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LogKill:ClinicallyDetectableTumor:
1Gram=1BillionCells----------------
EffectivelyDosedChemoKillsby1stOrderKinetics
(ConstantFractionofCancerCellsEachTime)
ResidualCancerCellsKilledBy:ImmunologicProcesses
Apoptosis
GompertzianGrowth:AsTumorsIncreaseinSize,theirGrowthFraction(GF)
Decreases,causingHypoxicConditions.AsTumorsDecreaseinSize,theirGrowthFraction(GF)
Increases,makingthemMoreSusceptibletoChemotherapy.
SmallTumors=MoreResponsivetoChemoLargeTumors=LessResponsivetoChemo
RBandP16:RetinoblastomaP53:LiFraumeniSyndrome
Pyrimidines:Thymine(5-MethylUracil)
CytosinePurines:GuanineAdenine
Nucleoside:Nucleobase+PentoseSugarNucleotide:Nucleoside+PhosphateGroups
Drug DrugClass MechanismofAction Indications AdverseEffects ResistanceMechanisms
NitrogenMustardAlkylator
CellCycleNon-Specific(Radiomimetic)
ActThroughCovalentBondingofAlkylGroupstoIntra-CellularMarcomolecules.
AlkanesareMissingOneHydrogen,MakingThemVERYReactive.
TheyFormAdductswithNucleophillicMolecules---------------------------------------------------
AlkylationofDNABasesLeadstoLethalToxicityinCancerN7PositionofGuanine
Monofunctional:OneUnpairedElectron-SingleStrandBreaks
Bifunctional:TwoUnpairedElectrons--CrossLinking
Hodgkin'sDiseaseIV
Vesicant(NitrogenMustardistheWorst)--------------------------------------------
ToxicityWORSEinCellsDeficientinDNARepairEnzymesExample:AtaxiaTelangiectasiaSyndrome
--------------------------------------------SecondaryMalignancies(AML)
CausedbyDNADamageWithoutCellDeath---------------------------------------------
BoneMarrowSuppression:(WBCsandPlatelets)Occurs:7-10DaysPostRx
Recovers:7-10Days-------------------------------------------------------FormationofTrappingAgent(Glutathione)
IncreasedIntracellularThiol(Glutathione)Concentration.ThisNeutralizesAlkylation
(GeneAmplification)---------------------------------------------------
ChangeinDNARepairEnzymesAmountofEnzyme(GeneAmplification)
Efficiency(Mutation)
NitrosoureasCarmustine(BCNU)Lomustine(CCNU)
Semustine(Methyl-CCNU)
AlkylatorCellCycleNon-Specific
(Radiomimetic)
WorkSimilarlytoClassicAlkylator(Above)CovalentlyBindwithNucleicAcids
CauseCross-Linking
FATSOLUBLECrossBBB(BrainMetastasis)
MelanomaBrainTumors
PROLONGEDBoneMarrowSuppression SameasAbove
BusulfanAlkylator
CellCycleNon-Specific(Radiomimetic)
WorkSimilarlytoClassicAlkylator(Above)HistoricallyUsedforCMLReplacedbyGleevac
PulmonaryToxicity SameasAbove
TemozolomideAlkylator
CellCycleNon-Specific(Radiomimetic)
SameasAboveTetrazideDerivative(AromaticRing-4HAtoms)
OralPro-DrugCrossesBBB
ImprovesSurvivalinGliomaswhenCombinedwithRadiationTherapy
SameasAbove SameasAbove
CyclophosphamideAlkylator
CellCycleNon-Specific(Radiomimetic)
CommonDrugActiveIntermediates
(PhosphoramideMustardandACROLEIN)
Well-AbsorbedOrallyWidestClinicalUsage
BreastCancersLymphomasLeukemias
MyelosuppressionAcroleinToxicity
HemorrhagicCystitis(PreventbyForcingHydration,Diuresis,andParticular
AttentiontoUrinaryObstruction(BPH))
SameasAbove
IfosfamideAlkylator
CellCycleNon-Specific(Radiomimetic)
ToxicityofACROLEINAcrolein:
ProducedbyBurningFatAnExtremelyToxicIntermediary,Particularlytothe
BladderMucosa(OlderPatientswithBPH)CausesHemorrhagicCystitis
-----------------------------------------------------------------ModifiedwithMESNA:
2-MercaptoEthaneSulfonateSodium(NA)SuppliesFreeThiolGroup,whichBindstoandInactivates
Acrolein
TesticularCancerSarcoma
LungCancer
AcroleinToxicityHemorrhagicCystitis(MostCommoninBPHPatients) SameasAbove
Drug DrugClass MechanismofAction Indications AdverseEffects ResistanceMechanisms
Methotrexate(-trex=Anti-Folate)
Anti-MetaboliteCellCycleSpecific
Anti-Folate
CloseStructuralResemblancetoaMoleculeRequiredforNormalPhysiologicFunctioning,andExertingitsEffectbyInterferingwiththeUtilizationofthisEssentialMolecule.
