Randomized Controlled Trial
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2020; 26(27): 3975-3988
Published online Jul 21, 2020. doi: 10.3748/wjg.v26.i27.3975
Transarterial chemoembolization with hepatic arterial infusion chemotherapy plus S-1 for hepatocellular carcinoma
Jian-Hai Guo, Shao-Xing Liu, Song Gao, Fu-Xin Kou, Xin Zhang, Di Wu, Xiao-Ting Li, Hui Chen, Xiao-Dong Wang, Peng Liu, Peng-Jun Zhang, Hai-Feng Xu, Guang Cao, Lin-Zhong Zhu, Ren-Jie Yang, Xu Zhu
Jian-Hai Guo, Shao-Xing Liu, Song Gao, Fu-Xin Kou, Xin Zhang, Di Wu, Hui Chen, Xiao-Dong Wang, Peng Liu, Peng-Jun Zhang, Hai-Feng Xu, Guang Cao, Lin-Zhong Zhu, Ren-Jie Yang, Xu Zhu, Department of Interventional Therapy, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China
Xiao-Ting Li, Department of Radiology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China
Author contributions: Guo JH, Liu SX and Gao S contributed equally and were responsible for the study conception and design, study conduction, data analysis and interpretation, and manuscript drafting; Kou FX, Zhang X, Chen H, Wang XD, Liu P, Zhang PJ, Xu HF, Cao G and Zhu LZ were responsible for study conduction and data collection; Wu D and Li XT were responsible for data analysis and interpretation; Yang PJ and Zhu X revised the article for important intellectual content; all authors reviewed and approved the final version to be published.
Supported by Sanofi.
Institutional review board statement: The study was reviewed and approved by the Peking University Cancer Hospital Institutional Review Board.
Clinical trial registration statement: The study was registered at ClinicalTrials.gov. The registration identification number is NCT01997957.
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: Guo JH, Liu SX, Gao S, Kou FX, Zhang X, Chen H, Wang XD, Liu P, Xu HF, Cao G, Zhu LZ, Yang RJ, and Zhu X declare non-financial support from Sanofi, during the conduct of the study. The company provided a proportion of the oxaliplatin used in the study for free. The content of the manuscript is solely the responsibility of the authors and does not represent the views of the funder. The funding sources had no role in the design and conduct of the study, the collection, management, analysis, and interpretation of data, preparation, review, or approval of the manuscript nor the decision to submit the manuscript for publication. Wu D, Li XT, and Zhang PJ declare no potential conflicting interests related to this paper.
Data sharing statement: No additional data are available.
CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Xu Zhu, MD, Chief Doctor, Professor, Department of Interventional Therapy, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing 100142, China. drzhuxu@163.com
Received: March 29, 2020
Peer-review started: March 29, 2020
First decision: April 25, 2020
Revised: May 7, 2020
Accepted: July 4, 2020
Article in press: July 4, 2020
Published online: July 21, 2020
Processing time: 113 Days and 23.5 Hours
Abstract
BACKGROUND

Transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have shown promising local benefits for advanced hepatocellular carcinoma (HCC). S-1, a composite preparation of a 5-fluorouracil prodrug, has proven to be a convenient oral chemotherapeutic agent with definite efficacy against advanced HCC.

AIM

To evaluate the efficacy and safety of TACE followed by HAIC with or without oral S-1 for treating advanced HCC.

METHODS

In this single-center, open-label, prospective, randomized controlled trial, 117 participants with advanced HCC were randomized to receive TACE followed by oxaliplatin-based HAIC either with (TACE/HAIC + S-1, n = 56) or without (TACE/HAIC, n = 61) oral S-1 between December 2013 and September 2017. Two participants were excluded from final analysis for withdrawing consent. The primary endpoint was progression-free survival (PFS) and secondary endpoints included overall survival (OS), objective response rate, disease control rate and safety.

RESULTS

In total, 115 participants (100 males and 15 females; mean age, 57.7 years ± 11.9) were analyzed. The median PFS and OS were 5.0 mo (0.4–58.6 mo) (95% confidence interval (CI): 3.82 to 6.18) vs 4.4 mo (1.1–54.4 mo) (95%CI: 2.54 to 6.26; P = 0.585) and 8.4 mo (0.4–58.6 mo) (95%CI: 6.88 to 9.92) vs 8.3 mo (1.4–54.4 m) (95%CI: 5.71 to 10.96; P = 0.985) in the TACE/HAIC + S-1 and TACE/HAIC groups, respectively. The objective response rate and disease control rate were 30.9% vs 18.4% and 72.7% vs 56.7% in the TACE/HAIC + S-1 and TACE/HAIC groups, respectively. Grade 3/4 adverse events had a similar frequency in both treatment groups.

CONCLUSION

No improvements in tumor response rates, PFS or OS were observed with the addition of S-1 to TACE/HAIC in advanced HCC. Both treatment regimens had a similar safety profile.

Keywords: Hepatocellular carcinoma; Advanced; Hepatic arterial infusion chemotherapy; Transarterial chemoembolization; Prognosis; Efficacy

Core tip: This randomized controlled trial showed that the addition of oral S-1 (a composite preparation of a 5-fluorouracil prodrug) to transarterial chemoembolization followed by hepatic arterial infusion chemotherapy with oxaliplatin did not lengthen the survival time of patients with advanced hepatocellular carcinoma complicating portal vein invasion or extrahepatic metastasis, although it did appear to have moderately better anti-tumor activity. Overall, transarterial chemoembolization combined with hepatic arterial infusion chemotherapy was an effective and safe treatment for patients with advanced hepatocellular carcinoma with portal vein invasion or extrahepatic metastasis.