| BackgroundAs one of the most frequently diagnosed cancers,digestive system neoplasms are the first leading cause of cancer mortality and morbidity in China.Among them,the total morbidity of cases with gastric cancer,liver cancer and colorectal cancer accounts for 40.75%among the major malignancies.Recently,Chinese herbal injections(CHIs)widely used in clinics in China,and they have the advantages of rapid absorption and high-bioavailability.Especially,CHIs have anti-cancer benefits for treating tumors by reducing toxicity,enhancing efficacy when it combined with radiotherapy and chemotherapy.However,medical staff often need to choose better varieties from CHIs for treating digestive system neoplasms in clinical practice.With the increasing of different CHIs appliances in China,nevertheless,the limitation of traditional mata-analysis couldn't achieve the comparision for multiple treatments simultaneously.Given this,it's urgent for the researchers to carefully identify and select the optimal and specific CHIs;therefore,utilizing the new methods to compare the relative efficacy and safety of CHIs has important academic significance and clinical value.For this sake,we designed and implemented this network meta-analysis(NMA)which compared the efficacy and safety of CHIs for treating gastric cancer,esophageal cancer,liver cancer,colorectal cancer and pancreatic cancer as breakthrough points to come up with the optimal choice for future clinical practice,and facilitate the timely recommendations and the clinical rational drug use.Objective:The aim of our study is to investigate the comparative efficacy and safety of CHIs for treating gastric cancer,esophageal cancer,liver cancer,colorectal cancer and pancreatic cancer.Methods1.Network meta-analysisWe performed a broad literature search in in the domestic and foreign database to collect and identify the relative randomized controlled trials(RCTs).The quality assessment was conducted by the Cochrane risk of bias tool for the included RCTs.Furthermore,the Bayesian framework was adopted for the implementation of NMA through Stata and WinBUGS software.The results of different outcomes are calculated as odds ratio(OR)with 95%credible intervals(CIs),additionally,the ranking probability of each treatment was produced by the surface under the cumulative ranking curve(SUCRA).2.Literature reviewThe method of literature review and data mining was utilized to statistical analyze the retrieved literature,including the basic product information of different CHIs and the related published systematic reviews or meta-analyses focusing on CHIs against neoplasms.Results1.The network meta-analysis result of CHIs for treating gastric cancerIn the terms of the network meta-analysis of CHIs combined with FOLFOX regimen for treating gastric cancer,a total of 2316 records were searched,ultimately,and 81 eligible RCTs involving 15 types of CHIs and 5978 patients were included.The results demonstracted that patients who received Shengqifuzheng+ FOLFOX,Compound kushen+ FOLFOX,Huachansu+ FOLFOX,Astragalus+ FOLFOX,Kangai+ FOLFOX,and Lentinan injection +FOLFOX could significantly improve clinical efficacy than using FOLFOX single,and their ORs and 95%CIs were 1.57(1.19,2.09),2.12(1.62,2.78),1.72(1.08,2.80),3,06(1.01,8.99),2.01(1.52,2.70),and 1.99(1.20,3.38),respectively.Furthermore,the therapy of Aidi+FOLFOX,Shenqifuzheng+ FOLFOX,Compound Kushen+ FOLFOX,Huachansu+ FOLFOX,Astragalus polysaccharides+ FOLFOX,Kangai+ FOLFOX,Ginseng polysaccharide+FOLFOX,Lentinan+ FOLFOX,Xiaoaiping+ FOLFOX,and Shenmai injection + FOLFOX could also achieve a higher performance status compared with FOLFOX regimen alone.Similarly,patients who received CHIs combine with FOLFOX regimen were associated with a significantly decrease the incidence of leucopenia,gastrointestinal reaction and hepatic dysfunction.For the network-analysis of CHIs combined with XELOX regimen for patients with gastric cancer,26 eligible RCTs involving 13 types of CHIs and 2154 patients.The results suggested that Shenqifuzheng+ XELOX,Huachansu+XELOX,Kangai+ XELOX,Javanicaoil emulsion+ XELOX,Aidi injection+ XELOX might be the optimal treatment for liver cancer in improving the performance status than