Analysis of the Incidence of Palmar-Plantar

ANALYSIS OF THE INCIDENCE OF PALMAR-PLANTAR ERYTHRODYSTHESIA AFTER THE ADMINISTRATION OF
®
DOCETAXEL/TAXOTERE USED AS AN ADJUVANT OR NEOADJUVANT BREAST CANCER THERAPY ON
PATIENTS RECEIVING A PREMEDICATION OF IV OR PER OS DEXAMETHASONE
Marie-Julie Roy1, Vanessa Blouin1, Isabelle Côté1 , Dr Julie Lemieux1,2, Anne Dionne1,2,3
1. Centre des maladies du sein Deschênes-Fabia- Hôpital du St-Sacrement - CHU de Québec- Université Laval
2. Centre de recherche du CHU de Québec – Axe Oncologie, Québec
3. Faculté de pharmacie, Université Laval, Québec
INTRODUCTION
Breastcancer:
• ThemostfrequentlydiagnosedcancerinCanada.
• Morethan1000newdiagnosisannuallyattheCentredesmaladies dusein
Deschênes-Fabia del’Hôpital duSt-Sacrement duCHUdeQuébec –
Université Laval.
Adjuvantchemotherapy:
• Docetaxel/Taxotere® isafrequentlyusedchemotherapyagentforadjuvant
breastcancertreatment.
• Adjuvantchemotherapyprotocolsare:FEC-D,TCandTcarbo.
Premedication:
• Docetaxel needstobeadministeredwithadexamethasonepremedication
takenorally(8mgx3doses)startingthenightbeforethetreatmentup
untilthetreatmentandafterthetreatment(8mgx3doses).Intravenous
(IV)dexamethasone(20mgx1dose)andafterthetreatment(8mgx3
doses)wasalsousedinourcenterafterthepublicationofthestudyby
Chouan etal. inordertoensureabettertreatmentadherence1.
BACKGROUND
Docetaxel andpalmar-plantarerythrodysthesia (PPE)
• Cutaneousreactionscanoccurunderdocetaxel (erythema,
cutaneouseruptionsandPPE)in50%ofthepatient(allgrades
included).Cutaneouseruptionswithdesquamationarereportedin
approximately5%ofthepatients2.Accordingtodifferentstudies,the
incidenceofPPEvariesfrom6-58%allgradesincluded,andfrom
0-4%forgradesIIIormore2-4.Thereis nomentionofPPEinstudies
conducted ondifferent docetaxel protocols inadjuvantbreast cancer
therapy5-6.TheauthorsofthestudyevaluatingTCarbo reportedan
incidenceof0%ofPPEwiththeirpatients7.Chouan etaldidnot
reportadifferenceintheincidenceofPPEdependingonthe
dexamethasonepremedicationregimen(POorIV)1.Astudy
conducted atour centercompared theincidenceofPPEinperos
dexamethasone regimen versusIVregimen andshowed anincidence
ofPPEof0%and10%respectively8.
OBJECTIVES
• TocomparetheincidenceofPPEgradeII-IIIonpatientswhowere
administeredapremedicationoforalorintravenousdexamethasone
whilereceivingdocetaxel chemotherapyintheadjuvantor
neoadjuvant treatmentofbreastcancer.
• ToassessthenumberofpatientswithconsequencesrelatedtoPPE
(treatmentpostponement,dosereduction,discontinuationof
treatmentandtreatmentmodification)
• Toassesstheproportionofpatientswhoneededatreatment
modificationoratreatmentdiscontinuationbecauseofPPE.
METHODS
Study design: Descriptive transversal study
Study population: Eligibility criteria
• Patientswhoreceivedadocetaxel chemotherapy,adjuvantor
neoadjuvant,(FEC-D,TC,TCarboH)totreatbreastcancerattheCentre
desmaladiesdusein Deschênes-Fabia del’Hôpital duSt-Sacrement du
CHUdeQuébec– Université Lavalbetweenapril 1st 2012andmarch
31st 2014.
Retrospectivedatacollection
Studyvariables:
• Premedication:
o Dexamethasonetakenorally8mgx3doses (nightbefore,
morning and1hour before treatment)
o DexamethasoneIV20mgx1dose
• PPEgradation
o GradeII:rednessandswellingwithpain onhandsorfeet
without affectingdailyactivities
o GradeIII:rednessandswellingwithintensepain on
handsorfeetaffectingdailyactivities
RESULTS
DISCUSSION
• Thecharacteristicsofthetwogroupsarecomparable
exceptfortheHER2Neustatusandthepresenceof
lymphovascular invasion.Wedonotbelievethat
thesedifferencesalonecanexplaintheobtained
results.
• ThereismorePPEaftercycle2forpatientswho
receivedIVdexamethasonecomparedtoPeros
dexamethasoneforallstudiedgrades(IIandIII).
MorepatientswhoreceivedIVdexamethasonehad
consequencesinrelativetotheirtreatment.Results
remainsignificantwhenthepatientswhochanged
premedicationregimenduringtheirtreatmentare
excluded.Samewiththepatientswhohaddose
modificationsortreatmentpostponements.
• Aftercycle3,thegroupsbecamesmaller,andit
beganhardertodrawconclusions.Thisimportant
diminutionisbecausepatientswhoreceivedFEC-D
didnothaveenoughcollectedinformationintheir
patients’fileaftercycle3tobeincludedforfurther
analysis.
• Theretrospectivestudydesignexplainstheabove
threeweaknesses.
• 4%ofthepatientsintheIVdexamethasonegroup
hadtodiscontinuetreatmentormodifythe
chemotherapyregimenvs0%inthePeros
dexamethasoneregimen.Thisanalysisisdescriptive
andtherefore,noconclusioncanbydrawnfromit.
Although,acertainpreoccupationarosefromthe
resultsbecausethesepatientsaretreatedinan
adjuvantcontext.
• Thereseemstobeacumulativeeffectofthecycles
becausethePPEappearsonlyatcycle2.The
mechanismexplainingtheaugmentationofthePPE
inrelationtotherouteofadministrationofthe
dexamethasoneisunknown.Theanti-inflammatory
effectofdexamethasonePeros maybe more
importantsinceitisadministeredatleast12hours
beforetheadministrationofdocetaxel.
CONCLUSION
Theobtainedresultsledustoreintroducetheuseof
dexamethasonePeros asthestandardpremedicationwith
docetaxel chemotherapy.DexamethasoneIVshouldbe
usedasanoptionwhennonobservanceoccurs,until
furtherinformationisavailable.
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