TIP

RegimenMonograph

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

A-RegimenName

TIPRegimen
Paclitaxel-Ifosfamide(withMesna)-Cisplatin

DiseaseSite Genitourinary-Testis

Intent Curative

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 Treatmentofrelapsedtesticulargermcelltumours.Thiswasstudiedina
Uses phaseIItrialinvolvingpatientswhofailedtoachieveacontinuousCRtoaprior
platinum-basedregimen,andhaveotherprognosticfeaturesforachievinga
favourableoutcometoconventional-dosecisplatin-basedsalvage
chemotherapy.

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B-DrugRegimen

PACLitaxel 250*mg/m IVover24hours Day1

*SomecentresgivepaclitaxelIVover3hours

mesna 500mg/m IVimmediatelybefore Days2to5

ifosfamide

ifosfamide 1500mg/m IVover1hour Days2to5

CISplatin 25mg/m IVover30minutes Days2to5

(Continuedonnextpage)

mesna 500**mg/m IVat4and8hours Days2to5

afterifosfamide
**(or1000mg/m2POat4and8hourspost-ifosfamide)

filgrastim 5mcg/kg SC Days7to18,until

ANC>1x10^9/L

OtherphaseI/IItrialsuseddifferentTIPdosingandschedules.Pleaserefertothereference
section.
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C-CycleFrequency

REPEATEVERY21DAYS

Foramaximumof4cycles,unlessdiseaseprogressionorunacceptabletoxicityoccurs

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D-PremedicationandSupportiveMeasures

AntiemeticRegimen: Moderate

FebrileNeutropenia High
Risk:

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OtherSupportiveCare:

Paclitaxel:Patientsshouldbepretreatedwithacorticosteroidaswellasanantihistamineand
aH2blocker:Forexample:
DEXAMETHASONE20mgPO12&6hoursor20mgIV30minutesbeforepaclitaxel
DIPHENHYDRAMINE50mgIV30minutesbeforepaclitaxel
RANITIDINE50mgIV30minutesbeforepaclitaxel

StandardregimensforCisplatinpremedicationandhydrationshouldbefollowed.RefertoCisplatin
monograph.

Ifosfamide:Oral/IVhydrationisstronglyencouraged.PoorlyhydratedpatientsmayneedmoreIV
hydration.Inadequatetotalhydrationmayresultindose-relatedhemorrhagiccystitis.

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E-DoseModifications

Dosesshouldbemodifiedaccordingtotheprotocolbywhichthepatientisbeingtreated.The
followingrecommendationshavebeenadaptedfromclinicaltrialsorproductmonographsandcould
beconsidered.
Seeappendix6forgeneralrecommendations.

Dosagewithtoxicity

Therewerenodosereductionsintheclinicaltrial.Recoveryfromtoxicitieswererequiredbeforere-
treatmentwithasubsequentcycle.

WorstToxicity PACLitaxel ifosfamide cisplatin

/Counts(x (%previousdose) (%previousdose) (%previous
9
10 /L)in dose)
previous
cycle
Somnolenceor 100% Holdmethylene 100%
othersignsof blue50mgIVq4h
encephalopathy until
resolution.Consider
prophylactic
methylenebluefor
subsequentcycles,
orconsider
discontinuingfor
nextcycle

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Hematuria 100% Holduntilresolution 100%
ifmicroscopicif
macroscopic
reducedoseor
discontinue
Grade3 Discontinue
neurotoxicity
Grade4related Discontinue
organ/non-
hematologic

*Intheclinicaltrial,re-treatmentwithasubsequentcyclerequiredaneutrophilcountof0.45x109 /Landaplateletcountof
75x109 /L.

Paclitaxel-DosageafterHypersensitivity:

Formildsymptoms(e.g.,mildflushing,rash,pruritus)itispossibletocompletetheinfusion
underclosesupervision.
Formoderatesymptoms(e.g.,moderaterash,flushing,milddyspnea,chestdiscomfort,mild
hypotension),
Stopthepaclitaxelinfusionandgivediphenhydramine25-50mgIVand
methylprednisolone125mgIV.
Oncesymptomshaveresolved,resumepaclitaxelinfusionatarateof10%oforiginal
ratefor15minutes,thenat25%oforiginalratefor15minutes,andifnofurther
symptomsdevelop,continueatoriginalrateuntilinfusioniscomplete.
Forseveresymptoms(e.g.,oneormoreof:respiratorydistressrequiringtreatment,
generalizedurticaria,angioedema,hypotensionrequiringtherapy),
Stopthepaclitaxelinfusiongivediphenhydramineandmethylprednisoloneasabove.
Useepinephrineorbronchodilatorsifindicated.
Donotrechallengewithpaclitaxel.

