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FOLFIRINOX

RegimenMonograph

RegimenName|DrugRegimen|CycleFrequency|PremedicationandSupportiveMeasures|DoseModifications|Adverse
Effects|Interactions|DrugAdministrationandSpecialPrecautions|RecommendedClinicalMonitoring|Administrative
Information|References|OtherNotes|Disclaimer

A-RegimenName

FOLFIRINOXRegimen
FolinicAcid(Leucovorin)-Fluorouracil-Irinotecan-Oxaliplatin

DiseaseSite Gastrointestinal-Pancreas

Intent Palliative

Regimen Evidence-Informed:
Category
Regimenisconsideredappropriateaspartofthestandardcareofpatients
meaningfullyimprovesoutcomes(survival,qualityoflife),tolerabilityorcosts
comparedtoalternatives(recommendedbytheDiseaseSiteTeamand
nationalconsensusbodye.g.pan-CanadianOncologyDrugReview,
pCODR).RecommendationisbasedonanappropriatelyconductedphaseIII
clinicaltrialrelevanttotheCanadiancontextOR(wherephaseIIItrialsarenot
feasible)anappropriatelysizedphaseIItrial.Regimenswhereoneormore
drugsarenotapprovedbyHealthCanadaforanyindicationwillbeidentified
underRationaleandUse.

Rationaleand First-linetreatmentoflocallyadvancedunresectableormetastaticpancreatic
Uses adenocarcinomainpatientswithECOGstatusof0to1andbilirubin<1.5x
ULN.Clinicaltrialsexcludedpatients>75yearsorwithsignificantcardiac
diseaseorpoororganfunction.

Note:FOLFIRINOXwillnotbefundedifapatienthaspreviouslyprogressedon
GEMCNPAC.

Supplementary oxaliplatin
PublicFunding NewDrugFundingProgram(OxaliplatinandIrinotecan-AdvancedPancreatic
Cancer(FOLFIRINOX))

irinotecan
NewDrugFundingProgram(Irinotecan(withOxaliplatin)-Metastatic
PancreaticAdenocarcinoma)

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B-DrugRegimen

oxaliplatin 85mg/m IVover2hours Day1


THEN,

leucovorin 400mg/m IVover2hours Day1


30minutesafterstartingleucovorin,give:

irinotecan 180mg/m IVover90minutes, Day1


concurrentlywithwith
leucovorin
fluorouracil* 400mg/m IVbolus,after Day1
THEN, leucovorin

fluorouracil 2400mg/m IVcontinuousinfusion StartonDay1


over46hours

*maybeomittediftoxicityofconcern

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C-CycleFrequency

REPEATEVERY14DAYS

Continueuntildiseaseprogressionorunacceptabletoxicityintheclinicaltrial12cycleswere
recommendedforrespondingpatients,whilethemediannumberofcycleswas10(range1-47).

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D-PremedicationandSupportiveMeasures

AntiemeticRegimen: Moderate

OtherSupportiveCare:

Irinotecan-Cholinergicadverseeffects(earlydiarrhea)
Unlesscontraindicated,atropine0.25-1mgIV/SCmaybegivenforcholinergicadverseeffects

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(earlydiarrhea)
Prophylacticatropinemaybeconsideredinpatientsexperiencingcholinergicsymptoms
Diarrhea(abdominalcramp=diarrhea)maybesevereanddelayedwithirinotecanuse
loperamide4mgattheonsetofdiarrhea,then2mgq2huntilpatientisdiarrhea-freefor12
hours

Filgrastimusemaybeconsideredassecondaryprophylaxisforneutropenia.

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E-DoseModifications

Dosesshouldbemodifiedaccordingtotheprotocolbywhichthepatientisbeingtreated.The
followingrecommendationshavebeenadaptedfromclinicaltrialsorproductmonographsandcould
beconsidered.

Dosagewithtoxicity

Donotstartnewcycleuntilplatelets75x109/LandANC1.5x109/L,recoveryfromdiarrhea(to
baselinewithoutloperamideforatleast24hours),andothernon-hematologictoxicitieshave
recoveredtograde2.

Dosesshouldbeadjustedbasedontheworstprecedingtoxicity.Donotre-escalatedoseifreduced
fortoxicity.Discontinuetheregimeniftoxicityrecursafter2dosereductions.

