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1、AbstractABSTRACTObjective:Althoughtheapplicationofbevacizumabtotraditionalchemotherapyschemeplaysasignificantroleinfirst-linetreatmentofadvancedstagemalignanttumor,randomizedcontrolledtrials(RCTs)ofapplyingbevacizumabinpatientswithmetastaticcolorectalcancerhaverep
2、ortedconflictingresults.Andtheefficacyandtoxicityofaddingdifferentdosagesbevacizumabtochemotherapyregimenformetastaticcolorectalcancerarestillunclear.Therefore,ourresearchgroupconductedthismeta-analysistoassesstheefficacyandtoxicityofbevacizumabatdifferentdosagesa
3、ddedtofirst-linechemotherapyschemeformetastaticcolorectaladenocarcinomapatients.Method:WesearchedPubMed/MEDLINE,ASCO,EMBASEandCochranedatabasesetctoselectthequalifiedstudies.Result:Finally,eighttrials,contained3265patients,weremeettherequirement.Thepooledoutcomeme
4、asurementsincludedprogression-freesurvival(PFS),overallsurvival(OS),overallresponserate(ORR),grade3-5toxicitiesandtreatment-relatedmortality.Hazardratios(HR)andriskratio(RR)withtheircorresponding95%confidenceintervals(95%CI)wereusedforthemeta-analysis.Asaresult,th
5、eapplicationofbevacizumabtofirst-linechemotherapytreatmentsignificantlyprolongedPFS(fixedeffect:HR=0.50;95%CI:0.42-0.60;P<0.001)andincreasedOS(fixedeffect:HR:0.67;95%CI:0.60-0.76;P<0.001)aswellasORR(fixedeffect:RR=1.41;95%CI=1.20–1.65;P<0.001)at5mg/kg,butthismeta-
6、analysisrevealednostatisticaladvantageatdoseof7.5mg/kg.Ontoxicity,theriskofhypertensionwassignificantlyincreasedinbevacizumabgroupat5mg/kg,aswellasproteinuriaanddiarrheaat7.5mg/kg.However,theproportionoftreatment-relatedmortalitywasnotincreasedatbothdosages.Conclu
7、sion:Thismeta-analysissuggestedthatlow-dosagebevacizumabnotonlyincreasedtheOS,PFSandORRformetastaticcolorectaladenocarcinomaIII万方数据Abstractpatients,butalsohadlowrisksofsomeadverseevents(AEs)comparedwithhigh-dosagebevacizumab.Therefore,bevacizumabtreatmentwith5mg/k
8、gshouldbetakenintoconsiderationwhenselectingtheapplicableup-to-datetargetedtherapy.Keywords:metastaticcolorectalcarcinoma,bevacizumab,meta-analysis,toxi