《EGFR靶向治疗癌症》

CurrentstatusofEGFR-targetedcancertherapyS,Surgery;RT,Radiotherapy;

CT,Chemotherapy/hormonetherapy

EGFR,epidermalgrowthfactorreceptorPre-

malignancyLocalizedtumorsLocally/

regionallyadvanced

diseaseAdvanced/metastaticdiseaseSRTCT+RTCTEGFR-targetedtherapyPotentialtreatmentoptionsfor

EGFR-targetedtherapiesTheconceptTargetedtherapyforabroad

rangeofcommonsolidtumors(includinglung,breast,prostate,colon,ovarian,andgastric)ClinicaltrialsProofofconceptwell-toleratedtherapytumorresponsesinseveraltumortypesThepotentialImprovedoutcomesinthetreatmentofcommonsolidtumorsFromconcepttoclinicaltrialsTumorresponsemAbsTKIsKKKmAbs,monoclonalantibodies;TKIs,tyrosinekinaseinhibitorsClinicaldevelopmentof

anticanceragentsTypicalcytotoxic

OBD>MTDMTDOBD

ToxicityAntitumoreffectEffectTargetDoseOBDMTDNoveltargetedagents

OBD<MTDOBD,optimalbiologicdose;MTD,maximumtolerateddose

Rowinsky2000DoseEffectTargetAntitumoreffect

ToxicityClinicaldevelopmentof

EGFR-targetedtherapiesPhaseItrialsfailedtoidentifytheMTDofcetuximab;theOBDwasidentifiedasthedosethatsaturatedtheantibodysystemicclearancerate

(200mg/m2/week)Gefitinib(IRESSA)PhaseItrialsdididentifythe

MTD(700-1000mg/day),butalsoshowedthattheOBDwas250mg/day,asconfirmedinPhaseIItrialsPhaseItrialsoferlotinibidentifiedtheMTDas

150mg/day;thisistherecommendeddoseBaselgaetal2000;Baselgaetal2002;Herbstetal2002;

Nakagawaetal2003;Ransonetal2002;Fukuokaetal2003;

Krisetal2003;Hidalgoetal2001Cetuximab:approvedforthetreatmentofadvanced

colorectalcancer

Partialresponserate,%Diseasecontrolrate,%MedianTTP,monthsMediansurvival,monthsCombination*

(n=218)22.955.54.18.6Monotherapy

(n=111)10.832.41.56.9pvalue

0.0070.001<0.0010.48*Cetuximabincombinationwithirinotecan

TTP,timetoprogressionCunninghametal2003Gefitinib(250mg/day):approvedfor

thetreatmentofadvancedNSCLC

Responserate,%Diseasecontrolrate,%Mediansurvival,months1-yearsurvival,%Symptomimprovement*,%IDEAL1

(n=103)18.454.47.63540.3IDEAL2

(n=102)11.842.26.52743.1*Assessedin67symptomaticpatientsinIDEAL1and102symptomaticpatientsinIDEAL2Fukuokaetal2003;Krisetal2003Erlotinib:awaitingapproval

forthetreatmentof

advancedNSCLC

Responserate,%Diseasecontrolrate,%Mediansurvival,months1-yearsurvival,%

n=5712.350.98.440Perez-Soleretal2003OtherEGFR-targetedtherapies

underclinicaldevelopmentKKKEMD72000h-R3ABX-EGFPKI-1066CI-1033EKB-569mAbsTKIsSummaryofcurrent

EGFR-targetedtreatmentoptionsTodate,twoEGFR-targetedtherapieshavebeenapprovedforthetreatmentofpatientswithadvancedormetastaticCRC(cetuximab)orNSCLC(gefitinib)ApprovaloferlotinibforthetreatmentofadvancedNSCLCise