1FranklySpeakingAboutLungCancer“WhatYouNeedtoKnowAboutLungCancer&ItsTreatment〞

2FranklySpeakingAboutLungCancerPowerfulfacts:177,000casesannuallyLungcanceristhe#1causeofcancer-relateddeathsbyfarintheU.S. …morethanbreast,prostate,andcoloncancercombined. 3FranklySpeakingAboutLungCancerRiskFactors:Smoking(90%ofallcases)Second-handsmoke(25%ofnon-smokercases)Occupational/environmental

4FranklySpeakingAboutLungCancerNon-SmallCellLungCancer(NSCLC)Comprises

85%ofalllungcancersTypesofNSCLC:Adenocarcinoma(mostcommon)SquamouscellBronchoalveolarCarcinomaLargeCellCarcinomaAdenosquamous5FranklySpeakingAboutLungCancer SmallCellLungCancer(SCLC)Comprises

15-20%ofalllungcancersSpreadsmoreaggressivelythanNSCLCIsmoreresponsivetochemotherapyFrequentlyfoundinsmokersorformersmokers6FranklySpeakingAboutLungCancerStagesofNon-SmallCellLungCancerStageI confinedtolungtissuealoneStageII lungtissueandlymphnodesin lungStageIII lungtissueandlymphnodes outsideofthelungStageIV distantspread(liver,adrenal glands,bone,brain,othersites)7FranklySpeakingAboutLungCancer

LUNGCANCERSTAGING(TNM) T=Primarytumorsize(T1-T4) N=Lymphnodeinvolvement(N1-N3) M=Distantmetastasis(M0-M1)

8FranklySpeakingAboutLungCancerTreatmentofStageINSCLCEvaluateforsurgerySurgeryaloneisthestandardofcarePathologicstageI:67%cureClinicaltrialsareevaluatingthevalueofadjuvant(aftersurgery)therapy9FranklySpeakingAboutLungCancerTreatmentofStageIINSCLCEvaluatefortypeofsurgerySurgeryaloneisthestandardofcarePathologicstageII:40-50%cureClinicaltrialsareevaluatingthevalueofadjuvant(aftersurgery)therapy10FranklySpeakingAboutLungCancer‘Theoretical’AdvantagesofCombiningDifferentTypesofCancerTherapiesChemotherapy: Controlsmicro-metastasesthatmayberesponsibleforsystemicrecurrenceafter“successful〞surgery ActssynergisticallywithXRTtodownstageNSCLCandmaketumor-freemarginsurgerymorelikelyRadiationTherapy “Sterilizes〞surgicalmarginsmakinglocalrecurrencelesslikely

11FranklySpeakingAboutLungCancerSummary:TreatmentStageI&IINSCLCSurgeryisthestandardofcareNeoadjuvant(givenbeforesurgery)therapyispromisingAdjuvant(givenaftersurgery)chemotherapyorradiationtherapyshownoimprovement12FranklySpeakingAboutLungCancerStageIIINon-SmallCellLungCancer2types:StageIIIAandStageIIIBRadiationalonewasthestandardcareuntil1990’sChemotherapy+radiationisthenewstandardbasedonresultsofclinicaltrialsNewerradiationtechniquesminimizesideeffectsoftreatment

13FranklySpeakingAboutLungCancerTreatmentofStageIIINSCLCChemo+radiation=standardofcareRoleofsurgeryisundefinedUnansweredquestions:-Whichchemoisbest?Howdoesonedecide?-When&howshouldchemotherapybegiven?-When&howshouldradiationbegiven?14FranklySpeakingAboutLungCancerStageIIIANon-SmallCellLungCancerBulkyvs.minimaldiseaseChemotherapy+radiationCommonlyusedchemotherapydrugs:Platinum-basedNon-platinumbasedRoleofsurgeryundefined15FranklySpeakingAboutLungCancerStageIIIBNon-SmallCellLungCancerPleuraleffusionaffectstreatmentplanChemotherapy+radiationorradiationaloneCommonlyusedchemotherapydrugs:Platinum-basedNon-platinumbased

