Meta-analysis Of Recombinant Human Endostatin Combined With TACE Versus TACE Alone For Itermediate-advanced Hepatocellular Carcinoma

Background:Primarylivercancer(PLC)isoneofthemostcommonmalignanciesin China,and intermediate-advanced hepatocellular carcinoma is often diagnosedmostly.Transcatheterarterialchemoembolization(TACE)is the firsttreatmentforunresectable hepatocellularcarcinoma(u HCC).Recombinanthumanendostatin(rh ES)isanewtypeofvascularendothelial inhibitordevelopedby Chinesescholarsindependently.Inrecentyears,there isagradualincreaseinthetreatmentofu HCCwithrh EScombinedwith TACE,which produces the good efficacy and little toxicity.However,the combinationregimensremaincontroversialandevidencebasedmedicineis stillunclear.Objectives:This Meta-analysisevaluatestheefficacyandsafetyofrh EScombinedwith TACEversus TACEaloneforintermediate-advancedhepatocellularcarcinoma,andprovidesausefulreferenceforclinicalpractice.Methods:1.Therelevantcontrolledtrialsaboutrh EScombinedwith TACEversus TACEaloneinthetreatmentofu HCCwereretrievedfrom thedatabasesof Pub Med,Science Direct,Cochrane Library,China National Knowledge Infrastructure(CNKI),Chinese Bomedical Lterature Di i atabase(CBM),Wan Fangand VPDatabase.Theretrievaltimelimitedwasfrom I thedatabase constructionto Jnuary2018.a2.Theshort-termtherapeuticefficacy,thelong-termtherapeuticefficacy,alpha-fetoprotein(AFP)negativeconversionratio,thechangeof KPSscores,thechangeofserum vascularendothelialgrowthfactor(VEGF)levelandthe common adverse reactions(Myelosuppression,Gastrointestinalreaction,Liverfunctiondamage,cardiotoxicity)werecomparedbetweenthe2groups.3.Afterdataextraction,thequalityoftheincludedstudieswasevaluated byusingbiasriskassessmenttoolsprovidedbythe Cochranecollaboration,andthe Meta-analysiswasperformedbyusing Rv Me an5.3software.The enumerationdatawereexpressedasriskratio(RR)and95% confidence intervals(CI),andthemeasurementdatawereexpressedasstandardized meandifference(SMD)and95%CI.Results:1.26 controlledtrialswereincludedinthis Meta-analysis.Andtherewere1469 cases,ofwhich742casesinrh EScombinedwith TACEgroupand727 casesinTACEalonegroup.2.Abouttheshort-term therapeuticefficacy,rhEScombinedwithTACE hadanoveralladvantageover TACEaloneintermsofobjectiveresponserate(ORR)(64.11% vs40.24%,RR=1.59,95%CI:1.41~1.79,P<0.00001).The short-term therapeuticefficacyofeachsubgroupwasanalyzed:the ORRof rh ES combined with TACE in intrahepatic arterialembolization group,intrahepaticarterialpumpgroupandintravenousinfusiongroupwasbetter thanthe TACEalone(RRintrahepaticarterialembolizationgroup=1.68,95%CI:1.36~1.95,P<0.00001;RRintrahepaticarterialpumpgroup=1.49,95%CI:1.24~1.79,P<0.0001;RRintravenousinfusiongroup=1.69,95%CI:1.22~2.34,P=0.002),and RRintravenousinfusion group>RRintrahepatic arterial embolization group> RR all>RRintrahepatic arterial pump group(1.69>1.63>1.59>1.49).3.AFPnegativeconversionratioofHCCpatientstreatedwithcombined rh ESand TACEwerehigherthanthosetreatedwith TACEalone(53.8%vs25.74%,RR=2.06,95%CI:1.49~2.86,P<0.0001).Andthechangesof KPSscore aftertherapywerealsohigherthan TACEalone(SMD=1.15,95%CI:0.39~1.91,P=0.003).4.Therewasnosignificantdifferenceinthechangesofserum VEGF levelonthe3dayaftertherapy(SMD=0.01,95%CI:-0.19~0.22,P=0.91),butthe serum VEGFleveldecreasedsignificantlyonthe7,14,21and28daysafteroperation,and the difference was statisticallysignificant(SMD=-0.82,95%CI:-1.46~-0.17,P=0.01;SMD=-3.68,95%CI:-7.01~-0.35,P=0.03;SMD=-1.62,95%CI:-3.18~-0.06,P=0.04;SMD=-2.64,95%CI:-4.28~-1.01,P=0.001).5.Only2studieswerereportedforprogressionfreesurvival(PFS)and overallsurvival(OS).Respectively,median PFSwasincreasedby4months(9vs5months),4months(10vs7months),andthedifferencewasstatistically significant(P<0.05).Median OSwasincreasedby2.53months(10.64vs8.11months),1.5months(14.0vs12.5months),however,thedifferencewasno statisticallysignificant(P>0.05).Andthe Meta-analysisshowedthe1 year OS rateofrh EScombinedwith TACEwashigherthan TACEalone(73.26%vs68.18%),however,thedifferencewasnostatisticallysignificant(RR=1.07,95%CI:0.89~1.29,P=0.47).6.Aboutthecommonadversereactions,Myelosuppression(RR=1.05,95%CI:0.76~1.45,P=0.76),Gastrointestinal reaction(RR=1.30,95%CI:0.97~1.75,P=0.08),Liverfunctiondamage(RR=1.11,95%CI:0.87~1.40,P=0.41)werenostatisticallysignificantdifferences.Conclusion:1.Rh EScombinedwith TACEcanimprovetheshort-term therapeutic efficacyofu HCC more than TACE alone.In subgroup analysis ofthe short-term therapeuticefficacy:The use ofrh ES in intrahepaticarterial embolizationgroupandintravenousinfusiongrouphavebettertherapeutic efficacy.2.AFPnegativeconversionratioofthecombinationregimenisalso higheraftertherapy,andthecombinationregimencanimprovethe KPSscore.soastoimprovethepatient'slivingcondition.3.ThecombinationregimencaneffectivelyinhibitincreasedVEGFlevels after TACEtreatment,soastoinhibittumorangiogenesis.4.Theresultsofthelong-term therapeuticefficacy(PFS,OS)needmore clinicalstudiestoconfirmfurther.5.Theincidenceofthecommonadversereactions(Myelosuppression,Gastrointestinalreaction,Liverfunctiondamage)aresimilarbetweenrh ES combinedwith TACEand TACE alone.