Filgrastim:HolddiscontinueforARDSoralveolarhemorrhage.

HepaticImpairment

Bilirubin AST/ALT PACLitaxel ifosfamide cisplatin

(% (%previous
previous dose)
dose)
1-2x and/or <2x 100% Nochange
ULN ULN
>2-4x and/or 2-5x to 75% Nochange

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ULN ULN 135mg/m2
>4xULN and/or >5x to Discontinue Nochange
ULN 50mg/m2or
omit

RenalImpairment

CreatinineClearance PACLitaxel ifosfamide cisplatin

(mL/min)
(%previousdose) (%previousdose) (%previousdose)
>60 Nochange 100% 100%
>45-60 Nochange 75% 75%
>30-45 Nochange 50% 50%
20-30 Nochange 50% Discontinue
<20 Nochange Discontinue Discontinue

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F-AdverseEffects

RefertoPACLitaxel,mesna,ifosfamide,CISplatin,filgrastimdrugmonograph(s)foradditional
detailsofadverseeffects

MostCommonSideEffects LessCommonSideEffects,butmaybe
SevereorLife-Threatening
Myelosuppressioninfection/ Hemolyticuremicsyndrome,vasculitis
bleeding(maybesevere) AML,MDS
Nauseaandvomiting Hypersensitivity(maybesevere)
Nephrotoxicity(maybesevere) Raynaud's
Electrolyteabnormalities Arrhythmia,cardiacfailure
Neurotoxicityandototoxicity(maybe Arterial,venousthromboembolism
severe) Pancreatitis
Hemorrhagiccystitis(maybesevere) GIperforation,obstruction
Diarrhea,mucositis Pneumonitis
Edema Seizure
Fatigue Encephalopathy
Myalgia,arthralgia Cardiotoxicity
IncreasesinLFTs(maybesevere) DIC
Alopecia SIADH
Rhabdomyolysis
Renaltubularacidosis/Fanconi
syndrome

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G-Interactions

RefertoPACLitaxel,mesna,ifosfamide,CISplatin,filgrastimdrugmonograph(s)foradditional
details

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H-DrugAdministrationandSpecialPrecautions

RefertoPACLitaxel,mesna,ifosfamide,CISplatin,filgrastimdrugmonograph(s)foradditional
details

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I-RecommendedClinicalMonitoring

RecommendedClinicalMonitoring

CBCbaselineandregular
Liverfunctiontestsbaselineandregular
Renalfunctiontests,baselineandregular
Urinalysis,forRBCsbeforeeachifosfamidedoseandregular
Electrolytes,includingmagnesium,phosphateandcalciumbaselineandregular
Bloodpressureandpulseratemonitoringduringinfusion,cardiacmonitoringwith
priorarrhythmia
Clinicaltoxicityassessment(infection,bleeding,musculoskeletalpain,
thromboembolism,cutaneouseffects,hypersensitivity,cystitis,nausea/vomiting,
neurotoxicity,ototoxicity)ateachvisit
Audiogramasclinicallyindicated
GradetoxicityusingthecurrentNCI-CTCAE(CommonTerminologyCriteriafor
AdverseEvents)version

SuggestedClinicalMonitoring

CBC2-3timesaweekduringfilgrastimtherapy

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J-AdministrativeInformation

ApproximatePatientVisit Day1:5hoursDays2-5:5.5hours
PharmacyWorkload(averagetimepervisit) 39.119minutes
NursingWorkload(averagetimepervisit) 53.167minutes

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K-References

KondaguntaGV,BacikJ,DonadioA,etal.Combinationofpaclitaxel,ifosfamide,andcisplatinisan
effectivesecond-linetherapyforpatientswithrelapsedtesticulargermcelltumors.JClinOncol
200523(27):6549-55.

MeadGM,CullenMH,HuddartR,etal.AphaseIItrialofTIP(paclitaxel,ifosfamideandcisplatin)
givenassecond-line(post-BEP)salvagechemotherapyforpatientswithmetastaticgermcell
cancer:amedicalresearchcounciltrial.BrJCancer200593(2):178-84.

MotzerRJ,SheinfeldJ,MazumdarM,etal.Paclitaxel,ifosfamide,andcisplatinsecond-linetherapy
forpatientswithrelapsedtesticulargermcellcancer.JClinOncol2000Jun18(12):2413-8.

April2016Replacedregimencategorywithevidence-informed

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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
usesoftheFormularyaresubjecttoclinicaljudgmentandactualprescribingpatternsmaynotfollowtheinformation
providedintheFormulary.

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

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thatoriginalreferencesorproductmonographbeconsultedpriortousingachemotherapyregimenforthefirsttime.

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

WhilecarehasbeentakeninthepreparationoftheinformationcontainedintheFormulary,suchinformationis
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