Leucovorindoseisnotreducedfortoxicityhoweveritshouldbeomittediffluorouracilisomitted.

DoseLevels:

Drug RegularDoselevel Doselevel-1 Doselevel-2


(mg/m2) (mg/m2) (mg/m2)
Irinotecan 180 150 --
Oxaliplatin 85 60 --
Fluorouracilbolus 400 300 200
Fluorouracilinfusion 2400 1800 1200

(Refertodosemodificationtableonthenextpage)

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DoseModifications:

Occurrence Irinotecana,b Oxaliplatina,b Flurouracila,b


Toxicity
Febrile 1st 1doselevel Nochange Discontinue
neutropeniaOR bolus
Grade4ANC>7d 2nd Asabove 1doselevel
OR
Delay1-2weeksfor
Grade1ANC
Thrombocytopenic 1st Nochange 1doselevel 1doselevel
bleedingOR
2nd 1doselevel Asabove 1further
grade3plateletsOR doselevelif
Grade3
Delay1-2weeksfor platelets
grade2platelets
Diarrheagrade3 1st 1doselevel Nochange Discontinue
OR bolus

Diarrheawithfeveror 2nd Asabove 1doselevel Asabove&


Grade3ANC 1doselevel

Grade3or4 - Nochange Nochange 1doselevel


mucositisorhand-foot
syndrome
Grade2persistent - Nochange 1doselevel Nochange
neurotoxicity
Grade2othernon- - Consider Consider Consider
hematological
Grade3neurotoxicity - Nochange 1doselevel Nochange
(recoverspriortonext
cycle)
Grade3othernon- - 1doselevel 1doselevel 1doselevel
hematological
Pneumonitis Any Discontinue Discontinue Discontinue
Grade3persistent Any Discontinue Discontinue Discontinue
neurotoxicity
OR
Grade4neurotoxicity

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Toxicity(Continued) Occurrence Irinotecana,b Oxaliplatina,b Flurouracila,b

Grade4othernon- Any Discontinue Discontinue Discontinue


hematological

OR

RPLS

OR

Hemolyticuremic
syndromeoranysigns
ofmicroangiopathic
hemolyticanemia
Pharyngolaryngeal - - infusionto6 -
dysesthesia hours
a
DonottreatuntilANC1.5x109/L,platelets75x109/L,diarrhearesolvedtobaselineandother
toxicitygrade2.Donotre-escalatedoseifreducedfortoxicity.
bDiscontinuetheregimeniftoxicityrecursafter2dosereductionsorifcycledelayedfor>2weeks.

HepaticImpairment

Transaminases Bilirubin^ Irinotecan Oxaliplatin 5FU


1-1.5XULNor Consider Nochange Nochange
Gilbert's
>3XULN* >1.5-4XULN Omit Nochange Nochange
>4XULN Omit Noinfofound Omit
*or5XULNwithlivermetastases

^Ifbilirubin,considerinvestigatingforreversiblecausessuchasbiliaryobstructionandreevaluate
afterstent.

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RenalImpairment

Creatinine oxaliplatin fluorouracil irinotecan


Clearance
(mL/min) (%previousdose) (%previousdose) (%previousdose)
>60 Nochange Nochange Nochange
>30- Caution Nochange Nochange
60
10-30 Discontinue Considerdose Caution
reduction
<10 Discontinue Considerdose Caution
reduction

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F-AdverseEffects

Refertooxaliplatin,leucovorin,irinotecan,fluorouracildrugmonograph(s)foradditionaldetailsof
adverseeffects

MostCommonSideEffects LessCommonSideEffects,butmaybe
SevereorLife-Threatening
Neuropathy(maybesevere)
Nausea/vomiting
Fatigue Arterialthromboembolism
Abdominalpain/cramping Hypersensitivity
Alopecia Cerebellarsyndrome
LFTs(maybesevere) GIobstruction
Diarrhea(earlyandlate,maybe GIperforation
severe) Cardiotoxicity
Anorexia Hemolyticuremicsyndrome
Mucositis Hepatotoxicity
Constipation Renalfailure
Edema Pancreatitis
Eyedisorders Pneumonitis
Myelosuppressioninfection, Rhabdomyolysis
bleeding(maybesevere) Seizure
Photosensitivity Venousthromboembolism
Rash
Hand-footsyndrome

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G-Interactions

Refertooxaliplatin,leucovorin,irinotecan,fluorouracildrugmonograph(s)foradditionaldetails