InhibitionofDNA/RNA/ProteinSynthesis------------------------------------------------------------
VerySimilartoFolicAcidPreventsRegenerationofReducedFolateby
BlockingDihydrofolateReductaseNoTetrahydrofolate=NodUMP=NoDNASynthesisThymidiylateSynthetaseRequiresTetrahydrofolate
ChoriocarcinomaDoesNotCrossBBBIntrathecalChemo
(AttainHighCSFConcentrationswithMinimalSystemicToxicity)-------------------------------------------------
LeucovorinFolinicAcidRescue:WithUseofHighDoseMTXCancerCellshaveHighGF
MTXEffectisMoreRapidwithHigherGFCellPopulations(Cancer)
MayRescueLowerGFPopulation(Non-CancerousTissue)withExcess
ReducedFolate(GivenAfterMethotrexate)Dangerous--TimingisCritical
MinimalSystemicToxicityBecauseWhenyouInjectItDirectlyIntotheCSF,ItCannotCrossBackOut.
----------------------------------------------------------------------BoneMarrowSuppression(7-10Days)
SkinRashesMucositis(7-10Days)-->Infections
Hepatotoxicity(MoreCommonwithChronicUse)PulmonaryToxicity
----------------------------------------------------------------------3rdSpacing:
MethotrexateCollectsinPleuralEffusions&AsciticFluidSubsequentSlowReleaseofDrugMimickingaSlowInfusionwithIncreasedBoneMarrowandMucosal
Toxicity(Unpredictable)
IncreasedProductionofDHFR(GeneAmplification)
DecreasedAffinityofDHFRforMTX(Mutation)
-------------------------------------------------OftenMoreActiveifPolyglutamatedAdditionofGlutamicAcidResiduesIntracellularlytoMethotrexateDecreasesCellularEffluxof
PolyglutamatedDrugIncreasesDrugActivity/ExposureTimeCellsthatCannotPolyglutamateAreRelativelyResistanttoEffectofMTX.CancerCellMutationcanDecrease
PolyglutamationCanEitherbeInheritantlyPoor
PolyglutamatorsorUndergoMutations
5-Fluorouracil5-FU
Anti-MetaboliteCellCycleSpecificPyrimidineAnalog
Normal:dUMP-->dTMP-->DNASynthesis-------------------------------------------------------
dUMPCannotbeMethylatedtodTMPinthe5'PositionBecauseThereisaFluorineThere
5F-dUMPisCompetingwithdUMPfortheThymidylateSynthetaseEnzyme
DecreaseinDNASynthesis-------------------------------------------------------
SecondaryMechanism:5F-UMPisIncorporatedintoRNA
ActsasFalsePyrimidineInhibitsTranscription
-------------------------------------------------------------------------PRPP:
NeededtoSecondarilyActivate5-FUNeededtoSynthesizePurines
InhibtedbyAllopurinol
CornerstoneforRxColonCancerBreastCancerGIMalignancies
----------------------------------------------Flucytosine(5-Fluorocytosine):
Anti-FungalAgentAFluorinatedPyrimidineAnalogueAlsoBioactivatedto5-FdUMPInhibitingTSinFungalCells
GI(Mucositis)Myelosuppression
Skin-SunSensitivity(VenousDiscoloration) 1.IncreasedExpressionofTSEnzyme(GeneAmplification)
2.ReducedDrugSensitivityofTSEnzyme(Mutation)
3.DecreasedActivationof5-FUa.DecreasedActivatingEnzymes(Mutation/Underexpression)orb.DecreasedPRPPSecondaryto
Allopurinol------------------------------------
GivingAllopurinolInhibitsPRPP,whichSecondarilyActivates5-FU.ThismeansAllopurinolDECREASESActivityof5-FU
Capecitabine(Xeloda)
Anti-MetaboliteCellCycleSpecificPyrimidineAnalog
ProdrugConvertedto5-FUintheLiverandthentoActiveDrugin
