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1、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AUA(2010)内分泌治疗新进展Radiotherapy combined with androgen deprivation vs. androgen deprivation alone in clinically locally advanced prostate caner in a multicenter randomised phase III studyNicolasMottet,France.抑那通治疗前列腺癌的新进展AUA(2010)内分泌治疗新进展INTRODUCTIONANDOBJECTIVESInlocallyadva
2、nceddisease,thecombinationofradiotherapy(RT)andandrogendeprivation(ADT)issuperiortoRTalone.ButADTwithananaloguehasneverbeencomparedtocombinedmodality.WereportaphaseIIIrandomisedtrialinlocallyadvancedPCa,comparingacombinedmodalityandADTonly.抑那通治疗前列腺癌的新进展AUA(2010)内分泌治疗新进展METHODSInthisFrenchmulticenter
3、,open,randomisedtrial,patientslessthan80years,withhistologicallyconfirmedPCa,T3-4,orpT3(biopsy)N0M0wereincluded.Theywerecentrallyrandomisedin2parallelgroupstoeitherADTalone(leuprorelin11.25mgSR,1scinjectionevery3monthsfor3yearsorthesameADTcombinedwithRTstartingwithin3monthsover7weeks.抑那通治疗前列腺癌的新进展AU
4、A(2010)内分泌治疗新进展RESULTSHTHTHT+RTHT+RTP PN131133MeanAge70.570.70.63MeanPSAbaseline51.7741.500.79MedianPFS(days)126425440.0005PFS(5year)(%)15.464.70.0005Biologicalprogression(%)71.519.50.0001Clinicalprogression(%)37.711.3110mg/dLserumtriglyceridelevel150mg/dLserumhigh-densitylipoproteinlevel102cmBloodp
5、ressureof130/85mmHg.抑那通治疗前列腺癌的新进展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.抑那通治疗前列腺癌的新进展AUA(2010)内分泌治疗新进展CONCLU
6、SIONAlthoughthelimitednumbercasesandcontrolsincludedinthisinterimanalysis,asignificantincreaseintheprevalenceofMSwasobservedinPCpatientssubjectedtoADT.抑那通治疗前列腺癌的新进展AUA(2010)内分泌治疗新进展MetabolicchangeafterandrogendeprivationtherapyinKoreanmenwithprostatecancerChangHooPark,Korea抑那通治疗前列腺癌的新进展AUA(2010)内分泌治
7、疗新进展INTRODUCTIONANDOBJECTIVESInmenwithprostatecancer,Androgendeprivationtherapyshowsavarietywellrecognizedmetabolicalteration.TobettercharacterizethemetaboliceffectsofandrogendeprivationtherapyinKoreanmen,weevaluatedthechangesinfatthickness,bonemineraldensity(BMD),bodymassindex(BMI),andlevelsofhemog
8、lobin(Hb)andcholesterol.Wealsocomparedthemwithdatafromhealthysubjects.抑那通治疗前列腺癌的新进展AUA(2010)内分泌治疗新进展METHODSFromDecember2002toDecember2008,148Koreanmentreatedwithleuprolidedepotandbicalutamideforprostatecancerand100healthysubjectswereinvestigatedincludedchangefrombaselinetomonth12infatthickness,bonem
9、ineraldensity(BMD),bodymassindex(BMI),andlevelsofhemoglobin(Hb)andcholesterol.抑那通治疗前列腺癌的新进展AUA(2010)内分泌治疗新进展RESULTSADTADTControlControlP PN148100Fatthickness(mm)20.416.90.05BMD=bonemineraldensity0.910.940.05BMI(kg/m2)23.922.90.05Therearenosignificantchangesinhemoglobinandcholesterollevels.抑那通治疗前列腺癌的
10、新进展AUA(2010)内分泌治疗新进展CONCLUSIONOurresultsshowthatKoreanmenwithprostatecancerhaveincreasedabdominalsubcutaneousfatandBMIandhavedecreasedBMDduringandrogendeprivationtherapy.Theseincreasestheriskofbonefractureandcomplicationrelatedobesity.Therefore,BMDwillbecheckedperiodicallyandcarryoutexerciseprogramt