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H-DrugAdministrationandSpecialPrecautions

Refertooxaliplatin,leucovorin,irinotecan,fluorouracildrugmonograph(s)foradditionaldetails

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I-RecommendedClinicalMonitoring

RecommendedClinicalMonitoring

CBCbaselineandregular
Liverandrenalfunctiontestsbaselineandregular
Electrolytes,includingmagnesiumbaselineandregular
MonitorINRcloselyforpatientsonwarfarin
RoutinetoxicityratingofdiarrheaandotherGIeffects,cholingericsymptoms,
hypersensitivity,pneumonitis,bleeding,infection,dehydration,pancreatitis,
neurological,thromboembolism,hand-footsyndrome,cardiactoxicityandfatigue.

GradetoxicityusingthecurrentNCI-CTCAE(CommonTerminologyCriteriafor
AdverseEvents)version

SuggestedClinicalMonitoring

Bloodglucose,especiallyinpatientswithdiabetesBaselineandregular

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J-AdministrativeInformation

ApproximatePatientVisit 4.5hours

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PharmacyWorkload(averagetimepervisit) 44.043minutes
NursingWorkload(averagetimepervisit) 75.833minutes

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K-References

ConroyT,DesseigneF,YchouM,etal.FOLFIRINOXversusgemcitabineformetastaticpancreatic
cancer.NEnglJMed2011364:1817-25.

May2017re-linkNDFPform

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L-OtherNotes

Diarrheacanbesevere,witheitherimmediateordelayedonset.Patientsmustbeinstructed
intheuseofLoperamideastreatmentfordiarrhea,andmusthaveasupplyofthisdrugupon
startingIrinotecantreatments.

ThephaseIIIPRODIGE4/ACCORD11trial(Conroyetal.)hasdemonstratedsignificant
improvementinmedianoverallsurvival,medianPFSandobjectiveresponseascompared
togemcitabine.Despitethetoxicities,FOLFIRINOXhasshowngreaterclinicalbenefitthan
gemcitabinewhencoupledwithadequatepatientselectionandeffectivemanagementof
toxicsideeffects.

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M-Disclaimer

RefertotheNewDrugFundingProgramorOntarioPublicDrugProgramswebsitesforthemostup-to-datepublic
fundinginformation.

Theinformationsetoutinthedrugmonographs,regimenmonographs,appendicesandsymptommanagement
information(forhealthprofessionals)containedintheDrugFormulary(the"Formulary")isintendedforhealthcare
providersandistobeusedforinformationalpurposesonly.Theinformationisnotintendedtocoverallpossibleuses,
directions,precautions,druginteractionsoradverseeffectsofaparticulardrug,norshoulditbeconstruedtoindicate
thatuseofaparticulardrugissafe,appropriateoreffectiveforagivencondition.TheinformationintheFormularyis
notintendedtoconstituteorbeasubstituteformedicaladviceandshouldnotberelieduponinanysuchregard.All

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usesoftheFormularyaresubjecttoclinicaljudgmentandactualprescribingpatternsmaynotfollowtheinformation
providedintheFormulary.

Theformatandcontentofthedrugmonographs,regimenmonographs,appendicesandsymptommanagement
informationcontainedintheFormularywillchangeastheyarereviewedandrevisedonaperiodicbasis.Thedateof
lastrevisionwillbevisibleoneachpageofthemonographandregimen.Sincestandardsofusageareconstantly
evolving,itisadvisedthattheFormularynotbeusedasthesolesourceofinformation.Itisstronglyrecommended
thatoriginalreferencesorproductmonographbeconsultedpriortousingachemotherapyregimenforthefirsttime.

SomeFormularydocuments,suchasthemedicationinformationsheets,regimeninformationsheetsandsymptom
managementinformation(forpatients),areintendedforpatients.Patientsshouldalwaysconsultwiththeirhealthcare
provideriftheyhavequestionsregardinganyinformationsetoutintheFormularydocuments.

WhilecarehasbeentakeninthepreparationoftheinformationcontainedintheFormulary,suchinformationis
providedonanas-isbasis,withoutanyrepresentation,warranty,orcondition,whetherexpress,orimplied,statutory
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CCOandtheFormularyscontentprovidersshallhavenoliability,whetherdirect,indirect,consequential,contingent,
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