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··1210002220033112【】-2VEGFＲ-2VEGF。20141017CFDA1.1。、CSCO、。【】Ｒ735.2A1009－0460201509－0841－0711.1。2015ACSCACancerJClin1201295、、73。WHO《2014》2201240%。《2015》34222.7/1017.9/103。10%65%～70%527.4%3-5。6。1.2Apatinib-2VEGFＲ-2“·”“·”ATPVEGFＲ-2VEGF。VEGFＲ-2FDA2015NCCN6VEGFＲ-2。。Ⅱ7141、850mgqd425mgbid3。FASOＲＲ。·148·20159209ChineseClinicalOncologySep．2015Vol．20No．9850mgqdOＲＲ6.38%425mgbid13%850mgqdmPFS3.7425mgbid3.21.4。Ⅲ850mgqd。Ⅲ8273850mgqd。FAS850mgqdmOS6.51.8P=0.014930%850mgqdmPFS2.61.8P＜0.0001OＲＲ2.84%0P=0.1695DCＲ42.05%8.79%P＜0.0001QoLP＞0.05。ⅡⅢAE9。AE、、、、、、、AE。、。CFDA201410171.1。CSCO、。22.1。2.2850mgqd。2.3。ECOG≥2、、、、500mgqd1～2。33.1≥5%、、、、。、。1250mg。、、。1NCI1～23～4≤1a1～23～4≤1aa1750mgqd2500mgqd3.23.2.1。Ⅱ/Ⅲ17.94%3～42.69%。。1～23～4。、。、、。3.2.2Ⅱ/Ⅲ10.31%3～41.35%。。·248·20159209ChineseClinicalOncologySep．2015Vol．20No．9。1～2、、、2、、。3～4。3.33.3.13.3.1.1VEGF/VEGFＲ10-12。Ⅱ/Ⅲ36.32%35.38%4。＞150/100mmHg。2。。/NO/PGI2、、、13-15。、、。3.3.1.2NCI16VEGF/VEGFＲ＜140/90mmHg。217。＜140/90mmHg。＞140/90mmHg、、18-19。《2010》20。ACEIAＲB20-21。CYP3A4CYP3A410。3～4/。922。2。2NCI－CTCAE4.01120～139mmHg80～89mmHg2140～159mmHg90～99mmHg3≥160mmHg≥100mmHg45－·348·20159209ChineseClinicalOncologySep．2015Vol．20No．93.3.23.3.2.1Ⅱ/Ⅲ44.36%31.79%。3。23-25。、。VEGF/VEGFＲ26。VEGF/VEGFＲ/。3.3.2.2。3327。、221/2441。3chronickidneydiseaseCKDGFＲml/min1.73m21GFＲGFＲ＞902GFＲGFＲ60～893GFＲGFＲ30～594GFＲGFＲ15～295GFＲ＜15＞2。＞211。28-29。ACEIAＲB。4。4NCI－CTCAE4.01+24＜1.0g2++241.0～3.4g2424324＞3.4g≤2233.3.33.3.3.1HFSＲ、、、、、。、30。Ⅱ/ⅢHFSＲ27.35%37.62%4HFSＲ31-32。HFSＲ2～3。HFSＲVEGF/VEGFＲ33HFSＲ·448·20159209ChineseClinicalOncologySep．2015Vol．20No．9。3.3.3.2、。、、34。HFSＲ、、5%35BB1、B6。。HFSＲ。3＞2HFSＲ1HFSＲ。＞2HFSＲ113HFSＲ。HFSＲ5。5NCI－CTCAE4．01、、、2、、、、B3、、、、、3.3.43.3.4.1Ⅱ/Ⅲ2.24%3.60%3、41.35%2.88%8.97%7.91%1。36-40。。VEGFVEGF/VEGFＲ10。3.3.4.21++2+33/4。PTINＲ3～4。。、、、。·548·20159209ChineseClinicalOncologySep．2015Vol．20No．94CFDA、。Ⅱ/Ⅲ、、、。Ⅳ、、、。1TorreLABrayFSiegelＲLetal．Globalcancerstatistics2012J．CACancerJClin201565287－108．2WorldHealthOrganization．Healthstatisticsandinformationsys-temsWHOmortalitydatabaseEB/OL．20142015-08-10．http//who．int/healthinfo/mortality_data/en/．3．2015EB/OL．20152015-08-10．http//．huaxia．com/sp/xwss/dlxw/2015/04/4355225．html．4．J．2014197408－427．5．2011EB/OL．2011-02-162015-08-10．http//．nhfpc．gov．cn/yzygj/s3585u/201103/96ce9016858d416f83da688df45e3f2e．shtml．6NationalComprehensiveCancerNetworkInc．NCCNclinicalpracticeguidelinesinoncologyGastriccancerVersion2.2015EB/OL．20152015-08-10．http//．nccn．org/professionals/physician_gls/pdf/gastric．pdf．7LiJQinSXuJetal．