11、opreventionobesityduringandrogendeprivationtherapy.抑那通治疗前列腺癌的新进展AUA(2010)内分泌治疗新进展Sarcopenia in men receiving androgen deprivation therapy for prostate cancer: a prospective 3-year study.MatthewR.Smith,CA.抑那通治疗前列腺癌的新进展AUA(2010)内分泌治疗新进展INTRODUCTIONANDOBJECTIVESAndrogendeprivationtherapy(ADT)forprostat
12、ecancerdecreasesbonemineraldensityandincreasesfracturerisk.StudieswithlimitedsamplesizeandobservationalperiodshavereportedthatADTisalsoassociatedwithsarcopeniaorlossofmuscle(leanbodymass,LBM).WenowreporttheprospectivechangesinLBMinasubsetofmenfromthatstudy.抑那通治疗前列腺癌的新进展AUA(2010)内分泌治疗新进展METHODSMenund
13、ergoingADTfornonmetastaticprostatecancerat38centersinNorthAmericawererandomizedtodenosumaborplacebo.Atotalof248subjects(130denosumab,118placebo)withabaselineandwithatleast1on-studyLBMresultwereconsideredevaluableandincludedinthisanalysis.抑那通治疗前列腺癌的新进展AUA(2010)内分泌治疗新进展METHODSSubjectswerestratifiedatb
14、aselinebyage(6months).LBMwasmeasuredbytotalbodydual-energyx-rayabsorptiometryatbaselineandat12,24,and36months.抑那通治疗前列腺癌的新进展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)
15、.抑那通治疗前列腺癌的新进展AUA(2010)内分泌治疗新进展RESULTSMenaged70years(n=127)hadsignificantlygreaterchangesinLBMatallmeasuredtimepoints.At36months,LBMdecreasedby2.8%inmenaged70yearscomparedwithadecreaseof0.9%inyoungermen(p=0.035).抑那通治疗前列腺癌的新进展AUA(2010)内分泌治疗新进展CONCLUSIONThisisthelargestandlongestprospectivestudyundert
16、akentodescribethenaturalhistoryofmusclelossinmenundergoingADTtherapyforprostatecancer.LBMsignificantlydecreasedat12,24,and36months.DecreasesinLBMweregreatestinoldermenandinthosewhohadshortdurationofADTatstudyentry.抑那通治疗前列腺癌的新进展AUA(2010)内分泌治疗新进展RecoveryoftestosteroneandPSAaftercessationoflongtermlute
17、inizinghormonereleasinghormoneagonist(LHRH)therapyforprostatecancer:aprospectivetrial.MatthewMcIntyre,Charleston,SC抑那通治疗前列腺癌的新进展AUA(2010)内分泌治疗新进展INTRODUCTIONANDOBJECTIVESTheuseofhormonalmanipulationinthetreatmentofprostatecancerhasbeenanoptionsincethetimeofHugginsinitialdescription.However,manyquest
18、ionsremainregardingtimingofinitiation,andlengthoftreatmentintervalformedicallyinducedcastration.抑那通治疗前列腺癌的新进展AUA(2010)内分泌治疗新进展INTRODUCTIONANDOBJECTIVESTheeffectsoflongtermLHRHagonistonthehypothymalicpituitarygonadalaxisarealsonotcompletelyunderstood.WesoughttoexaminetheeffectsoflongtermLHRHagoniston
19、recoveryoftestosteroneandPSA.抑那通治疗前列腺癌的新进展AUA(2010)内分泌治疗新进展METHODSHormonalablationwasdiscontinuedandserialtestosteroneandPSAmeasurementswereobtainedonathreemonthlybasis.Patientswerecounseledregardingrestartinghormonaltherapyif2consecutiverisesinPSAwereobserved.Patientswereallowedtostayoffhormonesand
20、onstudyiftheydesired.抑那通治疗前列腺癌的新进展AUA(2010)内分泌治疗新进展METHODSWeorganizedaprospectivetrialexaminingmenattheVeteransAdministrationHospitalwhohadbeenonatleast48monthsofanLHRHagonist.OtherinclusioncriteriawerethatPSAbelessthan3ng/ml,andnotrisingforthe2consecutivevaluespriortodiscontinuinghormones.抑那通治疗前列腺癌
