抑那通治疗前列腺癌的新进展

抑那通治疗前列腺癌的新进展第1页/共51页AUA(2010)内分泌治疗新进展Radiotherapycombinedwithandrogendeprivationvs.androgendeprivationaloneinclinicallylocallyadvancedprostatecanerinamulticenterrandomisedphaseIIIstudyNicolasMottet,France.第2页/共51页AUA(2010)内分泌治疗新进展INTRODUCTIONANDOBJECTIVESInlocallyadvanceddisease,thecombinationofradiotherapy(RT)andandrogendeprivation(ADT)issuperiortoRTalone.ButADTwithananaloguehasneverbeencomparedtocombinedmodality.WereportaphaseIIIrandomisedtrialinlocallyadvancedPCa,comparingacombinedmodalityandADTonly.第3页/共51页AUA(2010)内分泌治疗新进展METHODSInthisFrenchmulticenter,open,randomisedtrial,patientslessthan80years,withhistologicallyconfirmedPCa,T3-4,orpT3(biopsy)N0M0wereincluded.Theywerecentrallyrandomisedin2parallelgroupstoeitherADTalone(leuprorelin11.25mgSR,1scinjectionevery3monthsfor3yearsorthesameADTcombinedwithRTstartingwithin3monthsover7weeks.第4页/共51页AUA(2010)内分泌治疗新进展RESULTSHTHT+RTPN131133MeanAge70.570.70.63MeanPSAbaseline51.7741.500.79MedianPFS(days)126425440.0005PFS(5year)(%)15.464.70.0005Biologicalprogression(%)71.519.5<0.0001Clinicalprogression(%)37.711.3<0.0001第5页/共51页AUA(2010)内分泌治疗新进展Prevalenceofmetabolicsyndromeinprostatecancerpatientsunderandrogendeprivationtherapy:interimresultsofacase-controlstudy.JorgeRopero,Barcelone,Spain.第6页/共51页AUA(2010)内分泌治疗新进展INTRODUCTIONANDOBJECTIVESCardiovascularmortalityisthemostimportantcauseofdeathinpatientswithprostatecancer(PC).Thedevelopmentofmetabolicsyndrome(MS)inpatientsundergoingandrogendeprivationtherapy(ADT)hasbeenrelatedwiththisincreaseinmortalityrate.TheaimofthisstudyhasbeentoconfirmthehypothesisthatADTincreasestheprevalenceofMS.第7页/共51页AUA(2010)内分泌治疗新进展METHODSAgroupof157patientswereenrolledinthisinterimanalysisofaprospectivecasecontrolstudy.53PCpatientsunderADTduringameantimeof52months(6to252)and104agematchedcontrolsevaluatedatthetimeofprostatebiopsy(52withcancerand52without)wereincluded.第8页/共51页AUA(2010)内分泌治疗新进展METHODSMSwasanalyzedaccordingtheATPIIIpanelcriteria:Fastingplasmaglucoselevel>110mg/dLserumtriglyceridelevel>150mg/dLserumhigh-densitylipoproteinlevel<40mg/dLwaistcircumference>102cmBloodpressureof>130/85mmHg.第9页/共51页AUA(2010)内分泌治疗新进展RESULTSMSwasdiagnosedin27ofthe53patientssubjectedtoADT(51.9%)whileitwasdetectedin35ofthe105age-matchedcontrols(33.3%),p=0.020.HowevertheprevalenceofMSwas35.8%(19/53)inmenwithoutPCand30.8%(16/52)inmenwithPC,p=0.365.第10页/共51页AUA(2010)内分泌治疗新进展CONCLUSIONAlthoughthelimitednumbercasesandcontrolsincludedinthisinterimanalysis,asignificantincreaseintheprevalenceofMSwasobservedinPCpatientssubjectedtoADT.