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
ARTICLE HIGHLIGHTS
Research background

The prognosis for patients with advanced hepatocellular carcinoma (HCC) characterized by vascular tumor invasion and/or extrahepatic metastasis is almost always very poor. Systemic therapy with sorafenib was the only recommended first-line therapy for these patients at the beginning of this study. Transarterial chemoembolization (TACE) is recommended for the treatment of patients with intermediate stage HCC, although it has been investigated in patients with more advanced disease with equivocal results. Hepatic arterial infusion chemotherapy (HAIC) has shown promising local benefits for advanced HCC. S-1 has proven to be a convenient oral chemotherapeutic agent with definite efficacy against advanced HCC.

Research motivation

Sorafenib had shown limited benefit and was not easily accessible for many patients due to high cost. Other therapeutic approaches such as TACE and HAIC have been investigated in clinical practice, particularly in the Asia Pacific region. However, equivocal data mean that these approaches remain controversial in patients with advanced HCC. Novel treatment strategies are therefore being sought, and TACE followed by HAIC with oxaliplatin has shown promising preliminary results.

Research objectives

To evaluate the efficacy and safety of treatment with TACE followed by oxaliplatin-based HAIC, with or without oral S-1, in advanced-stage HCC with portal vein invasion and/or extrahepatic metastasis, we use progression-free survival (PFS) as the primary endpoint and overall survival (OS), objective response rate, disease control rate and safety as the secondary endpoints.

Research methods

In this single-center, open-label, randomized, controlled trial, patients with advanced HCC were randomized (1:1) to receive TACE (epirubicin 20-40 mg) followed by oxaliplatin-based HAIC (oxaliplatin 85 mg/m2) either with (TACE/HAIC + S-1) or without (TACE/HAIC) oral S-1 60 mg twice daily.

Research results

Our results showed that the addition of oral S-1 to TACE followed by HAIC with oxaliplatin did not lengthen PFS and OS, although numerically higher objective response rate and disease control rate were observed for TACE/HAIC with S-1 vs without S-1 (30.9% vs 18.4% and 72.7% vs 56.7%). Both treatment regimens were similarly well tolerated by patients.

Research conclusions

In conclusion, TACE combined with HAIC was an effective and safe treatment for patients with advanced HCC with portal vein invasion and/or extrahepatic metastasis, although the addition of S-1 to sequential TACE and oxaliplatin-based HAIC did not lead to improved PFS or OS.

Research perspectives

Given that systemic therapy has only limited benefit and is inaccessible for patients with advanced HCC in many countries, and based on the promising results achieved with TACE and HAIC, identifying a strategy to derive the optimal benefit from these approaches remains an unmet need.