A Systematic Review And Meta-analysis Of Traditional Insect Chinese Medicines Combined Chemotherapy For Non-surgical Primary Liver Cancer Therapy

Background:As one of the most important diseases that endanger human life and health,primary liver cancer has increased its morbidity and mortality year by year,and has a poor clinical prognosis.Western medical treatment of non-surgical primary liver cancer has many side effects,high cost and limited clinical benefits,which has limited the clinical application.As a representative of the traditional Chinese medicine and the complementary and alternative medicine,traditional insect Chinese medicines and related preparations have been widely applied in the treatment of non-surgical primary liver cancer,and have been confirmed by clinical reports and experimental studies.However,there is lack of clinical data to comprehensively evaluate the efficacy and safety of traditional insect Chinese medicines,and there is no overall assessment of the evidence-based medical evidence for the treatment of non-surgical primary liver cancer by traditional insect Chinese medicines.Objectives:To further evaluate the clinical efficacy and safety of traditional insect Chinese medicines and related preparations,we conducted a systematic review and Meta-analysis of randomized clinical trials(RCTs)based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)statement.Method:RCTs that meet the requirements were searched based on standardized searching rules in mainstream medical databases from the inception up to July 2017.According to the inclusion and exclusion criteria,eligible studies were included for baseline data analysis and risk of bais assessment by Cochrane collaboration's tool assessment.Then we made Meta-analysis and network Meta-analysis to evaluate the efficacy and safety of traditional insect Chinese medicine.Meta-regression analysis was performed for studies with higher heterogeneity.Funnel plots and Egger and Begg's tests were used to evaluate publication bias and the sensitivity analysis were used to evaluate the stability.Results:Ultimately,a total of 64 articles were enrolled in this Meta-analysis based on the including and excluding rules.We found that traditional insect Chinese medicines and related preparations combined chemotherapy show significantly effectiveness and safety in objective response rate improvement(RR=1.31,95%CI=[1.23,1.40],P<0.01),survival time extension[12 months(RR=1.43,95%CI=[1.33,1.54],P<0.001);18 months(RR=2.62,95%CI=[1.70,4.05],P<0.001);24 months(RR=1.71,95%CI=[1.52,1.93],P<0.001);36 months(RR=1.93,95%CI=[1.55,2.39],P<0.001)],amelioration for life quality[QoL scores improvement(RR=1.76,95%CI=[1.56,1.99],P<0.001);KPS improvement(RR=1.84,95%CI=[1.42,2.39],P<0.001);AFP improvement(RR=1.61,95%CI=[1.36,1.90],P<0.001)],improvement of immune function[CD3+(Std.MD=1.52,95%CI=[1.05,1.98],P<0.001);CD4+(Std.MD=2.52,95%CI=[1.25,3.25],P<0.001);CD4+/CD8+(Std.MD=1.55,95%CI=[0.64,2.47],P=0.0008<0.01);NK(Std.MD=1.79,95%CI=[0.49,3.09],P=0.007<0.01)]and reduction of therapeutic toxicity[WBC decrease(RR=0.72,95%CI=[0.55,0.94],P=0.01<0.05);gastrointestinal adverse reactions(RR=0.65,95%CI=[0.55,0.76],P=0.001<0.05);liver damage(RR=0.54,95%CI=[0.31,0.94],P=0.03<0.05)].Meta regression-analysis was conducted for the studies with high statistical heterogeneity(I~2>50%).No studies were found the source of heterogeneity except for the results of gastrointestinal side effect suggesting that the source may be drug and place factors.Although the results of Egger and Begg's test and funnel plot reveal the study has certain degree of publication bias,the sensitivity analysis clearly illustrated the stability of study.Network Meta-analysis and radar chart both show the Cinobufotalin was the most frequently used traditional insect Chinese medicines in the experimental group,while TACE was the most frequently used western medical method in the control group.Conclusion:We consider that traditional insect Chinese medicines and related preparations should be recommended as auxiliary therapy combined chemotherapy for non-surgical primary liver cancer.However,due to the quality limitations of the included studies,more high-quality clinical research evidence is needed in the future to provide reliable evidence-based medical evidence.