterol, 2014, 28(5): 843-853.
3. Li S, Xu J, Zhang H, et al. The role of hepatic arterial infusion chemotherapy in the treatment of hepatocellular carcinoma: a systematic review and meta-analysis. Chemotherapy, 2021, 66(4): 124-133.
4. Song MJ. Hepatic artery infusion chemotherapy for advanced hepatocellular carcinoma. World J Gastroenterol, 2015, 21(13): 3843-3849.
5. Ikeda M, Mitsunaga S, Shimizu S, et al. Efficacy of sorafenib in patients with hepatocellular carcinoma refractory to transcatheter arterial chemoembolization. J Gastroenterol, 2014, 49(5): 932-940.
6. Kang MK, Park JG, Lee HJ. Comparison of clinical outcomes between sorafenib and hepatic artery infusion chemotherapy in advanced hepatocellular carcinoma: a STROBE-compliant article. Medicine (Baltimore), 2018, 97(17): e0611.
7. Lyu N, Kong Y, Mu L, et al. Hepatic arterial infusion of oxaliplatin plus fluorouracil/leucovorin vs. sorafenib for advanced hepatocellular carcinoma. J Hepatol, 2018, 69(1): 60-69.
8. Moriguchi M, Aramaki T, Nishiofuku H, et al. Sorafenib versus hepatic arterial infusion chemotherapy as initial treatment for hepatocellular carcinoma with advanced portal vein tumor thrombosis. Liver Cancer, 2017, 6(4): 275-286.
9. Moriya K, Namisaki T, Sato S, et al. Efficacy of bi-monthly hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma. J Gastrointest Oncol, 2018, 9(4): 741-749.
10. Song DS, Song MJ, Bae SH, et al. A comparative study between sorafenib and hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis. J Gastroenterol, 2015, 50(4): 445-454.
11. Hiramine Y, Uto H, Imamura Y, et al. Sorafenib and hepatic arterial infusion chemotherapy for unresectable advanced hepatocellular carcinoma: a comparative study. Exp Ther Med, 2011, 2(3): 433-441.
12. Yang H, Woo HY, Lee SK, et al. A comparative study of sorafenib and metronomic chemotherapy for Barcelona clinic liver cancer-stage C hepatocellular carcinoma with poor liver function. Clin Mol Hepatol, 2017, 23(2): 128-137.
13. Choi JH, Chung WJ, Bae SH, et al. Randomized, prospective, comparative study on the effects and safety of sorafenib vs. hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma with portal vein tumor thrombosis. Cancer Chemother Pharmacol, 2018, 82(3): 469-478.
14. Ahn YE, Suh SJ, Yim HJ, et al. Comparison of sorafenib versus hepatic arterial infusion chemotherapy-based treatment for advanced hepatocellular carcinoma with portal vein tumor thrombosis. Gut Liver, 2021, 15(2): 284-294.
15. Jeong SW, Jang JY, Lee JE, et al. The efficacy of hepatic arterial infusion chemotherapy as an alternative to sorafenib in advanced hepatocellular carcinoma. Asia Pac J Clin Oncol, 2012, 8(2): 164-171.
16. Fukubayashi K, Tanaka M, Izumi K, et al. Evaluation of sorafenib treatment and hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma: a comparative study using the propensity score matching method. Cancer Med, 2015, 4(8): 1214-1223.
17. Nakano M, Niizeki T, Nagamatsu H, et al. Clinical effects and safety of intra-arterial infusion therapy of cisplatin suspension in lipiodol combined with 5-fluorouracil versus sorafenib, for advanced hepatocellular carcinoma with macroscopic vascular invasion without extra-hepatic spread: a prospective cohort study. Mol Clin Oncol, 2017, 7(6): 1013-1020.
18. Hatooka M, Kawaoka T, Aikata H, et al. Comparison of outcome of hepatic arterial infusion chemotherapy and sorafenib in patients with hepatocellular carcinoma refractory to transcatheter arterial chemoembolization. Anticancer Res, 2016, 36(7): 3523-3530.
19. Kawaoka T, Aikata H, Hyogo H, et al. Comparison of hepatic arterial infusion chemotherapy versus sorafenib monotherapy in patients with advanced hepatocellular carcinoma. J Dig Dis, 2015, 16(9): 505-512.
20. Kondo M, Morimoto M, Ishii T, et al. Hepatic arterial infusion chemotherapy with cisplatin and sorafenib in hepatocellular carcinoma patients unresponsive to transarterial chemoembolization: a propensity score-based weighting. J Dig Dis, 2015, 16(3): 143-151.
21. Kondo M, Morimoto M, Kobayashi S, et al. Randomized, phase Ⅱ trial of sequential hepatic arterial infusion chemotherapy and sorafenib versus sorafenib alone as initial therapy for advanced hepatocellular carcinoma: SCOOP-2 trial. BMC Cancer, 2019, 19(1): 954.
22. Kudo M, Ueshima K, Yokosuka O, et al. Sorafenib plus low-dose cisplatin and fluorouracil hepatic arterial infusion chemotherapy versus sorafenib alone in patients with advanced hepatocellular carcinoma (SILIUS): a randomised, open label, phase 3 trial. Lancet Gastroenterol Hepatol, 2018, 3(6): 424-432.
23. He M, Li Q, Zou R, et al. Sorafenib plus hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin vs sorafenib alone for hepatocellular carcinoma with portal vein invasion: a randomized clinical trial. JAMA Oncol, 2019, 5(7): 953-960.
24. Ikeda M, Shimizu S, Sato T, et al. Sorafenib plus hepatic arterial infusion chemotherapy with cisplatin versus sorafenib for advanced hepatocellular carcinoma: randomized phase Ⅱ trial. Ann Oncol, 2016, 27(11): 2090-2096.
25. Ikuta S, Aihara T, Yamanaka N. Efficacy of sequential sorafenib plus hepatic arterial infusion chemotherapy in patients with Barcelona clinic liver cancer stage B and C hepatocellular carcinoma: a retrospective single-institution study. Contemp Oncol (Pozn), 2018, 22(3): 165-171.
26. Akiyama M, Miyaaki H, Miuma S, et al. Significance of trans-hepatic arterial chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombus. Oncol Rep, 2008, 20(2): 353-357.
27. Gatti L, Cassinelli G, Zaffaroni N, et al. New mechanisms for old drugs: Insights into DNA-unrelated effects of platinum compounds and drug resistance determinants. Drug Resist Updat, 2015, 20: 1-11.
28. Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol, 2014, 740: 364-378.
29. Wigmore PM, Mustafa S, El-Beltagy M, et al. Effects of 5-FU. Adv Exp Med Biol, 2010, 678: 157-164.
30. Hato SV, Khong A, de Vries IJ, et al. Molecular pathways: the immunogenic effects of platinum-based chemotherapeutics. Clin Cancer Res, 2014, 20(11): 2831-2837.
31. Ouyang G, Pan G, Xu H, et al. Sorafenib plus hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma: a systematic review and meta-analysis. J Clin Gastroenterol, 2020, 54(8): 675-681.
32. Zhang W, Wang X, Huang R, et al. Prognostic value of marital status on stage at diagnosis in hepatocellular carcinoma. Sci Rep, 2017, 7: 41695.

Chinese Journal of Evidence-Based Medicine

Efficacy and safety of hepatic arterial infusion chemotherapy versus sorafenib in advanced hepatocellular carcinoma: a systematic review

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