Observational Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jun 15, 2020; 12(6): 663-676
Published online Jun 15, 2020. doi: 10.4251/wjgo.v12.i6.663
Sorafenib combined with embolization plus hepatic arterial infusion chemotherapy for inoperable hepatocellular carcinoma
Bao-Jiang Liu, Song Gao, Xu Zhu, Jian-Hai Guo, Xin Zhang, Hui Chen, Xiao-Dong Wang, Ren-Jie Yang
Bao-Jiang Liu, Song Gao, Xu Zhu, Jian-Hai Guo, Xin Zhang, Hui Chen, Xiao-Dong Wang, Ren-Jie Yang, Department of Interventional Therapy, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing 100142, China
Author contributions: Liu BJ, Gao S, and Zhu X are the guarantors of integrity of the entire study, and they contributed to the statistical analysis and manuscript editing; all authors contributed to the study concept/design, data acquisition or analysis/interpretation, manuscript drafting or revision for important intellectual content, and approval of the final version of submitted manuscript; and agreed to ensure that any questions related to the work were appropriately resolved; Liu BJ, Gao S, Zhu X, and Zhang X contributed to the literature research; Liu BJ, Gao S, Zhu X, Zhang X, Chen H, Wang XD, and Yang RJ contributed to the clinical studies; Zhu X contributed to the experimental study. Liu BJ and Gao S contributed equally to this work.
Supported by Beijing Municipal Science and Technology Commission (Z181100010118001), Foundation of Chinese Geriatric Oncology Society (CGOS-01-2012-1-00800), National Key R and D Program of China (2017YFC0114004) and National Natural Science Foundation of China (81971717).
Institutional review board statement: This was a single-arm, single-institution, open-label phase II trial that was approved by the Research Ethics Committee of Peking University Cancer Hospital (2011110803).
Informed consent statement: All participants provided written informed consent for treatment according to the standard practices at our institution.
Conflict-of-interest statement: The authors have no conflicts of interest to disclose.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
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, PhD, Chief Doctor, Full Professor, Department of Interventional Therapy, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), No. 52, Fucheng Road, Haidian District, Beijing 100142, China. drzhuxu@163.com
Received: February 20, 2020
Peer-review started: February 20, 2020
First decision: April 18, 2020
Revised: May 8, 2020
Accepted: May 27, 2020
Article in press: May 27, 2020
Published online: June 15, 2020
Processing time: 115 Days and 23.3 Hours
Abstract
BACKGROUND

There is little evidence of combining sorafenib with hepatic arterial infusion chemotherapy (HAIC) after transarterial chemoembolization (TACE) for intermediate and advanced hepatocellular carcinoma (HCC). It is important to identify that patients with intermediate and advanced HCC are most likely to benefit from this combination therapy.

AIM

To investigate the safety and clinical outcomes of sorafenib combined with HAIC with folinic acid, 5-fluorouracil (5-FU), and oxaliplatin (FOLFOX) after TACE for intermediate and advanced HCC.

METHODS

This prospective phase II study enrolled patients with intermediate and advanced HCC who underwent treatment with sorafenib combined with TACE-HAIC. All patients initially received the standard 400 mg dose of sorafenib twice daily before TACE-HAIC. Participants at our institute with intermediate and advanced HCC underwent routine TACE. Then, the catheter used for embolization was kept in place in the hepatic artery, and oxaliplatin was intra-arterially administered for 6 h, followed by 5-FU for 18 h, and folinic acid was intravenously administered for 2 h. The primary endpoints were safety, as evaluated by the Common Terminology and Criteria for Adverse Events version 4.0, and 12-mo progression-free survival (PFS), as analyzed by the Kaplan-Meier method. As secondary endpoints, the objective response rate (ORR) was evaluated by the modified Response Evaluation Criteria for Solid Tumors, and survival time [overall survival (OS)] was analyzed by the Kaplan-Meier method.

RESULTS

Sixty-six participants at our institute with intermediate and advanced HCC were enrolled in this prospective study (mean age, 53.3 ± 11.7 years). Approximately 56.1% of participants had Barcelona Clinic Liver Cancer (BCLC) stage C disease, and 43.9% had BCLC stage B disease. The ORR was 42.4%. The disease control rate was 87.9%. The grade 3-4 toxicities consisted of thrombocytopenia (4.5%), neutropenia (3.0%), and elevated aspartate aminotransferase (12.2%). Hand-foot skin reaction was also observed (40.9%). The median PFS was 13.1 mo (13.5 mo in the BCLC stage B participants and 9.4 mo in the BCLC stage C participants). The 6-mo, 12-mo, and 24-mo PFS rates were 75.0%, 54.7%, and 30.0%, respectively. The median OS was 21.8 mo.

CONCLUSION

Sorafenib combined with HAIC (FOLFOX) after TACE may be a feasible treatment choice for intermediate and advanced HCC because this treatment met the prespecified endpoint of a 6-mo PFS rate exceeding 50% and had good patient tolerance. Prospective randomized controlled trials are needed to confirm the effect of this combination therapy.

Keywords: Hepatocellular carcinoma; Transcatheter arterial chemoembolization; Hepatic arterial infusion chemotherapy; Oxaliplatin; Fluorouracil; Sorafenib

Core tip: Both hepatic arterial infusion chemotherapy (HAIC) and sorafenib plus transcatheter arterial chemoembolization (TACE) combination therapy are widely used as a treatment of choice in patients with hepatocellular carcinoma (HCC) in Asia. However, the safety and efficacy of sorafenib combined with HAIC (folinic acid, 5-fluorouracil, and oxaliplatin) after TACE for intermediate and advanced HCC have not been firmly established. In the present study, we confirmed the efficacy and safety of this combination therapy. We believe that this study can help doctors and patients to select appropriate therapy.