LiverandTumorTissueIncreasesAreaUndertheCurve
(ProlongedExposureAffectsHigher%ofCyclingCells)
OrallyMimicks5-FUInfusion
LowDoseDeliveredOverLongTerm
HandFootSyndrome:VasospasminHands/Feet
CytosineArabinoside(ARA-C)
Anti-MetaboliteCellCycleSpecificPyrimidineAnalog
ArabinoseSugarisSubstitutedforDeoxyriboseSugarIncorporatedintoDNAInhibitsDNAPolymeraseInhibitsDNAElongation
AMLSevereBoneMarrowSuppression
GI(Mucositis)UnusualNeuroToxicity(CerebellarDysfunction)-Ataxia
IncreasedActivityofCytidineDeaminase(InactivatesDrug--GeneAmplification)DecreasedActivityofDeoxycytidine
Kinase(ActivatesDrug--Mutation)
DecreasedAffinityofDNAPolymerase(Mutation)
OverexpressionofDNAPolymerase(GeneAmplification)
GemcitabineAnti-MetaboliteCellCycleSpecificPyrimidineAnalog
CytosineAnalog(HReplacedbyF)StructurallySimilartoARA-C
butInhibitsDNAPolymeraseANDRibonucleotideReductase
PancreaticCancer
AzacitadineAnti-MetaboliteCellCycleSpecificPyrimidineAnalog
InhibitsMethytransferaseCausingHypomethylationofDNA,LeadingtoCellDeathManyTumorSuppressorGenesareSilencedbyDNA
MethylationduringCarcinogenesis(EpigeneticEffect)
IncreasesTumorSuppressorActivityDrugisIncorporatedintotheGenome,Actingas"Real"
Anti-Metabolite
MyelodysplasticSyndrome
6-Mercaptopurine(6-MP)
6-Thioguanine(6-TG)
Anti-MetaboliteCellCycleSpecificPurineAnalog
Hypoxanthine-->GuanineviaHypoxanthine-GuaninePhosphoribosylTransferase
Enzyme(HGPRT)ThisRecyclesHypoxanthine-->Purines.
6-MPand6-TGBLOCKHGPRT(WithSulfur)-->NoPurineRecycling-->NoDNASynthesis-------------------------------------------------------
PRPP:NeededtoSecondarilyActivate5-FU
NeededtoSynthesizePurinesInhibtedbyAllopurinol
(CausesFeedbackInhibitionofAmidophosphoribosylTransferase(Atase)NeededtoConvertPRPPto
PhosphoribosylamineRateLimitingEnzymeinPurineSynthesis
Leukemia--------------------------------------------
Lesch-NyhanSyndrome:HGPRTDeficiencyIncreasedPRPPLeadstoIncreasedPurineSynthesis
UtilizingPRPP.IncreasedUricAcid
GoutIntellectualDisability
Self-MutilatingBehaviorX-LinkedRecessive
MyelosuppressionMucositisDiarrhea
Nausea&Vomiting
DecreasedAffinityfortheActivatingEnzymeHGPRT(Mutation)
IncreasedDrugDegradation(GeneAmplification
viaXANTHINEOXIDASE)IfyouTreatGoutwithAllopurinol,andthePatientison6-MP/6-TG,theAllopurinolwillALSOBreakDowntheChemotherapy
(andthePRPP),IncreasingToxicity
Cladribine(2-Chlorodeoxyadenosine)
Anti-MetaboliteCellCycleSpecificPurineAnalog
AdenosineAnalog(2CDA)InhibitsAdenosineDeaminaseAdenosineOveraccumulates
CurativeinHairyCellLeukemia
HydroxyureaAnti-MetaboliteCellCycleSpecific
UreaAnalog
InhibitsRibonucleotideReductaseNeededtoConvertRibonucleotidesto
DeoxyribonucleotidesInhibitsDNASynthesis
SickleCell-IncreasesHbFCML
MyelosuppressionNausea&Vomiting
Diarrhea
MutationorOver-ExpressionofRibonucleotideReductase
Drug DrugClass MechanismofAction Indications AdverseEffects ResistanceMechanisms
Doxorubicin(Adriamycin)
DaunorubicinIdarubicinEpirubicin
Anthracyclines(StreptomycesDerivative)
CellCycleSpecific
IntercalatesBetweenBasePairs(BlocksDNA/RNASynthesis)