第11页/共51页AUA(2010)内分泌治疗新进展MetabolicchangeafterandrogendeprivationtherapyinKoreanmenwithprostatecancerChangHooPark,Korea第12页/共51页AUA(2010)内分泌治疗新进展INTRODUCTIONANDOBJECTIVESInmenwithprostatecancer,Androgendeprivationtherapyshowsavarietywellrecognizedmetabolicalteration.TobettercharacterizethemetaboliceffectsofandrogendeprivationtherapyinKoreanmen,weevaluatedthechangesinfatthickness,bonemineraldensity(BMD),bodymassindex(BMI),andlevelsofhemoglobin(Hb)andcholesterol.Wealsocomparedthemwithdatafromhealthysubjects.第13页/共51页AUA(2010)内分泌治疗新进展METHODSFromDecember2002toDecember2008,148Koreanmentreatedwithleuprolidedepotandbicalutamideforprostatecancerand100healthysubjectswereinvestigatedincludedchangefrombaselinetomonth12infatthickness,bonemineraldensity(BMD),bodymassindex(BMI),andlevelsofhemoglobin(Hb)andcholesterol.第14页/共51页AUA(2010)内分泌治疗新进展RESULTSADTControlPN148100Fatthickness(mm)20.416.9<0.05BMD=bonemineraldensity0.910.94<0.05BMI(kg/m2)23.922.9<0.05Therearenosignificantchangesinhemoglobinandcholesterollevels.第15页/共51页AUA(2010)内分泌治疗新进展CONCLUSIONOurresultsshowthatKoreanmenwithprostatecancerhaveincreasedabdominalsubcutaneousfatandBMIandhavedecreasedBMDduringandrogendeprivationtherapy.Theseincreasestheriskofbonefractureandcomplicationrelatedobesity.Therefore,BMDwillbecheckedperiodicallyandcarryoutexerciseprogramtopreventionobesityduringandrogendeprivationtherapy.第16页/共51页AUA(2010)内分泌治疗新进展Sarcopeniainmenreceivingandrogendeprivationtherapyforprostatecancer:aprospective3-yearstudy.MatthewR.Smith,CA.第17页/共51页AUA(2010)内分泌治疗新进展INTRODUCTIONANDOBJECTIVESAndrogendeprivationtherapy(ADT)forprostatecancerdecreasesbonemineraldensityandincreasesfracturerisk.StudieswithlimitedsamplesizeandobservationalperiodshavereportedthatADTisalsoassociatedwithsarcopeniaorlossofmuscle(leanbodymass,LBM).WenowreporttheprospectivechangesinLBMinasubsetofmenfromthatstudy.第18页/共51页AUA(2010)内分泌治疗新进展METHODSMenundergoingADTfornonmetastaticprostatecancerat38centersinNorthAmericawererandomizedtodenosumaborplacebo.Atotalof248subjects(130denosumab,118placebo)withabaselineandwithatleast1on-studyLBMresultwereconsideredevaluableandincludedinthisanalysis.第19页/共51页AUA(2010)内分泌治疗新进展METHODSSubjectswerestratifiedatbaselinebyage(<70yearsvs≥70years)andbydurationofADTtreatment(≤6monthsvs>6months).LBMwasmeasuredbytotalbodydual-energyx-rayabsorptiometryatbaselineandat12,24,and36months.第20页/共51页AUA(2010)内分泌治疗新进展RESULTSFrombaselinetomonth12,meanLBMdecreasedsignificantlyby1.0%(p=.0004).SignificantdecreasesinLBMwerealsoobservedatmonth24(2.1%,p<.0001)andmonth36(2.4%,p<.0001).第21页/共51页AUA(2010)内分泌治疗新进展RESULTSMenaged≥70years(n=127)hadsignificantlygreaterchangesinLBMatallmeasuredtimepoints.At36months,LBMdecreasedby2.8%inmenaged≥70yearscomparedwithadecreaseof0.9%inyoungermen(p=0.035).第22页/共51页AUA(2010)内分泌治疗新进展CONCLUSIONThisisthelargestandlongestprospectivestudyundertakentodescribethenaturalhistoryofmusclelossinmenundergoingADTtherapyforprostatecancer.LBMsignificantlydecreasedat12,24,and36months.DecreasesinLBMweregreatestinoldermenandinthosewhohadshortdurationofADTatstudyentry.