16FranklySpeakingAboutLungCancerTreatmentofStageIIIB-IVNSCLCReduceChemotherapyToxicityRecentstudy:Combinationof2drugsprovidesamebenefitas3,butwithfewersideeffects:Lessnausea/vomitingLesshairlossLessnervedamageLowerriskofinfectionGemcitabine+vinorelbineslightlylesstoxicitybutequivalentresponse(Cancer,Vol.95,No.6,2002)17FranklySpeakingAboutLungCancerStageIVNSCLC

NCIRecommendedFirst-LineChemotherapy:gemcitabine+cisplatinpaclitaxel+carboplatinorcisplatinvinorelbine+cisplatindocetaxel+cisplatinOtherdrugcombinations

18FranklySpeakingAboutLungCancerTreatmentofRecurrentNSCLCChallengesofdecision-makingGeneralhealthstatusofthepatientSeveraltreatmentoptionswithequivalentresultsbutwidelyvaryingsideeffectsBalancingqualityoflifewithsideeffectsPatient’sgoalsandwishes

19TreatmentofSmallCellLungCancerLimitedstage:chemo+xrt=standardofcareetoposide+cisplatin+radiationcisplatin+irinotecanExtensivestage:first-linechemotherapyetoposide(VP-16)+cisplatin(orcarboplatin)+ radiationcisplatin+irinotecanCAV,CAEinclinicaltrials20TreatmentofRecurrentSmallCellLungCancerPossibleChemotherapyAgents:topotecan(Hycamtin):onlyFDA-approveddrugforrecurrentdiseaseoraletoposide(VP-16)paclitaxel(Taxol)irinotecan/CPT-11(Camptosar)CAVothersinclinicaltrialsPalliativeradiationtorelievesymptoms21NewerStrategies:TargetedTherapyChemotherapytargetsgeneralfeaturesofcells,includingbothcancercellsandnormalcellsNormalcellsusuallyrecover,whilecancercellsmaynotHowever,chemotherapyisassociatedwithsideeffects22EpidermalGrowthFactorReceptorsAngiogenesisAntisenseProteinKinaseCC-kitPDGF-rCox-2RasinhibitorsRafinhibitorsMapkinaseOthersExamplesofLungCancerTargetedTherapyinDevelopment23FranklySpeakingAboutLungCancerEpidermalGrowthFactorReceptors

Iressa(AstraZeneca)Tarceva(Genentech)Erbitux(Imclone,BMS)Manyothersindevelopment24FranklySpeakingAboutLungCancerAngiogenesisInhibitors“Angio〞=bloodvessel,“Genesis〞=formationorbeginningManyagentsbeingtestedtoinhibitthisprocess:Anti-VEGFThalidomideAngiostatin/EndostatinAnti-VEGFtyrosinekinaseinhibitorsOthers 25FranklySpeakingAboutLungCancerAntisenseDrugsAffinitac(Lilly)AntisensedrugtoproteinkinaseCPhaseIIstudiescompletedcombiningwithchemotherapyEvaluatingeffectivenessinrecurrentlungcancerPhaseIIItrialsunderwaycomparingchemotherapy+drug

26FranklySpeakingAboutLungCancer“WhatYouNeedtoKnowAboutLungCancer&ItsTreatment〞 QuestionsandDiscussion27FranklySpeakingAboutLungCancer

PATIENTACTIVEBREAK28FranklySpeakingAboutLungCancer“IssuestoDiscussWithYourDoctorWhenMakingDecisionsAboutLungCancerTreatment:APatientActiveApproach〞29FranklySpeakingAboutLungCancerMakingdecisionsaboutcancertreatmentisacomplexandsometimesoverwhelmingexperience.Youhavechoices.Butyouneedtobeinformed&youneedtoevaluatemanyaspectsofyourcare.30FranklySpeakingAboutLungCancerWhatisthegoalofmycancertherapy?Isitprolongationoflife?Istocontrolsymptoms?Isitpalliation?31FranklySpeakingAboutLungCancerWhatisaclinicaltrialandwouldonebeareasonabletreatmentoptionforme?Whataretherisksandbenefits?32FranklySpeakingAboutLu