----------------------------------------------------------------InhibitsTopoisomerase-2
(CausesDNAStrandBreakage)----------------------------------------------------------------
GeneratesOxygen/HydroxylFreeRadicals(CausesDNAStrandBreakage/CellMembraneDamage)
TheRedDevil:NHL
BreastCancerSarcoma
CardiacToxicity(FreeRadical-->CardiacMuscle)
SynergisticwithOtherDrugs(LikeTrastuzumab)Antidote:
Dexrazoxane(Zinecard):IronChelatingAgent,PreventingtheFormationof
Anthracycline-GeneratedFreeRadicals--------------------------------------------------------------------
BoneMarrowSuppressionAlopecia
SevereNauseaandVomitingSecondaryMalignancies
Multi-DrugResistance:MediatedbyP-Glycoprotein
(AnATP-DependentDrugEffluxPump)
DactinomycinAnthracyclines
(StreptomycesDerivative)CellCycleSpecific
IntercalatesBetweenBasePairs----------------------------------------------------------------
BindsatTranscriptionInitiationComplex(InhibitsRNAElongationbyRNAPolymerase)
-------------------------------------------GoldColor
Wilm'sTumor MyelosuppressionSevereVesicant
BleomycinAnthracyclines
(StreptomycesDerivative)CellCycleSpecific
IntercalatesBetweenBasePairs(BlocksDNA/RNASynthesis)
----------------------------------------------------------------ProducesSingle&DoubleStrandBreaks
----------------------------------------------------------------GeneratesOxygen/HydroxylFreeRadicals
(CausesDNAStrandBreakage/CellMembraneDamage)-----------------------------------------------------------------
OnlyDrugwithPre-DominatelyG2ActivityDisruptsSynthesisofComponentsNeededforMitosis
TesticularCancerHodgkin'sDisease
NHL
LungToxicity(FreeRadical-->Lung)AnaphylacticReaction
SkinToxicity
Multi-DrugResistance:MediatedbyP-Glycoprotein
(AnATP-DependentDrugEffluxPump)
Drug DrugClass MechanismofAction Indications AdverseEffects ResistanceMechanisms
VINcaAlkaloidsVINblastineVINcristineVINdesineVINorelbine
MadagascarPeriwinkleCellCycleSpecific
BindtoMicrotubuleProtein(Tubulin)CauseDepolymerizationofMicrotubules
PreventsSpindleFormation(LeadstoMitoticArrest)
Hodgkin'sDiseaseNHL
LungCancerGliomas
BreastCancer
TubulinisSimilartoMyelin--PeripheralNeuropathyDose-Dependent
SensoryNeuropathy:ReversibleMotorNeuropathy:IrreversibleAutonomic:Unpredictable
VincristineisNOTasMyelosuppressiveasOtherAgents
Multi-DrugResistance:MediatedbyP-Glycoprotein
(AnATP-DependentDrugEffluxPump)
TaxanesPaclitaxelDocetaxelAbraxaneCabazitaxel
YewTreeCellCycleSpecific
BindtoTubulinEnhancesTubulinPolymerization
PreventsSpindleDisassociationCausingMitoticArrest
OvarianCancerBreastCancerLungCancer
BoneMarrowSuppressionAllergies(Pre-TreatwithCorticosteroids)
Myalgias/ArthralgiasNeurologic
Skin(ParticularlyNails)-Beau'sLines**UseofSteroidstoPreventAcuteToxicityisCritical**
Multi-DrugResistance:MediatedbyP-Glycoprotein
(AnATP-DependentDrugEffluxPump)CabazitaxelisNOTInhibitedbyMDR
Pulmonary Fibrosis
PodophyllotoxinsEtoposideTeniposide
ExtractofMandrakePlant(NightshadeFamily)CellCycleSpecific
InhibitDNATopoisomerase-2(AndTubulinPolymerization)
TopoisomerasesAllowBreakageofBothDNAStrands,UnwindingofDNA,andRe-AnnealingoftheStrands.
