化療引起的惡心嘔吐的預(yù)防與管理

化療引起的惡心嘔吐的預(yù)防與管理第1頁/共90頁PatientPerceptionsoftheMostSevereSideEffectsofCancerChemotherapyRank198311993219953199941.VomitingNauseaNauseaNausea2.NauseaConstantlytiredLossofhairLossofhair3.LossofhairLossofhairVomitingConstantlytired

4.ThoughtofcomingfortreatmentEffectonfamilyConstantlytiredVomiting5.LengthoftimetreatmenttakesVomitingHavingtohaveaninjectionChangesinthewaythingstasteAdaptedfrom:1CoatesAetal.EurJCancerClinOncol.1983;19:203-8.2GriffinAMetal.AnnOncol.1996;7:189-95.3DeBoer-DennertMetal.BrJCancer.1997;76:1055-61.4LindleyCetal.CancerPract1999;7:59-65.第2頁/共90頁CINV-DefinitionsAcute–withinafewminutestoseveralhoursafterdrugadministrationandcommonlyresolveswithin24hours.Delayed–developsinpatientsmorethan24hoursafterchemotherapyadministration.Maylastupto6daysItcommonlyoccurswithcisplatin,carboplatin,cyclophosphamideand/oranthracyclines.Anticipatory–nauseaand/orvomitingbeforepatientsreceivetheirchemotherapy,afterapriornegativeexperiencewithchemotherapyBreakthrough–occursdespiteprophylactictreatmentand/orrequiresrescue.Refractory–nauseaandemesisduringsubsequentcycleswhenantiemeticprophylaxisand/orrescuehavefailedinearliercyclesAdaptedfrom:ASHPAmJHealthSystPharm1999;56:729-764NCCNPracticeGuidelinesinOncology–Version3.2008.Antiemesis第3頁/共90頁RatesofCINVAdaptedfrom:1.HickokJT,etal.Cancer.2003;97:2880-6.2./previous_meetings/mcm_2005/cemornings2005/CEM_CINV_handout.pdf第4頁/共90頁Chemotherapy-InducedEmesis

RiskFactorsPatient-relatedriskfactorsinclude:YoungerageFemalegenderNo/minimalpriorhistoryofalcoholusePriorCINVAnxietyHighpretreatmentexpectationofseverenauseaAdaptedfrom:GregoryREetal.Drugs.1998.;2.HeskethPJetal.JClinOncol.1997.RoscoeJA,BushunnowP,MorrowGR,etal.Patientexperienceisastrongpredictorofseverenauseaafterchemotherapy:aUniversityofRochesterCommunityClinicalOncologyProgramstudyofpatientswithbreastcarcinoma.Cancer2004;101:2701-2708第5頁/共90頁InfluenceofPatientExpectationsonCINVExpectancyofnauseaassessedbeforepatientsreceivedtheirfirstdoxorubicin-basedchemotherapytreatmentwasfoundtobeastrongpredictorofsubsequentnausea.AdaptedfromRoscoeetal.Cancer.2004101(11):2701-8.第6頁/共90頁Chemotherapy-InducedEmesisRiskFactorsTreatment-relatedriskfactorsinclude:HighdrugdoseHighemetogenicityofchemotherapydrugsOfalltheknownpredictivefactors,theemetogenicityofagivenchemotherapeuticagentisthepredominantfactor.AdaptedfromASHPAmJHealthSystPharm1999;56:729-64.第7頁/共90頁CausesofCINVInadditiontoemesisinducedbychemotherapy,CINVcanbecausedby:PartialorcompletebowelobstructionVestibularDysfunctionBrainMetastasesElectrolyteimbalance:hypercalcemia,hyperglycemia,hyponatremia,uremiaConcomitantdrugs,includingopiatesGastroparesisinducedbyatumororchemotherapy(suchasvincristine)Psychophysiologicfactors,includinganxietyaswellasanticipatorynauseaandvomitingAdaptedfromNCCNPracticeGuidelinesinOncology–Version3.2008.Antiemesis.第8頁/共90頁ConsequenceofUnresolvedCINVDiscontinuationoftherapySeriousmetabolicderangementsNutritionaldepletionandanorexiaEsophagealtearsWounddehiscenceDeteriorationofpatients’physicalandmentalstatusDegenerationofself-careandfunctionalabilityAdversesequelaeofnauseaandvomitinginthecancerpatient.AdaptedfromNCCNPracticeGuidelinesinOncology–Version3.2008.Antiemesis.第9頁/共90頁Polloftheaudience