第23页/共51页AUA(2010)内分泌治疗新进展RecoveryoftestosteroneandPSAaftercessationoflongtermluteinizinghormonereleasinghormoneagonist(LHRH)therapyforprostatecancer:aprospectivetrial.MatthewMcIntyre,Charleston,SC第24页/共51页AUA(2010)内分泌治疗新进展INTRODUCTIONANDOBJECTIVESTheuseofhormonalmanipulationinthetreatmentofprostatecancerhasbeenanoptionsincethetimeofHugginsinitialdescription.However,manyquestionsremainregardingtimingofinitiation,andlengthoftreatmentintervalformedicallyinducedcastration.第25页/共51页AUA(2010)内分泌治疗新进展INTRODUCTIONANDOBJECTIVESTheeffectsoflongtermLHRHagonistonthehypothymalicpituitarygonadalaxisarealsonotcompletelyunderstood.WesoughttoexaminetheeffectsoflongtermLHRHagonistonrecoveryoftestosteroneandPSA.第26页/共51页AUA(2010)内分泌治疗新进展METHODSHormonalablationwasdiscontinuedandserialtestosteroneandPSAmeasurementswereobtainedonathreemonthlybasis.Patientswerecounseledregardingrestartinghormonaltherapyif2consecutiverisesinPSAwereobserved.Patientswereallowedtostayoffhormonesandonstudyiftheydesired.第27页/共51页AUA(2010)内分泌治疗新进展METHODSWeorganizedaprospectivetrialexaminingmenattheVeteransAdministrationHospitalwhohadbeenonatleast48monthsofanLHRHagonist.OtherinclusioncriteriawerethatPSAbelessthan3ng/ml,andnotrisingforthe2consecutivevaluespriortodiscontinuinghormones.第28页/共51页AUA(2010)内分泌治疗新进展RESULTSNineteenpatientswereenrolledinthestudybetween2007and2008.Themeanagewas75years.

Themeandurationofhormonaltherapywas88months.第29页/共51页AUA(2010)内分泌治疗新进展RESULTSTen(53%)patientswereonhormonesforbiochemicalrecurrence；Two(10%)formetastaticdisease；Seven(36%)asprimarytherapy.第30页/共51页AUA(2010)内分泌治疗新进展RESULTSEleven(58%)patientshad2consecutiverisesinPSA;Themeantimetoseetwoconsecutiveriseswas11months.第31页/共51页AUA(2010)内分泌治疗新进展RESULTSThemeantimeofftherapypriortoariseinPSA0.1ng/mlabovebaselineforallpatientsandthosewith2consecutiveriseswas15.4and9.5monthsrespectively.ThemeanbaselinePSA,meanPSAatone,andattwoyearsofftherapywas0.3ng/ml,1.1ng/ml,and5ng/mlrespectively.Meantestosteroneatbaseline,one,andtwoyearsofftherapywas13.9ng/ml,76ng/ml,and150.6ng/mlrespectively.第32页/共51页AUA(2010)内分泌治疗新进展RESULTSTwelve(63%)patientshadrecoveryoftestosteroneabove50ng/dl.Four(21%)patientsremainedcastrateofftherapyameanof20months.Themeantimetotestosteronerecoverywas12.8months.Two(10.5%)patientsinthestudyhavedied.Onedeathwasattributedtoprostatecancer.第33页/共51页AUA(2010)内分泌治疗新进展CONCLUSIONTherecoveryoftestosteroneandsignificantelevationsofPSAafterlongtermLHRHagonisttherapyissignificantlydelayedinmostpatients.Thishelpstosupporttheconceptofintermittentandrogenablationwhichhasbenefitsinqualityoflifeandreducedcostoftherapy.第34页/共51页Dataonfile手术去势的副作用增加心血管疾病和糖尿病发病率第35页/共51页Dataonfile手术去势的副作用增加骨折发病率第36页/共51页抑那通通过抑制雄性激素的作用而抑制大白鼠前列腺肿瘤的增殖