InhibitDNAandRNASynthesis
TesticularCancerLungCancer(SmallCell)
NHLUnpredictableHypotension
Multi-DrugResistance:MediatedbyP-Glycoprotein
(AnATP-DependentDrugEffluxPump)
CamptothecinsIrinotecanTopotecan
HappyTreeDerived(CamptothecaAcuminata)
CellCycleSpecific
InhibitDNATopoisomerase-1LeadstoArrestofDNAReplicationandCellDeath
Irinotecan:MetastaticColonCancer
Topotecan:SmallCellLungCancer
Irinotecan:ExcessiveDiarrheaRequiringAnti-MotilityAgents
AlsohasUniqueAcuteCholinergicSideEffectRequiringATROPINE
(SuddenSalivation,Tearing,UrgetoDefecate,Bradycardia)
DoesNOTAppeartobeMDRMediatedMutation/Overexpressionof
Topoisomerase-1
Drug DrugClass MechanismofAction Indications AdverseEffects ResistanceMechanisms
CisplatinumCarboplatinumOxaliplatinum
PlatinumComplexesCellCycleNon-Specific
HeavyMetalsCanMoldShape--ActasAlkylatorsExtremelyDifficulttoEliminate
CurativeinMostGermCellTumors
Nephrotoxicity:IncreaseParenteral/OralHydration
UseVolumeExpanders(Mannitol)toForceDiuresisReplacePotassiumandMagnesium
Amifostine:ThiolCytoprotectiveAgentScavengesReactiveCisplastin
MetabolitesinNormalTissueCausesNecrosisorApoptosisofCellsofProximalTubule
LeadingtoWastingofMagnesiumandPotassium----------------------------------------------------------------
Neurotoxicity:8thNerveSomeProtectiveEffectofCalcium/Potassium
Cold-InducedNeuropathy:LaryngopharyngealDysesthesia:
AssociatedwithOxaliplatinCanBePreventedbyAvoidanceofColdAirandDrink
MonitorHearingLoss
Multi-DrugResistance:MediatedbyP-Glycoprotein
(AnATP-DependentDrugEffluxPump)----------------------------------------------------
IncreasedProductionofIntracellularThiolIncreasedProductionofDNARepair
EnzymesFormationofTrappingAgent
(Glutathione)
Drug DrugClass MechanismofAction Indications AdverseEffects ResistanceMechanisms
L-Asparaginase NaturallyOccuringEnzymeGuineaPigSerum
MalignantLymphocytes:RelativelyLOWLevelsofAsparagineSynthetaseL-AspaginaseHydrolysesCirculatingAsparagine.
Thisleadstolessavailabilityofasparaginefortumorcellstherebyinhibitingtumorproteinsynthesisandcell
proliferation.Non-MalignantCellsCellsareRelativelyProtected
ALL Pancreatitis
Drug DrugClass MechanismofAction Indications AdverseEffects ResistanceMechanismsArsenicTrioxide
TransRetinoicAcid ArsenicDerivativeDerivedfromArsenic"Metalloid"
UncertainMechanismofAction(InducesApoptosis?)InCombinationwithRetinoicAcidfor
AcutePromyelocyticLeukemiaInterruptsATPProductionLeadingtoMulti-SystemFailure
Bortezomid ProteosomeInhibitorProteosome:
CytoplasmicProteaseComplexRequiredtoDegradeUnneededProteins
MultipleMyelomaMantleCellLymphoma
Thalidomide GlutamicAcidDerivativeGlutamicAcidDerivative
InhibitsAngiogenesisbyInterruptingVEGFProcessesMultipleMyeloma BIRTHDEFECTS