AsHealthcareprofessionalsweoften:

A.AccuratelyrecognizetheincidenceofacuteanddelayedCINVinourownpractices.B.UnderestimatetheincidenceofacuteanddelayedCINVinourownpractices.第10頁/共90頁AntiNauseaChemotherapyRegistry(ANCHOR)studyTheauthorsdeterminedtheincidenceofacuteanddelayedCINVaftermodernantiemetics.ThentheycomparedtheactualincidencesofCINVtothepredictionsmadebyphysiciansandnursesregardingthesepatients.AdaptedfromGrunbergSMetal.Cancer2004;100:2261-8.第11頁/共90頁AnchorStudyPerceptionvsReality

ModeratelyEmetogenicChemotherapyAdaptedfromGrunbergetal.Cancer2004;100:2261-8.第12頁/共90頁ToxicityAssessmentsGradecommontoxicityeffectsofadjuvantbreastcancerpatients.Patientsareassessedthedayofchemotherapyandagain2-3dayspostchemotherapy.Patientsalsohaveanumbertocallbackiftheyexperienceanytoxicities.Dr.H.BlissMurphyCancerCenter,

St.John’sNewfoundland第13頁/共90頁RatesofCINVinN=26Dr.H.BlissMurphyCancerCenter,

St.John’sNewfoundland第14頁/共90頁RateofCINVAdaptedfromCancer2004;100:2261-8.N=231attheDr.H.BlissMurphyCancerCenter,St.John’sNewfoundlandincomparisontotheGrunbergdata第15頁/共90頁HealthCareProfessionalsPerceptionofCINV

attheDr.H.BlissMurphyCancerCenter,

St.John’sNewfoundlandAdaptedfromCancer2004;100:2261-8.第16頁/共90頁CINV—DecreasedQualityofLifeCINVadverselyimpactpatients'qualityoflife.OvariancancerpatientsinarecentstudyincludedcompletetoalmostcompletecontrolfromCINVamongthemostfavorablehealthstates,justbelowperfecthealthandclinicalremission.AdaptedfromSupportCareCancer2005;13:219-27.第17頁/共90頁CINV—DecreasedQualityofLifeAdaptedfromSupportCareCancer2005;13:219-27.第18頁/共90頁AdaptedfromBloechl-DaumBetal.JClinOncol.2006;24:4472.CINV—DecreasedQualityofLifeFLIEQuestionnaireHEC-FLIE>MEC-FLIEP=0.0049FLIE-nausea>FLIE-VomitingP=0.0097Thereisagreaternegativeimpacton

QOLfromnauseathanthereisfromvomitingThereisagreaternegativeimpacton

QOLfromHECthanthereisfromMECFLIE=FunctionalLivingIndex-Emesis;HEC=highlyemetogenicchemotherapy;MEC=moderatelyemetogenicchemotherapy.第19頁/共90頁SummaryoftheImportanceof

PreventionandTreatmentofCINVTherestillisahighlevelofanguishforCINVexperiencedbyourpatients.Ashealthcareprofessionals,wemaynotbeaccuratelypredictingthelevelofCINVexperiencedbyourpatients.CINVhasaenormousimpactonourpatientsqualityoflife.第20頁/共90頁MechanismsofCINVCentralmechanism:Chemotherapeuticagentactivatesthechemoreceptortriggerzone(CTZ).ActivatedCTZinvokesreleaseofvariousneurotransmitters,whichstimulatevomitingcenter.Peripheralmechanism:Chemotherapeuticagentcausesirritationanddamagetogastrointestinal(GI)mucosa,resultinginthereleaseofneurotransmitters.Activatedreceptorssendsignalstovomitingcenterviavagalafferents.Adaptedfrom:BergerAMetal.In:Cancer:PrinciplesandPracticeofOncology.

