The Therapeutic Efficacy and Safety of Compound Kushen Injection Combined with Transarterial Chemoembolization in Unresectable Hepatocellular Carcinoma: An Update Systematic Review and Meta-Analysis

Abstract

Background: Compound Kushen Injection (CKI) is a Chinese patent medicine approved by the China Food and Drug Administration for the treatment of various types of solid tumors. CKI, combined with transarterial chemoembolization (TACE), is believed to increase the therapeutic efficacy of unresectable hepatocellular carcinoma (HCC). We report an updated and extended meta-analysis with detailed outcomes of both the efficacy and adverse events (AEs) of CKI combined with TACE therapy.Materials and methods: Electronic databases, including PubMed, Embase, the Cochrane Library, the Chinese Biomedical Database (CBM), Wanfang, the VIP medicine information system (VMIS) and the China National Knowledge Infrastructure (CNKI), were examined for relevant articles before November 13, 2015. An odds ratio (OR) was used to estimate tumor response (TR), Karnofsky Performance Scale (KPS) improvement, Child-Pugh (CP) improvement, survival rate (SR) and AEs. A publication bias and a subgroup analysis were also assessed.Results: Eighteen studies, with a total of 1,338 HCC patients who met the criteria for the meta-analysis, were included. TR, KPS improvement and CP improvement were significantly enhanced for the combination therapy compared to TACE alone (OR = 1.84, 95% CI: [1.46, 2.33], P < 0.00001; OR = 2.37, 95% CI: [1.76, 3.18], P < 0.00001; OR = 1.81, 95% CI: [1.08, 3.03], P = 0.02, respectively). The combination therapy was associated with an improvement in 1-year and 2-year SRs but not an improved 3-year SR (OR = 2.40; 95% CI: [1.59, 3.62], P < 0.0001; OR = 2.49, 95% CI: [1.24, 5.00], P = 0.01; OR = 2.49, 95% CI: [0.94, 6.61], P = 0.07, respectively). A safety analysis indicated that AEs (including nausea/vomiting, fever, hepatalgia, increased transaminase, increased bilirubin and leukopenia) were reduced for the combination treatment compared to TACE alone.Conclusion: The combination treatment of TACE and CKI was associated with improved TR, KPS and CP improvement and improved 1- and 2-year SRs in patients with unresectable HCC. The 3-year SR was not improved. The combination therapy resulted in a reduction in AEs. The findings of this study should be interpreted with caution because of the small sample size and study limitations.

Compound kushen injection relieves tumor-associated macrophage-mediated immunosuppression through TNFR1 and sensitizes hepatocellular carcinoma to sorafenib

“…17 The application of CKI for the treatment of a variety of cancer types has also been studied in breast cancer, 19 colon cancer, 20 nonsmall cell lung cancer, 21 acute leukemia, 22 and HCC. [23][24][25] Sorafenib, the first frontline drug, has been widely used for advanced HCC therapy for a long time. However, only on July 17, 2020 by guest.…”

“…17 21 22 For HCC, CKI increases the therapeutic efficacy of TACE against unresectable liver cancer. [23][24][25] However, the effect of CKI on tumor immunity and its underlying mechanism remain poorly understood. Particularly, considering the different modes of action of immunotherapeutic (microenvironment-targeted) and chemotherapeutic drugs (tumor cell-targeted), it is necessary to illustrate the potential efficacy of combined treatment with CKI and chemotherapeutic drugs against HCC.…”

Prognostic significance of miR-1268a expression and its beneficial effects for post-operative adjuvant transarterial chemoembolization in hepatocellular carcinoma

“…Because of its very poor prognosis resulting from metastasis and recurrence, it has been regarded as the third most common cause of death from cancers worldwide1. In the past decades, several new treatment options have been developed and recommended for patients with HCC2345. Among these treatments, the transarterial chemoembolization (TACE) is reported to be an effective treatment for advanced-stage HCC patients, especially for those cases with 3- to 5-cm tumors56.…”

Understanding the Mechanistic Contribution of Herbal Extracts in Compound Kushen Injection with Transcriptome Analysis

“…It is widely used as an adjuvant medicine in the treatment of carcinomas for pain relief, activation of innate immune response and reduced side effects in cancer therapy 12,13 . Our previous results have shown that CKI suppresses the growth of cancer cells by inhibiting cell cycle, energy metabolism, and DNA repair pathways 11,14 .…”