Lenalidomide GlutamicAcidDerivative
Anti-AngiogenesisDrugDecreasesBoneMarrowStromalCellSupport
Anti-OsteoclasticImmunomodulatoryActivity(IMiD's)
MultipleMyeloma BIRTHDEFECTS
Drug DrugClass MechanismofAction Indications AdverseEffects ResistanceMechanismsTamoxifen
FlutamideBicalutamideEnzalutamide
SERM
AWeakEstrogenBlockstheEstrogenReceptor(ER)inBreastCancerCells
Bicalutamide/Enzalutamide:BlockstheAndrogenReceptor
Pre/PostBreastCancer
ThromboembolicDisease-EstrogenEffectEndometrialCancer-EstrogenEffect(DoesNOThappenwithRoloxifen)HotFlashes-Anti-EstrogenEffect
Retinopathy
ChangeinERExpressionMutationofER
SelectionofERNegativeCells
AminoglutethimideVeryToxic
RequiresConcurrentSteroidNoLongerUsed
AnastrozoleLetrozole
ExemestaneAromataseInhibitors Testosterone-->EstrogenInhibitor Post-MenopausalBreastCancer
ToxicityduetoEstrogenWithdrawal:(SUPER-Menopause)OsteoporosisHotFlashesAnthralgias
ProgestinsMegestrolAcetate
MedroxyprogesteroneProgesterone
DecreasesActivityofEstrogenReceptor(Down-Regulation)
IncreaseWeightinCancerPatients Hyperventilitation
LeuprolideGoserilin LHRHAnalogs
EmptiesthePituitaryofLH,FSH(FlareEffect)SubsequentlyDecreasesPituitaryReleaseofLH,FSHResultsinDecreasedEstrogenSynthesisbyOvary
BreastCancerProstateCancer
InducingMenopause
Toxicity:FlareEffectLastsApproximately10Days
CanbeInhibitedbyAndrogenReceptorBlockers
Abiraterone AndrogenProductionInhibitorSuppressesTesticularAndrogenProduction
DoesNOTAffectAdrenal/ProstaticAndrogenProductionInhibitsCYP17EnzymeComplexinTestes
AlsoBlockCortisolCausesIncreaseinACTH(Feedback)=HypertensionGivewithPrednisone(Cortisol)ToPreventThis
Drug DrugClass MechanismofAction Indications AdverseEffects Contraindications
Corticosteroids
UnknownMalignantLymphocyteshaveSteroidReceptorthatLyses
theCellswhenActivated(SteroidsCauseApoptosisofCancerCells)
Hodgkin's/NHLSupportiveCare:Anti-Nauseant
AppetiteStimulantDecreasesCerebralEdema
Co-Analgesic
FluidRetentionGlucoseIntoleranceProximalMyopathy
InsomniaImmunosuppressionIncreasedAppetite
SkinChangesStressUlcers
Rituximab CD20MOABMediatesAntibodyDependentCellularToxicityandComplementDependentCytotoxicitybyMaking
LymphocytesMoreVisibleB-CellLymphoma
InfusionRelated:TumorLysisSyndrome
ProgressiveMulti-FocalLeukoencephalopathyAllergies
AutoimmunePatients
Ipilimumab CTLA-4MOAB
CytotoxicT-LymphocyteAntigen4(CTLA-4)isanInhibitoryRegulatorofT-CellImmuneResponses.ItInhibitsImmuneDefenseAgainstTumorCells.
BlocksCTLA-4,DisinhibitingT-CellActivity
UsedinImmuneSensitiveCancer(Melanoma)
10-20%Immune-MediatedGIToxicity(TreatwithSteroids,Infliximab)
NivolumabPD-1PD-L1
ImmuneCheck-PointInhibitors
ProgrammedDeath-1PD-1:OnT-Cell
PD-L1:OnTumorCellsThisDown-RegulatestheImmuneSystem.