Apatinibforchemotherapy-refractoryadvancedmetastaticgastriccancerresultsfromarandomizedplacebo-controlledparallel-armphaseⅡtrialJ．JClinOn-col201331263219－3225．8QinSK．PhaseⅢstudyofApatinibinadvancedgastriccancerArandomizeddouble-blindplacebo-controlledtrialC．JClinOncol20143215Suppla4003．9．M．2015368－398．10MarietteHJoepHStefanSetal．CardiovascularandrenaltoxicityduringangiogenesisinhibitionclinicalandmechanisticaspectsJ．JHypertens200927122297－2309．11ＲiniBI．BiomarkersHypertensionfollowinganti-angiogenesistherapyJ．ClinAdvHematolOncol201086415－416．12KostasNEleniKParaskeviBetal．Bevacizumab-inducedhypertensionpathogenesisandmanagementJ．BioDrugs2011253159－169．13ＲoodhartJMLangenbergMHWitteveenEetal．Themolecu-larbasisofclasssideeffectsduetotreatmentwithinhibitorsoftheVEGF/VEGFＲpathwayJ．CurrClinPharmacol200832132－143．14EreminaVJeffersonJAKowalewskaJetal．VEGFinhibitionandrenalthromboticmicroangiopathyJ．NEnglJMed2008358111129－1136．15LankhorstSKappersMHvanEschJHetal．Hypertensionduringvascularendothelialgrowthfactorinhibitionfocusonni-tricoxideendothelin-1andoxidativestressJ．AntioxidＲed-oxSignal2014201135－145．16MaitlandMLBakrisGLBlackHＲetal．Initialassessmentsurveillanceandmanagementofbloodpressureinpatientsre-ceivingvascularendothelialgrowthfactorsignalingpathwayinhib-itorsJ．JNatlCancerInst20101029596－604．17IvanyiPWinklerTGanserAetal．Noveltherapiesinad-vancedrenalcellcarcinomaManagementofadverseeventsfromsorafenibandsunitinibJ．DtschArzteblInt200810513232－237．18LarochellePKollmannsbergerCFeldmanＲetal．Hyperten-sionmanagementinpatientswithrenalcellcancertreatedwithanti-angiogenicagentsJ．CurrOncol2012194202－208．19CohenＲBOudardS．Antiangiogenictherapyforadvancedrenalcellcarcinomamanagementoftreatment-relatedtoxicitiesJ．InvestNewDrugs20123052066－2079．·648·20159209ChineseClinicalOncologySep．2015Vol．20No．920．2010J．2011198701－741．21．2011J．20124231－39．22．J．20143412－9．23．J/OL．20152015-08-10．http//cancer．cmt．com．cn/detail/746299．html．24ZhuXWuSDahutWLetal．Ｒisksofproteinuriaandhyper-tensionwithbevacizumabanantibodyagainstvascularendotheli-algrowthfactorsystematicreviewandmetaanalysisJ．AmJKidneyDis200792186－193．25．J．201132219－24．26EreminaVBaeldeHJQuagginSE．ＲoleoftheVEGF--asigna-lingpathwayintheglomerulusevidenceforcrosstalkbetweencomponentsofthelomerularfiltrationbarrierJ．NephronPhysi-ol2007106232－37．27NationalKidneyFoundation．K/DOQIclinicalpracticeguidelinesforchronickidneydiseaseevaluationclassificationandstrati-ficationJ．AmJKidneyDis2002392Suppl11－266．28AminCWallenEPruthiＲSetal．Preoperativetyrosineki-naseinhibitionasanadjuncttodeb