肺癌的生物靶向治疗进展

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1、肺癌的生物靶向治疗进展上海市肺科医院肿瘤科CurrentAnti-CancerApproachesSurgeryChemo-therapyRadiationHormonaltherapyTargetedtherapyRemoveknowntumormassesKillrapidlydividingtumorcells,includingtumorcellsinadjacenttissuesKillrapidlydividingtumorcellsInhibitthegrowthandsurvivalofhormone-dependentt

2、umorcellsSpecificallyinhibitprocessesrequiredfortumorcellgrowthWhydoweneednewanticanceragents?*1-yearsurvivalrateDatafromtheEUROCAREIIstudy80706050403020100Relative5-yearsurvivalrate(%)BreastColonKidneyLiverLung*OvaryPancreas1978–19801984–19861987–1989Whatmakesanidealthe

3、rapeutictarget?PresentinthemajorityofpatientswithspecifictumortypeCausativelinkwithtumourigenesisEssentialfunctionintumorcellsAssessingnoveltargetedagentsTypicalcytotoxicMTDOBDToxicityAntitumoureffectEffectTargetDoseOBD>MTDAdaptedfromRowinsky2000TargetToxicityAntitumoureff

4、ectOBDMTDEffectOBD

5、altherapyresistancepooroutcomeEGFRhighlyexpressedinNSCLCExtensiveclinicalexperiencewithgefitinibMonotherapyIDEAL1IDEAL25PhaseItrialsCombinationtherapyINTACT1INTACT2ExpandedAccessProgrammePost-marketinguseinJapanOthersalesOtherNSCLCstudiesTrialsinothertumourtypesn2092162707

6、20684~39,200~39,100~9100~6002600TOTAL~92,750Dataasof3Sept2003IDEAL,IRESSADoseEvaluationinAdvancedLungcancerINTACT,IRESSANSCLCTrialAssessingCombinationTreatmentRandomisationGefitinib250mgoncedailyGefitinib500mgoncedailyPatientsAdvancedNSCLChavingreceived1or2(IDEAL1)or>2(I

7、DEAL2)previouschemotherapyregimensContinuegefitinibuntildiseaseprogressionorunacceptabletoxicityPrimaryendpointsResponserate(bothtrials)Safetyprofile(IDEAL1)Symptomrelief(IDEAL2)IDEAL1:platinum,1or2priorregimens(n=209)IDEAL2:platinumanddocetaxel,>2priorregimens(n=216)G

8、efitinibPhaseIIstudies:IDEAL1&2Tumourresponse:IDEAL1&2(250mg/day)Objectiveresponserate=