6thed.LippincottWilliams&Wilkins;2001:2869–2880.第21頁/共90頁AdaptedfromNEnglJMed2008;358:2482-94.第22頁/共90頁Serotoninand5-HT3ReceptorPathwayFirstrecognizedwithhigh-dosemetoclopramide.Developmentof5-HT3antagonistshashaddramaticimpact:Highlyeffectiveinacutevomiting,lesseffectivefordelayedevents.Optimaluseiswithdexamethasone.Primarymechanismofactionappearstobeperipheral.Adaptedfrom:BergerAMetal.In:Cancer:PrinciplesandPracticeofOncology.6thed.LippincottWilliams&Wilkins;2001:2869-80.GrallaRJetalJClinOncol1999;17:2971-94.AntiemeticSubcommitteeoftheMultinationalAssociationofSupportiveCareinCancer.AnnOncol1998;9:811-19.EndoTetalToxicology2000;153:189-201.HeskethPJetalEurJCancer2003;39:1074-80.第23頁/共90頁SubstancePandNeurokinin-1(NK1)

ReceptorPathwayHighdensityofsubstanceP/NK1receptorslocatedinbrainregionsimplicatedintheemeticreflex.PrimarymechanismofNK1receptorblockadeactionappearstobecentral.Effectiveforbothacuteanddelayedevents.Augmentsantiemeticactivityofa5-HT3receptorantagonistandcorticosteroid.Adaptedfrom:HargreavesRJClinPsychiatry2002;63(suppl11):18-24.SariaAEurJPharmacol1999;375:51-60.HeskethPJSupportCareCancer2001;9:350-54.第24頁/共90頁ConceptualModelofAcute&DelayedCINVAdaptedfromAndrews&Davis.In:AndrewsPLR&SangerGJ(Eds).EmesisinAnti-CancerTherapy:MechanismsandTreatment.London:Arnold;1993:147.5-HT3-sensitivephaseProkinetic-sensitivephaseSteroid-sensitivephaseDisruptedgutmotilityCellbreakdownproductsIntensityofemesisTime(days)0123455HTNK1-sensitivephase第25頁/共90頁PharmacogenomicsQuestforindividualizedtherapy.Identificationandcharacterizationofalargenumberofgeneticpolymorphisms(biomarkers)indrugmetabolizingenzymesanddrugtransportersmayprovidesubstantialknowledgeaboutthemechanismsofinter-individualdifferencesindrugresponse.第26頁/共90頁PharmacogenomicsPharmacogenomics-thestudyoftherelationshipbetweenspecificDNAsequencevariationsandtheactualeffectofadrug.CYP2D6isinvolvedinthemetabolismofallofthemostcommonlyavailableserotoninantagonists,exceptgranisetron,andtheirefficacyandsideeffectsmaythereforebeaffectedbytheCYP2D6

