抑那通治疗前列腺癌的最新进展-expert.ppt

抑那通治疗前列腺癌的新进展 北京大学第三医院黄毅 AUA 2010 内分泌治疗新进展 Radiotherapycombinedwithandrogendeprivationvs androgendeprivationaloneinclinicallylocallyadvancedprostatecanerinamulticenterrandomisedphaseIIIstudyNicolasMottet France AUA 2010 内分泌治疗新进展 INTRODUCTIONANDOBJECTIVESInlocallyadvanceddisease thecombinationofradiotherapy RT andandrogendeprivation ADT issuperiortoRTalone ButADTwithananaloguehasneverbeencomparedtocombinedmodality WereportaphaseIIIrandomisedtrialinlocallyadvancedPCa comparingacombinedmodalityandADTonly AUA 2010 内分泌治疗新进展 METHODSInthisFrenchmulticenter open randomisedtrial patientslessthan80years withhistologicallyconfirmedPCa T3 4 orpT3 biopsy N0M0wereincluded Theywerecentrallyrandomisedin2parallelgroupstoeitherADTalone leuprorelin11 25mgSR 1scinjectionevery3monthsfor3yearsorthesameADTcombinedwithRTstartingwithin3monthsover7weeks AUA 2010 内分泌治疗新进展 RESULTS AUA 2010 内分泌治疗新进展 Prevalenceofmetabolicsyndromeinprostatecancerpatientsunderandrogendeprivationtherapy interimresultsofacase controlstudy JorgeRopero Barcelone Spain AUA 2010 内分泌治疗新进展 INTRODUCTIONANDOBJECTIVESCardiovascularmortalityisthemostimportantcauseofdeathinpatientswithprostatecancer PC Thedevelopmentofmetabolicsyndrome MS inpatientsundergoingandrogendeprivationtherapy ADT hasbeenrelatedwiththisincreaseinmortalityrate TheaimofthisstudyhasbeentoconfirmthehypothesisthatADTincreasestheprevalenceofMS AUA 2010 内分泌治疗新进展 METHODSAgroupof157patientswereenrolledinthisinterimanalysisofaprospectivecasecontrolstudy 53PCpatientsunderADTduringameantimeof52months 6to252 and104agematchedcontrolsevaluatedatthetimeofprostatebiopsy 52withcancerand52without wereincluded AUA 2010 内分泌治疗新进展 METHODSMSwasanalyzedaccordingtheATPIIIpanelcriteria Fastingplasmaglucoselevel 110mg dLserumtriglyceridelevel 150mg dLserumhigh densitylipoproteinlevel102cmBloodpressureof 130 85mmHg 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 AUA 2010 内分泌治疗新进展 CONCLUSIONAlthoughthelimitednumbercasesandcontrolsincludedinthisinterimanalysis asignificantincreaseintheprevalenceofMSwasobservedinPCpatientssubjectedtoADT AUA 2010 内分泌治疗新进展 MetabolicchangeafterandrogendeprivationtherapyinKoreanmenwithprostatecancerChangHooPark Korea AUA 2010 内分泌治疗新进展 INTRODUCTIONANDOBJECTIVESInmenwithprostatecancer Androgendeprivationtherapyshowsavarietywellrecognizedmetabolicalteration TobettercharacterizethemetaboliceffectsofandrogendeprivationtherapyinKoreanmen weevaluatedthechangesinfatthickness bonemineraldensity BMD bodymassindex BMI andlevelsofhemoglobin Hb andcholesterol Wealsocomparedthemwithdatafromhealthysubjects AUA 2010 内分泌治疗新进展 METHODSFromDecember2002toDecember2008 148Koreanmentreatedwithleuprolidedepotandbicalutamideforprostatecancerand100healthysubjectswereinvestigatedincludedchangefrombaselinetomonth12infatthickness bonemineraldensity BMD bodymassindex BMI andlevelsofhemoglobin Hb andcholesterol AUA 2010 内分泌治疗新进展 RESULTS Therearenosignificantchangesinhemoglobinandcholesterollevels AUA 2010 内分泌治疗新进展 CONCLUSIONOurresultsshowthatKoreanmenwithprostatecancerhaveincreasedabdominalsubcutaneousfatandBMIandhavedecreasedBMDduringandrogendeprivationtherapy Theseincreasestheriskofbonefractureandcomplicationrelatedobesity Therefore BMDwillbecheckedperiodicallyandcarryoutexerciseprogramtopreventionobesityduringandrogendeprivationtherapy AUA 2010 内分泌治疗新进展 Sarcopeniainmenreceivingandrogendeprivationtherapyforprostatecancer