using XELOX regimen single,with OR and 95%CI of 2.74(1.24,6.17),8.27(1.74,42.43),4.28(1.80,10.48),5.14(1.87,16.28),0.20(0.090,0.44),respectively..At the aspects of ADRs,Compound kushen+ XELOX,Lentinan+ XELOX,Xiaoaiping injection + XELOX could obviously relieve leukopenia than only receiving XELOX regimen,and their ORs and 95%CIs were 5.62(1.41,36.24),8.16(2.25,29.43),5.69(1.85,15.77).Furthermore,Disodium cantharidinate and vitamin B6+XELOX,Shenqifuzheng+ XELOX,Kangai+ XELOX,Lentinan + XELOX could obviously relieve the nausea and vomiting than receiving the XELOX regimen alone,with ORs and 95%CIs of 5.29(1.30,23.96),2.50(1.16,5.26),2.42(1.06,5.63),9.04(3.24,26.73).Nevertheless,CHIs combined with XELOX regimen did not confer higher clinical effectiveness rate over receiving XELOX regimen alone,without statistically significant between-group differences.2.The network meta-analysis result of CHIs for treating esophageal cancerWith regard to the network meta-analysis of CHIs in combination with radiotherapy(RT)for treating esophageal cancer,a total of 697 articles were retrieved via a primary search of literature databases.Ultimately,55 RCTs involving 4114 patients and 12 types of CHIs were identified.The results demonstrated that Aidi+ RT,Disodium Cantharidinate and Vitamin B6+RT,Compound Kushen+ RT,Huachansu+ RT,Astragalus polysaccharides+ RT,Kangai+RT,Elemene+ RT experienced better clinical effectiveness rates than the control group that received the RT alone.And Aidi+ RT,Compound Kushen+ RT,Astragalus polysaccharides+RT,Kangai+ RT,Lentinan + RT,Javanica oil emulsion+ RT achieved superior improvement in performance status relative to patients only received RT;these between-group differences were statistically significant.Moreover,on the basis of RT also received Aidi,Shenqifuzheng,Compound Kushen,Kangai,Lentinan,Javanica oil emulsion clearly stood better with regard to relieve leukopenia than receiving RT alone;on the basis of RT also received Aidi,Compound kushen,Astragalus polysaccharides,Javanica oil emulsion injection were associated with a lower incidence of radioactive esophagitis than only receiving RT.As for the network meta-analysis of CHIs in combination with chemotherapy(CT)for treating esophageal cancer,a total of 697 articles were retrieved via a primary search of literature databases.Ultimately,29 RCTs involving 1967 patients and 8 types of CHIs were identified.The results indecated that Compound Kushen+ CT,Huachansu+ CT could achieve higher clinical effectiveness rates than receiving CT alone.And Aidi+ CT,Shenqifuzheng+CT,Compound Kushen+ CT,Shenfu+ CT could improve the performance status of patients with esophageal cancer;statistically significant differences were observed between groups.Furthermore,Aidi+ CT,Shenqifuzheng+ CT,Compound Kushen+ CT,Shenfu+ CT,Xiaoaiping+ CT were associated with a lower incidence of leukopenia than only receiving RT.3.The network meta-analysis result of CHIs for treating liver cancerIn light of the network meta-analysis of CHIs combined with transcatheter hepatic arterial chemoembolization(TACE)for liver cancer,a total of 105 suitable RCTs were identified,with data for 7683 patients and 13 types of CHIs.The results indecated that compared with the TACE alone,Javanica oil emulsion,Huachansu or Aidi injection combined with TACE could improve 1-year survival rate.Kanglaite,Shenmai,Huachansu or Aidi injection plus TACE could improve 2-year survival rate.Compound Kushen,Javanica oil emulsion,Aidi,Kanglaite,Kangai,Huachansu,Astragalus polysaccharide injection plus TACE yielded significantly higher probability of improving the clinical effective rate.Aidi,Compound Kushen,Javanica oil emulsion,Xiaoaiping,Kanglaite,Shenmai,Shenqifuzheng,Delisheng,Huachansu,Astragalus polysaccharide injection combined with TACE yielded significantly higher probability of improving the performance status.4.The network meta-analysis result of CHIs for treating colorectal cancerAs for the network meta-analysis of CHIs combined with the FOLFOX regimen for the treatment of colorectal cancer,a total of 820 records were searched among several electronic databases,finally,60 eligible articles involving 4849 participants and 12 CHIs were included.The