polymorphism.Asthisenzymeispolymorphic,severaldifferentallelesmaybepresentindifferentindividuals.第27頁/共90頁NumberofSubjectsIncreasingMetabolicCapacityEMPMURMPharmacogenomicsPolymorphicDistributionCYP2D6mutationsordeletions,poormetabolizer(PM),occurin10%ofthegeneralpopulation(UM)Ultrarapidmetabolizerphenotypeisobservedin2%ofthegeneralpopulation.EM(extensivemetabolizer),whichisthenormalorusualphenotype.第28頁/共90頁PharmacogenomicsinCINVKaiserstudiedtheimpactofpatientgenotypefor2D6(CYP2D6)onefficacyofondansetronandtropisetronforCINV.Theultrarapidmetabolizerpatientsexperiencedsignificantlymorenauseaandvomitingafterchemotherapy.Theimpactofgenotypeonvomitingincidencewasobservedduringbothearly(hours0to4)andlate(hours5to24)observationperiods,althoughdelayednauseaandvomitingwasnotevaluatedinthisstudy.Adaptedfrom:KaiserR,SezerO,PapiesA,etal:Patient-tailoredantiemetictreatmentwith5-hydroxytryptaminetype3receptorantagonistsaccordingtocytochromeP-4502D6genotypes.JClinOncol20:2805-11,2002.第29頁/共90頁Figure2.Meannumberofepisodesofvomiting({+/-}standarddeviation)experienced5-24hoursafterchemotherapyasafunctionofthenumberofactivecytochromeP450CYP2D6enzymegenesinpatientsreceivingtropisetron,5mgonceaday(A),andondansetron,8mgtwiceaday(B)PharmacogenomicsinCINVAdaptedfrom:KaiserR,SezerO,PapiesA,etal:Patient-tailoredantiemetictreatmentwith5-hydroxytryptaminetype3receptorantagonistsaccordingtocytochromeP-4502D6genotypes.JClinOncol20:2805-11,2002.第30頁/共90頁ANTIEMETICGUIDELINECONSENSUS-OfficialProcessSubscribedtoby9InternationalOncologyGroups-International:MASCCNorthAmerica:-U.S.ASCO,NCCN-CanadaCCOEurope:ESMO,EONSAfrica:SASMOAustralia:COSAAdaptedfromMASCCAntiemeticMarch2008GuidelineUpdate.第31頁/共90頁MASCC(PERUGIA)2004ANTIEMETICGUIDELINESANTIEMETICTREATMENTGUIDELINES

-TheFourEmeticRiskGroups-HIGHRiskinnearly

allpatients(>90%)MODERATERiskin30%to90%ofpatientsLOWRiskin10%to30%ofpatientsMINIMALFewerthan10%atriskAdaptedfromMASCCAntiemeticMarch2008GuidelineUpdate.第32頁/共90頁MASCC(PERUGIA)2004ANTIEMETICGUIDELINES-EmeticRiskGroups-SingleIVAgents-HIGHCisplatinMechlorethamineStreptozocinCyclophosphamide>1500mg/m2CarmustineDacarbazineMODERATEOxaliplatinCytarabine>1gm/m2CarboplatinIfosfamideCyclophosphamide<1500mg/m2DoxorubicinDaunorubicinEpirubicinIdarubicinIrinotecanAdaptedfromMASCCAntiemeticMarch2008GuidelineUpdate.第33頁/共90頁MASCC(PERUGIA)2004ANTIEMETICGUIDELINES-CommitteeI(3/5):EmeticRiskGroups-SingleIVAgentsLOWPaclitaxelDocetaxelMitoxantroneTopotecanEtoposidePemetrexedMethotrexate

DoxorubicinHCLliposomeinjectionMitomycinGemcitabineCytarabine<100mg/m25-FluorouracilBortezomibCetuximabTrastuzumabAdaptedfromMASCCAntiemeticMarch2008GuidelineUpdate.第34頁/共90頁MASCC(PERUGIA)2004ANTIEMETICGUIDELINESANTIEMETICTREATMENTGUIDELINES

-CommitteeI(5/5):EmeticRiskGroups-SingleOralAgents-HIGHHexamethylmelamineProcarbazineMODERATECyclophosphamideEtoposideTemozolomideVinorelbineImatinibLOWCapecitabine

TegafururacilMINIMALChlorambucilHydroxyureaL-Phenylalaninemustard6-ThioguanineMethotrexateGefitinibAdaptedfromMASCCAntiemeticMarch2008GuidelineUpdate.第35頁/共90頁PrinciplesofCareforAcuteHighlyand