TheDrugActivatestheImmuneSystemtoAttackTumors(ByInhibitingPD)
AutoimmuneSideEffects
TrastuzumabPertuzumab
Her-2/NeuBlockerEGFRBlocker
MOABHer-2/NeuBlockerEGFRBlocker BreastCancer CardiacToxicity
NotUsedwithAnthracycline(BothCauseCardiacToxicity)
Cetuximab Non-HER-2EGFRBlockerMOAB
Non-HER-2EGFRBlockerMarthaStewartDrug
SquamousCellHeadandNeckCancerWild-TypeKRASColonCancer
AcneiformEruption
Panitumumab Non-HER-2EGFRBlockerMOAB
Non-HER-2EGFRBlocker Wild-TypeKRASColonCancer
Bevacizumab VEGFMOABInhibitNewVesselFormation(BlockingEndothelialCells)
ColonCancerAndrefractoryGliomas
DelayedWoundHealingProteinuriaHypertension
DenosumabRANKMOAB
MatrixMetalloproteinaseInhibitor
StimulateOsteoclastActivityRANK:Osteoclast
ImprovesBoneDensity
OsteoporosisBoneMetastasis
DecreasesBonyComplicationsDecreasesCalcium
JawNecrosis
Drug DrugClass MechanismofAction Indications AdverseEffects ContraindicationsLapatinib Her-2TyrosineKinaseInhibitor BreastCancerGefitinibErlotinib
Non-Her-2TyrosineKinaseInhibitor
LungCancer
SunitinibSorafinib VEGFTyrosineKinaseInhibitor
RenalCellCarcinomaHepatoma
Hypothyroidism
ImatinibNilotinib Non-Cell-SurfaceReceptorTKI
InhibitstheTyrosineKinaseActivityoftheProteinProductoftheBCR/ABL/c-KIT
CML(BCR/ABL)GIST(c-KIT)
DiarrheaMyalgiaFluidRetention MutationoftheBCR/ABLGene
Vemurafenib B-RAFInhibitorInhibitsMutatedB-RAFProteinKinase
InhibitsRASPathwayMetastaticMelanoma
AnthralgiasFatigue
Rash--SquamousCellCancer
IfRASisTurnedon,itBypassestheMOABPathway,sothosedrugswillnotwork.
Drug DrugClass MechanismofAction Indications AdverseEffects ContraindicationsRapamycinSirolimus M-TORInhibitor
InhibitorofM-TORUnknownMechanismofAction
KidneyCancers
Drug DrugClass MechanismofAction Indications AdverseEffects ContraindicationsInterferon
AcuteToxicity SubacuteToxicity ChronicToxicityTOXICITIES
AlopeciaPredictable(3WeeksAfter1stCycle)
SeeninAnthracyclines,Taxanes,andsomeAlkylatingAgents
HairContinuestoGrow,butitisBrittleRe-GrowsoftenDifferentinTexture
Treatment:NoneColdCap(Ineffective)
MayDecreaseEfficacyAvoidConcurrentToxinsVaryDrugs
NeurologicalToxicity:SeenwithVincaAlkaloids
Taxanes&Platinum----------------
Sensory:Reversible+CommonMotor:Irreversible+Late
Autonomic:Unpredictable(GI)
OverexpressionofTelomerase:MemoryLoss(ChemoBrian)
FatigueChronicPainAging(LossofMuscleMass,GaitProblems)
NauseaandVomiting:WorseinYoungthanElderly
SeeninPlatinum,Anthracyclines,IVNitrogenMustardDerivedAlkylators
LargePsychologicalComponentUsedtobetheMainCauseofPre-MaturelyDiscontinuing
ChemoPrevention:LightMealsAmnesics
MultipleDrugsActiveDrugs:
HT-3Inhibitors(Ondansetron/Granesetron)Anti-Histamines(Prochloroperazine )
Anti-DopamineDrug(Metoclopromide )-ParkinsonianSideEffect
MinorTranquilizers(Lorazepam)Steroids(Dexamethasone )
THC--------------------------------------------------------------
Aprepitant(Emend):BlocksNeurokinin-1
(DoFinPatientswithNauseaDespiteHT-3Inhibitors)
CardiacToxicity:Anthracyclines:
Dose-DependentCardiomyopathyFree-RadicalMediated
WorsewithHypertensionorRadiationPreventedby:Dexrazoxane
(CardioprotecticeAgent)-------------------------------------------
Trastuzumab:Anti-HER2EffectonHeart
--------------------------------------CANNOTUSEANTHRACYCLINESAND
TRASTUZUMABTOGETHERPrevention:
MonitoringofDoseBaseline/Follow-UpCardiacEjection
Pregnancy:AllAgentshaveIncreasedRiskintheFIRSTTrimesterPatientsin2nd/3rdcanbeTreatewithMostAgents
NOTANTI-METABOLITES
