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

Ma X, Li RS, Wang J, Huang YQ, Li PY, Wang J, Su HB, Wang RL, Zhang YM, Liu HH, Zhang CE, Ma ZJ, Wang JB, Zhao YL, Xiao XH - Front Pharmacol (2016)

Bottom Line: 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.The 3-year SR was not improved.The combination therapy resulted in a reduction in AEs.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, 302 Military Hospital of People's Liberation ArmyBeijing, China; Pharmacy College, Chengdu University of Traditional Chinese MedicineChengdu, China.

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.

No MeSH data available.


Related in: MedlinePlus

Risk of bias assessment in the included trials. The quality assessment was performed by Review Manager 5.3 according to the Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0. The red square indicates a high risk of bias. The green square indicates a low risk of bias, and the blank square indicates an unclear risk of bias.
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Figure 3: Risk of bias assessment in the included trials. The quality assessment was performed by Review Manager 5.3 according to the Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0. The red square indicates a high risk of bias. The green square indicates a low risk of bias, and the blank square indicates an unclear risk of bias.

Mentions: The baseline characteristics of the included studies are presented in Supplementary Table S2. Among the 18 studies (Huang et al., 2006; Yang, 2006; Chen et al., 2007; Cao et al., 2009; Deng et al., 2009; Wang and Chen, 2009; Yu et al., 2009; Tong, 2010; Xu et al., 2010; Yu and Kang, 2010; Qu et al., 2011; Wang et al., 2011; Zhang and Tian, 2011; Zuo et al., 2011; Han et al., 2012; Li et al., 2013; Sun, 2014; Tian, 2014) conducted between 2006 and 2014, all were RCTs with a comparison between a combination of CKI and TACE and TACE treatment alone. The age of the patients ranged from 25 to 79 years. Seventeen studies reported the stages of HCC and 13 mentioned KPS. The TACE treatment regimen varied greatly. However, the combination of 5-FU, DDP, MMC, EPI or DDP in the TACE treatment was the most common regimen. One study did NR the embolizing agents of TACE. Lipiodol was the embolizing agent in the remaining studies. The dose of administered CKI ranged from 15 to 30 mL/day. In the majority of studies, CKI was administered for 15 days via intravenous drip (Table 1). All trials mentioned “randomization,” but only four trials stated the appropriate generation of the random allocation sequence (Yang, 2006; Wang and Chen, 2009; Yu and Kang, 2010; Zuo et al., 2011). No trials described information on allocation concealment and blinding. Seven trials (Yang, 2006; Chen et al., 2007; Wang and Chen, 2009; Xu et al., 2010; Qu et al., 2011; Zuo et al., 2011; Li et al., 2013) mentioned over exclusion of participants or drop-outs. Selective reporting was low for the 14 trials (Yang, 2006; Chen et al., 2007; Cao et al., 2009; Wang and Chen, 2009; Yu et al., 2009; Tong, 2010; Xu et al., 2010; Yu and Kang, 2010; Qu et al., 2011; Zuo et al., 2011; Han et al., 2012; Li et al., 2013; Sun, 2014; Tian, 2014) (Figure 3, Supplementary Figure S1).


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

Ma X, Li RS, Wang J, Huang YQ, Li PY, Wang J, Su HB, Wang RL, Zhang YM, Liu HH, Zhang CE, Ma ZJ, Wang JB, Zhao YL, Xiao XH - Front Pharmacol (2016)

Risk of bias assessment in the included trials. The quality assessment was performed by Review Manager 5.3 according to the Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0. The red square indicates a high risk of bias. The green square indicates a low risk of bias, and the blank square indicates an unclear risk of bias.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4814457&req=5

Figure 3: Risk of bias assessment in the included trials. The quality assessment was performed by Review Manager 5.3 according to the Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0. The red square indicates a high risk of bias. The green square indicates a low risk of bias, and the blank square indicates an unclear risk of bias.
Mentions: The baseline characteristics of the included studies are presented in Supplementary Table S2. Among the 18 studies (Huang et al., 2006; Yang, 2006; Chen et al., 2007; Cao et al., 2009; Deng et al., 2009; Wang and Chen, 2009; Yu et al., 2009; Tong, 2010; Xu et al., 2010; Yu and Kang, 2010; Qu et al., 2011; Wang et al., 2011; Zhang and Tian, 2011; Zuo et al., 2011; Han et al., 2012; Li et al., 2013; Sun, 2014; Tian, 2014) conducted between 2006 and 2014, all were RCTs with a comparison between a combination of CKI and TACE and TACE treatment alone. The age of the patients ranged from 25 to 79 years. Seventeen studies reported the stages of HCC and 13 mentioned KPS. The TACE treatment regimen varied greatly. However, the combination of 5-FU, DDP, MMC, EPI or DDP in the TACE treatment was the most common regimen. One study did NR the embolizing agents of TACE. Lipiodol was the embolizing agent in the remaining studies. The dose of administered CKI ranged from 15 to 30 mL/day. In the majority of studies, CKI was administered for 15 days via intravenous drip (Table 1). All trials mentioned “randomization,” but only four trials stated the appropriate generation of the random allocation sequence (Yang, 2006; Wang and Chen, 2009; Yu and Kang, 2010; Zuo et al., 2011). No trials described information on allocation concealment and blinding. Seven trials (Yang, 2006; Chen et al., 2007; Wang and Chen, 2009; Xu et al., 2010; Qu et al., 2011; Zuo et al., 2011; Li et al., 2013) mentioned over exclusion of participants or drop-outs. Selective reporting was low for the 14 trials (Yang, 2006; Chen et al., 2007; Cao et al., 2009; Wang and Chen, 2009; Yu et al., 2009; Tong, 2010; Xu et al., 2010; Yu and Kang, 2010; Qu et al., 2011; Zuo et al., 2011; Han et al., 2012; Li et al., 2013; Sun, 2014; Tian, 2014) (Figure 3, Supplementary Figure S1).

Bottom Line: 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.The 3-year SR was not improved.The combination therapy resulted in a reduction in AEs.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, 302 Military Hospital of People's Liberation ArmyBeijing, China; Pharmacy College, Chengdu University of Traditional Chinese MedicineChengdu, China.

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.

No MeSH data available.


Related in: MedlinePlus