ModeratelyEmeticSettingsUNANIMOUSCONSENSUS:CATEGORY1EVIDENCEUsethelowesttestedfullyeffectivedose.Noscheduleisbetterthanasingledosegivenbeforechemotherapy.Theantiemeticefficacyandadverseeffectsofserotoninantagonist

agentsarecomparableincontrolledtrials.Intravenousandoralformulationsareequallyeffectiveandsafe.Alwaysgivedexamethasonewitha5-HT3antagonistbeforechemotherapy.AdaptedfromMASCCAntiemeticMarch2008GuidelineUpdate.第36頁/共90頁Topreventacutevomitingandnauseafollowingchemotherapyofhighemeticrisk,athree-drugregimenisrecommendedincludingsingledosesof:5-HT3antagonistDexamethasoneAprepitant(orfosaprepitant)givenbeforechemotherapyisrecommended.MASCCLevelofconfidence:High MASCCLevelofconsensus:HighASCOLevelofevidence:IASCOGradeofrecommendation:AAdaptedfromslidefromMASCCAntiemeticMarch2008GuidelineUpdate.GuidelineforthePreventionofAcuteNauseaandVomitingFollowingChemotherapyofHighEmeticRisk:第37頁/共90頁Example-Womenreceivingacombinationofanthracycline+cyclophosphamiderepresentasituationwithaparticularlygreatriskofvomitingandnausea.Topreventacutevomitingandnauseainthesewomen,athree-drugregimenincludingsingledosesof:5-HT3antagonistDexamethasoneAprepitant(orfosaprepitant)givenbeforechemotherapyisrecommended.MASCCLevelofconfidence:ModerateMASCCLevelofconsensus:HighASCOLevelofevidence:IIASCOGradeofrecommendation:AAdaptedfromMASCCAntiemeticMarch2008GuidelineUpdate.GuidelineforthePreventionofAcuteNauseaandVomitingFollowingChemotherapyofModerateEmeticRisk(MEC):第38頁/共90頁InpatientswhoreceiveMEC,notincludingacombinationofanthracyclinepluscyclophosphamide:5-HT3receptorantagonist+Dexamethasoneisrecommendedforprophylaxisofacutenauseaandvomitinginthefirstcourse.

MASCClevelofconfidence:HighMASCClevelofconsensus:HighASCOlevelofevidence:IASCOgradeofrecommendation:AAdaptedfromMASCCAntiemeticMarch2008GuidelineUpdate.GuidelineforthePreventionofAcuteNauseaandVomitingFollowingChemotherapyofModerateEmeticRisk(MEC):第39頁/共90頁B.C.CancerAgencyAntiemeticregimensAdaptedfrom:GuidelinesforPreventionandTreatmentofChemotherapy-InducedNauseaandVomitinginAdults.

RetrievedJuly21,2008fromhttp://www.bccancer.bc.ca/NR/rdonlyres/8E898B5D-3F12-4623-8E32-5B3C429C58F7/28155/SCNAUSEA_1Mar08.pdf第40頁/共90頁ONSPuttingEvidenceintoPracticeAdaptedfromONSPEPNauseaRetrievedJuly21,2008from/outcomes/volume1/nausea/pdf/nauseaPEPCard.pdf第41頁/共90頁AdaptedfromONSPEPNauseaRetrievedJuly21,2008from/outcomes/volume1/nausea/pdf/nauseaPEPCard.pdfONSPuttingEvidenceintoPractice–Cont’d第42頁/共90頁CancerCareOntario-TelephoneNursingPractice-andSymptomManagementGuidelinesAdaptedfromCCOTelephoneAssessments.RetrievedJuly21,2008fromhttp://www.cancercare.on.ca/documents/NursingTelephonePracticeGuidelines.pdf第43頁/共90頁CancerCareOntario-TelephoneNursingPractice