21、的新进展AUA(2010)内分泌治疗新进展RESULTSNineteenpatientswereenrolledinthestudybetween2007and2008.Themeanagewas75years.Themeandurationofhormonaltherapywas88months.抑那通治疗前列腺癌的新进展AUA(2010)内分泌治疗新进展RESULTSTen(53%)patientswereonhormonesforbiochemicalrecurrence；Two(10%)formetastaticdisease；Seven(36%)asprimarytherapy.抑那
22、通治疗前列腺癌的新进展AUA(2010)内分泌治疗新进展RESULTSEleven(58%)patientshad2consecutiverisesinPSA;Themeantimetoseetwoconsecutiveriseswas11months.抑那通治疗前列腺癌的新进展AUA(2010)内分泌治疗新进展RESULTSThemeantimeofftherapypriortoariseinPSA0.1ng/mlabovebaselineforallpatientsandthosewith2consecutiveriseswas15.4and9.5monthsrespectively.Th
23、emeanbaselinePSA,meanPSAatone,andattwoyearsofftherapywas0.3ng/ml,1.1ng/ml,and5ng/mlrespectively.Meantestosteroneatbaseline,one,andtwoyearsofftherapywas13.9ng/ml,76ng/ml,and150.6ng/mlrespectively.抑那通治疗前列腺癌的新进展AUA(2010)内分泌治疗新进展RESULTSTwelve(63%)patientshadrecoveryoftestosteroneabove50ng/dl.Four(21%)pa
24、tientsremainedcastrateofftherapyameanof20months.Themeantimetotestosteronerecoverywas12.8months.Two(10.5%)patientsinthestudyhavedied.Onedeathwasattributedtoprostatecancer.抑那通治疗前列腺癌的新进展AUA(2010)内分泌治疗新进展CONCLUSIONTherecoveryoftestosteroneandsignificantelevationsofPSAafterlongtermLHRHagonisttherapyissig
25、nificantlydelayedinmostpatients.Thishelpstosupporttheconceptofintermittentandrogenablationwhichhasbenefitsinqualityoflifeandreducedcostoftherapy.抑那通治疗前列腺癌的新进展Dataonfile手术去势的副作用手术去势的副作用增加心血管疾病和糖尿病发病率增加心血管疾病和糖尿病发病率抑那通治疗前列腺癌的新进展Dataonfile手术去势的副作用手术去势的副作用增加骨折发病率增加骨折发病率抑那通治疗前列腺癌的新进展抑那通通过抑制雄性激素的作用而抑制大白鼠前列
26、腺肿瘤的增殖 醋酸亮丙瑞林水溶液0.333mg/kg/日（1日1次投药)醋酸亮丙瑞林水溶液0.333mg/kg/日（1日2次投药)抑那通相当于0.333mg/kg/日（1月1次投药)阉割肿瘤移植后的天数肿瘤移植后的天数肿肿 瘤瘤 体体 积积(cm)对照醋酸亮丙瑞林水溶液1mg/kg/日（1日1次投药)抑那通与睾丸切除术抗肿瘤作用比较抑那通与睾丸切除术抗肿瘤作用比较抑那通治疗前列腺癌的新进展抑那通治疗前列腺癌的综合效果抑那通治疗前列腺癌的综合效果抑那通治疗前列腺癌的新进展抑那通治疗前列腺癌各病灶的疗效抑那通治疗前列腺癌各病灶的疗效抑那通治疗前列腺癌的新进展抑那通改善前列腺癌各种症状的效果明显抑那
27、通改善前列腺癌各种症状的效果明显抑那通治疗前列腺癌的新进展抑那通治疗前列腺癌从起效到部分缓解的时间抑那通治疗前列腺癌从起效到部分缓解的时间抑那通治疗前列腺癌的新进展 间歇疗法与持续疗法患者生存率相当间歇疗法与持续疗法患者生存率相当Dataonfile抑那通治疗前列腺癌的新进展抑那通间歇疗法显著降低前列腺体积抑那通间歇疗法显著降低前列腺体积第1周期第2周期前列腺体积变化比例(%)BruchovskyN,etal.Cancer.2006Jul15;107(2):389-95抑那通治疗前列腺癌的新进展抑那通间歇疗法迅速降低抑那通间歇疗法迅速降低PSAPSA值值到达PSA最低值所需时间(月)Higan
28、oCS,etal.Urology.1996Nov;48(5):800-4抑那通治疗前列腺癌的新进展间歇疗法减少骨质丢失，降低副反应发生率间歇疗法减少骨质丢失，降低副反应发生率UifTunn2007BjuInternational99,supplement1,19-22抑那通治疗前列腺癌的新进展Dataonfile间歇期雄激素明显恢复，可改善患者生活质量间歇期雄激素明显恢复，可改善患者生活质量间歇期雄激素明显恢复，可改善患者生活质量间歇期雄激素明显恢复，可改善患者生活质量抑那通治疗前列腺癌的新进展间歇疗法有利于患者性功能恢复间歇疗法有利于患者性功能恢复N.A.Spry,etalEuropeanJ
29、ournalofCancer42(2006):1083-1092抑那通治疗前列腺癌的新进展间歇期暂停用药，大幅度降低治疗成本间歇期暂停用药，大幅度降低治疗成本抑那通治疗前列腺癌的新进展总总 结结 有效治疗前列腺癌有效治疗前列腺癌有效治疗前列腺癌有效治疗前列腺癌 患者生存率与持续疗法相当患者生存率与持续疗法相当患者生存率与持续疗法相当患者生存率与持续疗法相当 与去势疗法相比，副作用显著降低与去势疗法相比，副作用显著降低与去势疗法相比，副作用显著降低与去势疗法相比，副作用显著降低 改善性功能，提高生活质量改善性功能，提高生活质量改善性功能，提高生活质量改善性功能，提高生活质量 降低治疗成本降低治疗成本降低治疗成本降低治疗成本抑那通间歇疗法优势突出抑那通间歇疗法优势突出抑那通间歇疗法优势突出抑那通间歇疗法优势突出抑那通治疗前列腺癌的新进展抑那通3.75mg预充式注射器现有剂型现有剂型上市新剂型上市新剂型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