CSFSupport:GranylocyteColonStimulating
Factor(GMCSF):UsedProphylactically
DecreasesInfection-RelatedHospitalizationandDeath
CausesBonePain-----------------Erythropoitin:
IncreasesRBCMassDecreasesBloodTransfusion
RequirementVERYImportantifTransfusionis
Unacceptable(Religion)---------------
MegakaryocyteGrowthFactor:(Thrombopoietin)
ReallyStillinDevelopment(EltromboprgApprovedforITP,
NotLowPlatelets)
Myelosuppression:MostImportantSideEffect
BiggestCauseofRx-RelatedDeathsPredictabletoaDegree:
WhiteCountDecreasesby7-10DaysPlateletsaBitLater
RedCellsDecreaseby1%PerDayOftenAssociatedwithSevereMucositisCreatinga
"PerfectStorm"forInfectionTreatment:AvoidCrowdsHand-Washing
ReportFeverorChillsImmediatelyIfLowAbsoluteNeutrophilCountwithFever
(RxImmediatelywithBroadSpectrumAntibiotics)IfFeverPersists,ConsiderFungalInfection
ForSubsequentCyclesConsiderDoseReduction,CSFSupportorBothPrevention:
UseofRelativelyLessMyelosuppressiveDrugs(Vincristine)
ChangeSchedule
Nephrotoxicity:SeeninCis-Platinum,Mitomycin-C,
Cyclophosphamide-----------------------Cis-Platinum:
Dose-DependentProximalTubuleToxinTreatwithAmifostine-------------------------Mitomycin-C:
CausesTTPwithRenalFailure-----------------------------
Cyclophosphamide+Isofosfamide:AcroleinMediatedHemorrhagic
CystitisTreatwithMESNA
ThromboembolicDisease:TAMOXIFEN
Trousseau'sSign------------------------------------
Osteoporosis:GiveCorticosteroids
Mucositis:SeeninAnti-Metabolites
UsuallyOccursatTimeofNadirBloodCountsOftenPainful,LeadingtoDysphagiaandDiarrhea
ResultsinElectrolyteDisturbanceandMalnutruitionAssociatedwithYeastInfectionandSepsis
Treatment:IntensiveMouthCare
Pre-RxDentalAssessmentMaintainGoodHydration
MouthWashContainingLocalAnaesthetic,Bicarbonate,Anti-FungalandOccasionalAnti-HistamineRequired.
DoseAdjustmentOccasionally,aFeedingTubeRequired.BarrierPreparationAvailable-Episil
PulmonaryToxicity:Bleomycin:
FreeRadicalIntermediatethatInteractswithHemeAssociatedIronin
PulmonaryInterstitum
HypothyroidismGonadalDysfunction
Anti-Metabolites:DiscolorationTaxanes:NailChanges
Capecitabine:Hand-FootEGFRInhibitors:AcneiformRash
SkinChanges:ExtravasationisBiggestConcern,ParticularlywithIV
Alkylators,NaturallyOccuringProducts.ConsideredanEmergency:
Treatment:DiscontinueInfusionIceandElevateLimb
Anti-InflammatoryandAnti-HistamineSystemicallyObservationtoAssessforExtensionofReaction
ConsultPlasticSurgery
DelayedHematologicToxicity:SeeninAlkylatorsandAnthracyclines
Presentation:MyelodysplasiaMyelofibrosisLeukemia(AML)
TTP
Oxaliplatin:PharyngolaryngealDysethesia
UsuallyTransientAggravatedbyColdAirorFluids
Vasculopathy:Anti-AngiogenesisDrugs
HypertensionProteinLosingNephropathyWoundHealingProblems
DiscontinueDrug/GiveACEInhibitorsIrinotecan:
InducesAcuteCholinergicSyndromeHypersalivation,AcuteDiarrhea,Bradycardia
TreatwithAtropine
Rasburicase:RecombinantUrateOxidase
AnEnzymethatMetabolizesUricAcidtoAllantoin
(AnInactiveMetaboliteofPurineMetabolism)
10xSolublethanUricAcidApprovedbyFDAforRxofTumorLysisSyndromeAssociatedwith
HematologicMalignancies
TumorLysisSyndrome:DuetoCellLysis
IncreasePotassium(Arrythmias)DecreasedCalcium(PhosphateLeavesCell,BindstoCa++)
IncreasedUricAcidMedicalEmergency:
IVFluidsAllopurinol
AttentiontoElectrolytesAllopurinol:
ChemoCausesBreakdownofCells+IncreaseinUricAcidThisPreventsAssociatedGoutBUTLeadstoEnhancedCytotoxicEffectofPurineAnaloguesandKidneyFailure
L-Asparaginase:Pancreatitis