andSymptomManagementGuidelinesAdaptedfromCCOTelephoneAssessments.RetrievedJuly21,2008fromhttp://www.cancercare.on.ca/documents/NursingTelephonePracticeGuidelines.pdf第44頁/共90頁CommonCINVChallengesChallengesinmultiple-daychemotherapyregimensBreakthroughCINVAnticipatoryCINVDelayedCINV第45頁/共90頁Multiple-DayChemotherapyRegimensChallenge–Patientsreceivingmulti-daychemotherapy(chemotherapyadministeredoverseveraldayspercycle)areatriskforbothacuteanddelayednauseaandvomiting.Itisdifficulttorecommendappropriateantiemeticsforeachdaysinceacuteanddelayedmayoverlapaftertheinitialdayofchemotherapy.Theperiodofriskfordelayednauseaandvomitingalsodependsontheemetogenicpotentialofthelastchemotherapyagentadministeredintheregimen.AdaptedfromNCCNPracticeGuidelinesinOncology–Version3.2008.Antiemesis,第46頁/共90頁Multi-DayChemotherapyRegimens(continued)A5-HT3receptorantagonistshouldbeadministeredpriortoeachdays1stdoseofmoderatelyorhighly-emetogenicchemotherapy.DexamethasoneshouldbeadministeredoncedailyeitherorallyorIVforeverydayofchemotherapyandfor2-3dayspostchemotherapy.Aprepitantmaybeusedformulti-daychemotherapy.Aprepitant125mgonday1,thenaprepitant80mgdailyondays2and3alongwithdexamethasone.BasedonPhaseIIdata,aprepitantmaybesafelyadministeredondays4and5afterchemotherapy.AdaptedfromNCCNPracticeGuidelinesinOncology–Version3.2008.Antiemesis,第47頁/共90頁BreakthroughCINVBreakthroughemesisreferstovomitingthatoccursdespiteprophylactictreatmentand/orrequiresrescue.Refractoryemesisreferstoemesisthatoccursduringsubsequenttreatmentcycleswhenantiemeticprophylaxisand/orrescuehavefailedinearliercycles.Challenge-Breakthroughnauseaandvomitingrepresentsadifficultsituationasongoingrefractorynauseaishardtoreverse.AdaptedfromNCCNPracticeGuidelinesinOncology–Version3.2008.Antiemesis,第48頁/共90頁BreakthroughCINV(continued)ManagementStrategies-Givearoundtheclockadministrationversusprn.