aprospective3 yearstudy MatthewR Smith CA AUA 2010 内分泌治疗新进展 INTRODUCTIONANDOBJECTIVESAndrogendeprivationtherapy ADT forprostatecancerdecreasesbonemineraldensityandincreasesfracturerisk StudieswithlimitedsamplesizeandobservationalperiodshavereportedthatADTisalsoassociatedwithsarcopeniaorlossofmuscle leanbodymass LBM WenowreporttheprospectivechangesinLBMinasubsetofmenfromthatstudy AUA 2010 内分泌治疗新进展 METHODSMenundergoingADTfornonmetastaticprostatecancerat38centersinNorthAmericawererandomizedtodenosumaborplacebo Atotalof248subjects 130denosumab 118placebo withabaselineandwithatleast1on studyLBMresultwereconsideredevaluableandincludedinthisanalysis AUA 2010 内分泌治疗新进展 METHODSSubjectswerestratifiedatbaselinebyage 6months LBMwasmeasuredbytotalbodydual energyx rayabsorptiometryatbaselineandat12 24 and36months 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 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 AUA 2010 内分泌治疗新进展 CONCLUSIONThisisthelargestandlongestprospectivestudyundertakentodescribethenaturalhistoryofmusclelossinmenundergoingADTtherapyforprostatecancer LBMsignificantlydecreasedat12 24 and36months DecreasesinLBMweregreatestinoldermenandinthosewhohadshortdurationofADTatstudyentry AUA 2010 内分泌治疗新进展 RecoveryoftestosteroneandPSAaftercessationoflongtermluteinizinghormonereleasinghormoneagonist LHRH therapyforprostatecancer aprospectivetrial MatthewMcIntyre Charleston SC AUA 2010 内分泌治疗新进展 INTRODUCTIONANDOBJECTIVESTheuseofhormonalmanipulationinthetreatmentofprostatecancerhasbeenanoptionsincethetimeofHugginsinitialdescription However manyquestionsremainregardingtimingofinitiation andlengthoftreatmentintervalformedicallyinducedcastration AUA 2010 内分泌治疗新进展 INTRODUCTIONANDOBJECTIVESTheeffectsoflongtermLHRHagonistonthehypothymalicpituitarygonadalaxisarealsonotcompletelyunderstood WesoughttoexaminetheeffectsoflongtermLHRHagonistonrecoveryoftestosteroneandPSA AUA 2010 内分泌治疗新进展 METHODSHormonalablationwasdiscontinuedandserialtestosteroneandPSAmeasurementswereobtainedonathreemonthlybasis Patientswerecounseledregardingrestartinghormonaltherapyif2consecutiverisesinPSAwereobserved Patientswereallowedtostayoffhormonesandonstudyiftheydesired AUA 2010 内分泌治疗新进展 METHODSWeorganizedaprospectivetrialexaminingmenattheVeteransAdministrationHospitalwhohadbeenonatleast48monthsofanLHRHagonist OtherinclusioncriteriawerethatPSAbelessthan3ng ml andnotrisingforthe2consecutivevaluespriortodiscontinuinghormones AUA 2010 内分泌治疗新进展 RESULTSNineteenpatientswereenrolledinthestudybetween2007and2008 Themeanagewas75years Themeandurationofhormonaltherapywas88months AUA 2010 内分泌治疗新进展 RESULTSTen 53 patientswereonhormonesforbiochemicalrecurrence Two 10 formetastaticdisease Seven 36 asprimarytherapy AUA 2010 内分泌治疗新进展 RESULTSEleven 58 patientshad2consecutiverisesinPSA Themeantimetoseetwoconsecutiveriseswas11months 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 AUA 2010 内分泌治疗新进展 RESULTSTwelve 63 patientshadrecoveryoftestosteroneabove50ng dl Four 21 patientsremainedcastrateofftherapyameanof20months Themeantimetotestosteronerecoverywas12 8months Two 10 5 patientsinthestudyhavedied Onedeathwasattributedtoprostatecancer AUA 2010 内分泌治疗新进展 CONCLUSIONTherecoveryoftestosteroneandsignificantelevationsofPSAafterlongtermLHRHagonisttherapyissignificantlydelayedinmostpatients Thishelpstosupporttheconceptofintermittentandrogenablationwhichh