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1、NewTherapeuticStrategyofHormoneRefractoryProstateCancer(HRPC)MingLIU,GangZHU,BenWAN,JianyeWANG2007-7-12Beijing,ChinaDefinitionandCategoryofHRPC1.Definition!!Androgen-independentbuthormone-sensitivePcashouldbeexcluded.“CUAguidelinesforPca(2007)”2.CategoryBiochemicalonlydisease;Asymptomaticdi
2、seasewithpositivescans;Symptomaticdisease.TherapeuticoptionsforandrogenindependentPcaAndrogendeprivation(24-36months)Continueandrogendeprivation(modestpotentialbenefitvsminimalrisk)Non-steroidalanti-androgens(bicalutamide/flutamide)(60-80%,4-6months)Substitutionofflutamidewithhigh-dosebical
3、utamide(25-40%,4-6months)Anti-androgenwithdraw(30-40%,5-6months)SecondaryhormonaltherapyKetoconazole/corticosteriodDESPalliativetherapeuticoptions(externalbeamradiation,radionuclide,bisphosphonates,etc)Chemotherapy??Source:“EUAguidelinesforPca(2007)”HistoryofchemotherapyforHRPCPre-taxaneera
4、prePSAera（before1990s)“HRPCisnoresponsivetochemotherapy”PSAera(Mitoxantrone/Estramustine)“ChemotherapycoulddecreasePSA,reliefpainandimprovequalityoflife,butneithercoulddemonstrateimprovementofsurvival”SideeffectTaxaneeraDocetaxel1.Stabilizingmicrotubule.ArrestincellproliferationinG2-Mphase2
5、.Inactivatingantiapoptosismechanismbyinhibitbcl-2andbcl-xlSource:EuropeanUrology51(2007)17-26TAX327–experimentdesignTAX3271006casesofmetastaticHRPCpatientsMedianfollow-upof20.7~20.8months“Phase3trial(randomized,controlled,noneblinded,multicenter)”Mitoxantrone12mg/m2(day1)+prednisone5mgBid21
6、-daycyclesDocetaxel75mg/m2(day1)+prednisone5mgBid21-daycyclesDocetaxel30mg/m2+prednisone5mgBidweeklySource:NEnglJMed351;15october7,2004TAX327–keyfindingsBetterPSAresponse(13%better)Morepainrelief(13%better)Betterqualityoflife(9%better)Improvementinmediansurvival(2.4monthslonger)Reductionofr
7、iskofdeath(0.24lower)337335334HRO.76(0.01)O.76(0.01)Docetzxel/EMPMitoxatroneQOL22%13%23%HR:hazardratiofordeath“Docetaxel3-weekgroupisthebest”Source:NEnglJMed351;15october7,2004ComparingwithMitoxantrone,Docetaxel3-weekregimenisbetterbecause:SWOG9916337335