Additionalagentsshouldbefromadifferentdrugclassthaninitialtherapy.Noonetreatmentisbetterthantheother.Possibilitiesinclude:dopamineantagonists,metoclopramide,haloperidol,cannabinoids,corticosteroids,oragentssuchaslorazepamIfpatienthasdyspepsia,considerantacidtherapy(H2blockerorProtonPumpInhibitor).AdaptedfromNCCNPracticeGuidelinesinOncology–Version3.2008.Antiemesis,第49頁/共90頁BreakthroughCINV–Cont’dAdaptedfrom:GuidelinesforPreventionandTreatmentofChemotherapy-InducedNauseaandVomitinginAdults.RetrievedJuly21,2008fromhttp://www.bccancer.bc.ca/NR/rdonlyres/8E898B5D-3F12-4623-8E32-5B3C429C58F7/28155/SCNAUSEA_1Mar08.pdf第50頁/共90頁Adaptedfrom:1.RoscoeJA,etal.JPainSymptomManage2000;20:113.2.MorrowGR,etal.SupportCareCancer1998;6:244.AnticipatoryCINVAnticipatorynauseaand/orvomitingistheoccurrenceofnauseaand/orvomitingbeforepatientsreceivetheirchemotherapytreatment.Becauseitisaconditionedresponse,itcanonlyoccurafteranegativepastexperiencewithchemotherapy.Challenge-Anticipatorynauseaand/orvomitingoccursin18%to57%ofchemotherapypatients.Youngerpatientsmaybemoresusceptibleastheygenerallyreceivemoreaggressivetherapyandhavepooreremesiscontrolthanolderpatients.第51頁/共90頁AnticipatoryCINV(continued)ThemosteffectivewaytotreatistopreventCINVbyusingoptimalantiemeticsduringeverycycleoftherapy.Either:AlprazolamPO0.25to0.5mgt.i.d.beginningonthenightbeforetreatmentOR;Lorazepam0.5-2mgPOonthenightbeforeandthemorningoftreatment.BehavioraltherapySystemicdensensitizationAdaptedfromNCCNPracticeGuidelinesinOncology–Version3.2008.Antiemesis,第52頁/共90頁AdaptedfromGrunbergetal.Cancer2004;100:2261.DelayedCINVChallenge-Delayedemesisis2.5timesmoreprevalentthanacuteemesis.Formoderatelyemetogenicchemotherapy:Delayednauseaexceedsacutenauseaby16%.Delayedemesisexceedsacuteemesisby15%.Forhighlyemetogenicchemotherapy:Delayednauseaexceedsacutenauseaby27%.Delayedemesisexceedsacuteemesisby38%.第53頁/共90頁PrognosticFactorsforDelayedCINVStrongestpredictorofdelayednauseaandvomitingwastheoccurrenceofacutenauseaandvomiting.Patientsaged52yearsoryoungerandwomenweremorelikelytohavedelayednauseathanwerethoseolderthan52yearsandmen.Ahighexpectationofnauseawasasignificantpredictorofmoreseverenausea.AdaptedfromTheLancetOncologyOctober2005;Vol(6):Issue(10):765-72.第54頁/共90頁Case1InitialPresentationMaryT.isa56-year-oldfemalewhowascompletelyasymptomaticwhenaroutinemammogramshowedtwolesions.Sheunderwentdiagnostictestingandhadamastectomyandauxiliarylymphnodedissection.Diagnosis–T3(morethan5cm)N0(0/6lymphnodes)M0.poorlydifferentiatedinvasiveductalcarcinomaofrightbreast,ER/PRpositiveandHER-2/neunegative.第55頁/共90頁InitialPresentationPASTMEDICALHISTORY:Unremarkable.SOCIALHISTORY:Schoolteacher,married,motheroftwogrownchildrenlivingaway,nonsmoker,occasionaldrinkontheweekends.MEDICATIONS:Ranitidine150mgb.i.d., Lorazepam1mgprnSYSTEMINQUIRY:Unremarkable.Allergies:NKA(drugs,food,environmentalallergens)第56頁/共90頁FirstCycleofChemotherapy(FEC)ThepatientisprescribedFEC(Fluorouracil,Epirubicin,Cyclophosphamide)–for3cyclesfollowedbyTaxoterefor3cycles.ShewasgivenOndansetron8mgandDexamethasone8mgpriortoherfirstcycleofchemotherapy.ShewasgivenaprescriptionforOndansetron8mgandDexamethasone4mgpob.i.d.x2dayspostchemotherapyaswellasMetoclopramide10mgpoq6hprntobetakenpostchemotherapy.第57頁/共90頁NauseapostCycle1Whenshereturnedforcycletwosheinformedthepharmacistthatshehadvomitedonday2andthatshehadexperiencednauseafordays2-5postchemotherapy.Sheratesthisnauseaasa8/10fordays2-4and6/10forday5.第58頁/共90頁Case1:Question1Whatanti-emeticswouldyourecommendtobegivenpriortochemotherapyforhersecondcycleofFEC?Metoclopramide10mgOndansetron8mg,Dexamethasone8mgand Aprepitant125mgOndansetron8mgandDexamethasone8mg第59頁/共90頁Womenreceivingacombinationofanthracycline+cyclophosphamiderepresentasituationwithaparticularlygreatriskofvomitingandnausea.Topreventacutevomitingandnauseainthesewomen,athree-drugregimenincludingsingledosesof:5-HT3antagonistDexamethasoneAprepitant(orfosaprepitant)givenbeforechemotherapyisrecommended.AdaptedfromMASCCAntiemeticMarch2008GuidelineUpdate.AnswerQuestion1=BGuidelineforthePreventionofAcuteNauseaandVomitingFollowingChemotherapyofModerateEmeticRisk(MEC):第60頁/共90頁Case1:Question2Whatanti-emeticswouldbeofferedtothispatientasananti-nauseatakehomeprescriptionfortheFEC(cycle2)regimen?A.Dexamethasone8mgbidx3daysandMetoclopramide10mgq6hprn.B.Metoclopramide10mgq6hprn.C.Aprepitant80mgondays2and3,Ondansetron8mgandDexamethasone4mgbidx2daysandMetoclopramide10mgq6hprn.第61頁/共90頁AnswerQuestion2Adaptedfromhttp://www.bccancer.bc.ca.第62頁/共90頁Case1:Question3WhatotheractionscanthepharmacisttaketohelpM.T.controlherCINV?第63頁/共90頁AnswerQuestion3Explorepatientadherencewithanti-emetics.Assesseffectiveness/ineffectivenessofanti-emeticplan.Followuptoxicityassessments(useCCOtelephonetoxicityguidelines).CINVeducation.Communicationwithherotherhealthcareproviders.Patientnauseadiary(CANOpatienteducationforCINV).Promotepatientinvolvementthroughpatientresources:ChemotherapyandYou:AGuidetoSelf-HelpDuringCancerTreatment,/cancerinfo/chemotherapy-and-you第64頁/共90頁Case1:Question4Thepharmacistasksthepatientwhatmedicationssheiscurrentlytaking.SheinformsthenursesheistakingWarfarin,MetoprololandASA.

