Efficacy and safety of transcatheter arterial chemoembolization combined with ginsenosides in hepatocellular carcinoma treatment

Abstract

Background: Transcatheter arterial chemoembolization (TACE) is a standard therapy to treat hepatocellular carcinoma (HCC), but often limited for its complications. Ginsenosides, including total ginsenosides (GS), Rg3, Rh2 and CK, have been clinically used as adjuvants of TACE in HCC therapy. However, partial clinical observations concerning the efficacy and safety of the combinational treatment were contradictory.

Purpose: To investigate the efficacy and safety of TACE and ginsenosides combination for HCC therapy.

Methods: Randomized controlled trials (RCTs) regarding TACE and ginsenosides for HCC up to May 2021 were screened from six databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese VIP Information and Web of Science). The outcomes of tumor response, adverse reactions (ADRs), quality of life (QOL), survival rates (OS) and liver function were extracted and evaluated by meta-analysis, respectively.

Results: A total of 18 RCTs with 1308 HCC patients were enrolled, and most of the eligible studies had unclear bias risk. Compared with TACE, combining ginsenosides improved objective response rate [ORR, risk ratio (RR) 1.39, 95% confidence intervals (CI) 1.20∼1.61], disease control rate (DCR, RR 1.21, 95% CI 1.12∼1.30), QOL (RR 1.54, 95% CI 1.25∼1.90), one- (RR 1.37, 95% CI 1.16∼1.62) and two- (RR 1.43, 95% CI 1.06∼1.95) year OS, and A level of Child-pugh, as well as reduced the risks of nausea and vomiting, pyrexia, ache, hyperbilirubinemia, anorexia, fatigue, leukopenia, thrombocytopenia and myelosuppression. Subgroup analyses showed that both short- and long- treatment durations of ginsenosides enhanced the A level of Child-pugh, and reduced nausea and vomiting, ache and hyperbilirubinemia. Besides, combining Rg3 benefited DCR, ORR and QOL, and alleviated nausea and vomiting, hyperbilirubinemia, leukopenia, myelosuppression, thrombocytopenia and α-fetoprotein, while combining GS alleviated nausea and vomiting, ache and hyperbilirubinemia, combining Rh2 alleviated thrombocytopenia, and combining CK alleviated nausea and vomiting, pyrexia, ache and leukopenia, respectively.

Conclusion: The results suggested that combining ginsenosides could continuously benefit the efficacy and safety of TACE in HCC treatment, and Rg3 is the prior selection during the combination.

Keywords: Ginsenosides; Hepatocellular carcinoma; Meta-Analysis; Randomized controlled trial; Transcatheter arterial chemoembolization.