results of the network meta-analysis demonstrated that compared with the FOLFOX regimen alone,the FOLFOX regimen combined with Delisheng,Kanglaite,Shenqifuzheng,or Aidi injections could produce improved clinical effects and the FOLFOX regimen combined with Delisheng,Xiaoaiping,Lentinan,Kangai,Shenqifuzheng,or Aidi injections could improved the performance status.5.The network meta-analysis result of CHIs for treating pancreatic cancerAs for the network meta-analysis of CHIs combined with the chemotherapy for the treatment of pancreatic cancer,a total of 278 records were identified through the initial searching,and 22 eligible RCTs involving 1329 patients and 9 CHIs were included.The results of the network meta-analysis suggested that compared with the chemotherapy alone,Compound Kushen,Kangai or Kanglaite injection combined with chemotherapy yielded significantly higher probability of improving performance status.Aidi injection combined with chemotherapy was more effective in relieving leucopenia than using chemotherapy single.And these between-group differences were considered as statistically significant.Whereas CHIs combined with chemotherapy could not achieve a higher clinical total clinical rate,and cond not remarkably relieve nausea and vomiting for patients with pancreatic cancer.ConclusionThe combination of CHIs and radiotherapy or chemotherapy was beneficial for patients with digestive system neoplasms,namely CHIs combined with radiotherapy or chemotherapy could achieve the significant improvement in clinical effective rate and performance status,and relieve ADRs.The network meta-analysis results suggested that ? For gastric cancer,Astragalus polysaccharides+ FOLFOX,and Kangai+ FOLFOX seemed the optimal therapies in improving clinical efficacy and performance status;Astragalus polysaccharides+ FOLFOX was superior in reducing leucopenia and gastrointestinal reaction;Disodium Cantharidinate and Vitamin B6+ FOLFOX was associated with favorable effects in reducing gastrointestinal reaction and hepatic dysfunction.By contrary,receiving FOLFOX regimen single was proved to rank the worst for these outcomes.Besides,CHIs combined with XELOX regimen could provide therapeutic benefits for patients with gastric cancer.Among 13 types of CHIs,Javanica oil emulsion and Compound Kushen injection is the optimal treatment in improving the clinical effectiveness rate and performance status,and Lentinan injection was superior in relieving ADRs.? At the aspects of esophageal cancer,Compound Kushen injection plus radiotherapy yielded significantly higher probability of improving the clinical effective rate and performance status.Moreover,Compound Kushen injection plus chemotherapy yielded significantly higher probability of improving the clinical effective rate and performance status,and Compound Kushen injection plus chemotherapy was associated with the optimal treatment for relieving leucopenia and gastrointestinal reaction.? With regards to liver cancer,receiving Javanica oil emulsion,Huachansu injection plus TACE could be effective for patients with liver cancer in improving survival rate.Kanglaite,Astragalus polysaccharide injection plus TACE seemed the optimal in improve the clinical effective rate and performance status.And Shenmai injection combined with TACE was superior to reducing ADRs.?As for colorectal cancer,Compound Kushen injection combined with the FOLFOX regimen against colorectal cancer might be associated with the higher clinical effectiveness rate,the substantially improvement of performance status and obvious relieving ADRs compared to other CHIs groups.? In terms of pancreatic cancer,the chemotherapy alone and Huachansu injection combined with the chemotherapy were inferior to relieve ADRs than the other CHIs plus chemotherapy for patients with pancreatic cancer.Aidi,Disodium cantharidinate and vitamin B6 were the most beneficial CHIs for alleviating leukopenia in combination with the chemotherapy.Shenqifuzheng was associated with having a good effect of relieving nausea and vomiting.Nevertheless,our findings were warrant to be supported by prospectively designed,large-sample and multi-center RCTs. |
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