ShouldshebeconcernedaboutadruginteractionwithWarfarinandAprepitant?第65頁/共90頁Case1:Question5WhichofthefollowingmayoccurwiththeadditionofaprepitanttoM.T’sregimen?A.INRmaydeclineB.INRmayincreaseC.Warfarinlevelsmayrise第66頁/共90頁AnswerQuestion4and5

WarfarinAprepitantInteractionAprepitantisaCYP3A4substrate,a3A4inhibitorandinducer,anda2C9inducer.INRmaydecline.

AdaptedfromAprepitantMonograph.RetrievedJuly22,2008fromhttp://www.cancercare.on.ca/pdfdrugs/aprepitant.pdf第67頁/共90頁ImportanceofMedicationReconciliationPilotProjectofMedicationReconciliationinSt.John’s,NewfoundlandCancerCenterSummerprojectPharmacyStudentsObtaininganaccuratemedicationhistoryforchemotherapypatients第68頁/共90頁TotalNumberofMedicationsvs.TotalNumberofInaccuraciesorOmissionsCancerCareProgram第69頁/共90頁IdentificationofthenumberofpatientswithinaccuraciesoromissionsaswellasthenumberofdrugrelatedproblemsidentifiedCancerCareProgram第70頁/共90頁IdentificationofthenumberofpatientswithinaccuraciesoromissionsaswellasthenumberofpatientstakingOTC/HerbalsCancerCareProgram第71頁/共90頁StartingDocetaxelafterFECM.T.completedherthreecyclesofFECaspartoftheFEC-Dregimen.SincetheadditionofAprepitant,hernauseacontrolhasbeenmuchbetter.SincesheisstartingDocetaxel,sheneedstotakeDexamethasone8mgpob.i.d.for3days,starting24hourspriortochemotherapy.ThemedicaloncologyteamwouldliketokeepM.T.onAprepitantduetoherimprovedresponse.第72頁/共90頁Case1:Question6Astheoncologypharmacist,youtelltheteamthattheyneedtobeconcernedaboutAprepitantdruginteractions.WhichofthefollowingwouldbecorrecttotelltheteamaboutAprepitant:A. AprepitantisaSubstrateforCYP3A4,andModerateInhibitorofCYP3A4.B. AprepitantisaWeakInducerofCYP3A4andCYP2C9.C. BothAandBarecorrect.第73頁/共90頁AnswerQuestion6-AprepitantandP450SubstrateforCYP3A4,CYP2C19andCYP1A2WeakInducerofCYP3A4andCYP2C9ModerateInhibitorofCYP3A4WeakinhibitorofCYP2C9