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Learning about

ColorectalCancer

A Personalized TreatmentGuide for Patients

Colorectal CancerAssociation of Canada

AvastinisatrademarkofGenentech,Inc.,Usedunderlicence.CamptosarisaregisteredtrademarkYakultHonshaCompany,Ltd.Eloxatinisaregisteredtrademarksanofi-aventisCanadaInc.Erbituxisatrademark(TM)ofImCloneLLC.VectibixisaregisteredtrademarkofAmgenManufacturing,Limited,asubsidiaryofAmgenInc.XelodaisaregisteredtrademarkofF.Hoffmann-LaRocheAG,usedunderlicense.

DISCLAIMER:Whileeveryefforthasbeenmadetoensureaccuracyinthisbookletastocurrentmedicalpractice inCanada,itcannotbefullycomprehensive.Individualneedsvaryandthebookletshouldnotbe usedasasubstituteforpropermedicalcare.

PublishedbyMultimed Incorporated.Copyright2011.AllRightsReserved.66MartinStreetMilton,ONL9T2R2Telephone:905875-2456Fax:905875-2864www .multi-med .com

ACKNOWLEDGEMENT:Fundingforthisguidewasgenerouslyprovidedthrough anunrestrictededucationalgrantfromSanofiCanadaInc.

Table of Contents

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2Knowing the Facts: Colorectal Cancer Statistics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3What is Colorectal Cancer? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3Stages and Grades of Colorectal Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4What are the Treatment Options? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 •Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 •RadiationTherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 •Chemotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 •TargetedTherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 BiomarkerTesting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 •HIPECtherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12Personalized Treatment SectionIntroduction: Combinations of chemotherapy and/or targeted therapy . . . . . . . . . . . . . . . . . . . . . . . . 13 •5-FU/Leucovorin/Oxaliplatin(FOLFOX-4) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 •Modified5-FU/Leucovorin/Oxaliplatin(modFOLFOX-6) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 •5-FU/Leucovorin/Oxaliplatin(FOLFOX-6) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 •5-FU/Leucovorin/Oxaliplatin+Bevacizumab(FOLFOX(any)+Bevacizumab) . . . . . . . . . . . . . . . . . . . . 20 •5-FU/Leucovorin/Oxaliplatin+Cetuximab(FOLFOX(any)+Cetuximab) . . . . . . . . . . . . . . . . . . . . . . . . 22 •5-FU/Irinotecan/Leucovorin(FOLFIRI) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 •5-FU/Irinotecan/Leucovorin+Bevacizumab(FOLFIRI+Bevacizumab) . . . . . . . . . . . . . . . . . . . . . . . . . 26 •5-FU/Irinotecan/Leucovorin+Cetuximab(FOLFIRI+Cetuximab) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 •Fluorouracil(5-FU)+Leucovorin(orfolinicacid)(5-FU/LV) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 •Capecitabine(CAPECITABINE) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 •Capecitabine/Oxaliplatin(CAPOX/XELOX) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 •Capecitabine/Oxaliplatin+Bevacizumab(CAPOX/XELOX+Bevacizumab) . . . . . . . . . . . . . . . . . . . . . . 36 •Irinotecan/Oxaliplatine(IROX) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 •Irinotecan+Cetuximab(IRINOTECAN+Cetuximab) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 •Cetuximab(CETUXIMAB) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 •Panitumumab(PANITUMUMAB) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 •Capecitabine+Bevacizumab(CAPECITABINE+Bevacizumab) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 •5-FU/Leucovorin/Irinotecan/Oxaliplatin(FOLFOXIRI) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 •5-FU/Leucovorin/Irinotecan/Oxaliplatin+Bevacizumab(FOLFOXIRI+Bevacizumab) . . . . . . . . . . . . . . 50 •Irinotecan/Capecitabine/Oxaliplatin(IXO) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52Managing Side Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54Colorectal Cancer Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59Canadian Resources for Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66Ongoing Research and the Future of Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69Where to Find Support . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69


1


3

Knowing the Facts: Colorectal Cancer Statistics

CRCisthesecondleadingcauseofdeathfromcancerinCanadainbothmenandwomen combined.CRChasasignificantimpactondeathformenandwomencombined.Thisyear anestimated22,200CanadianswillbediagnosedwithCRCand8,900willdiefromit. MorethanhalfofallnewcasesofCRCwillbediagnosedinpeople70yearsofageand older.Itisestimatedthat:1-3

•9,700womenwillbediagnosedwithCRCand3,900willdieofit•12,500menwillbediagnosedwithCRCand5,000willdieofit•Onaverage,426CanadianswillbediagnosedwithCRCeveryweek•Onaverage,171CanadianswilldieofCRCeveryweek

WhatarethechancesofgettingordyingfromCRC?1-3

•Inmen:1in14isexpectedtodevelopCRCduringtheirlifetimeand1in27willdieofit•Inwomen:1in15isexpectedtodevelopCRCduringtheirlifetimeand1in31willdieofit•Overall,colorectal canceristhesecond-leadingcauseofcancerdeathinCanada•DeathfromCRCcontinuestodeclineinbothmenandwomendue

toimprovementsintreatments,especiallychemotherapy.Screening forCRCcanlowertheriskofgettingitanddyingfromit

What is Colorectal Cancer?

Cancersthatstartinthecellsthatlinetheinsideofthecolon(thelongest partofthelargeintestine)andrectum(thelastfewinchesofthelarge intestinebeforetheanus)arecalledcolorectalcancers(CRCs).Thecolon andrectumformthelargeintestine(largebowel),whichisthelastportion ofthedigestivesystem.Thedigestivesystem,whichismadeupofthe esophagus,stomach,smallandlargeintestines,extractsandprocesses nutrients(vitamins,minerals,carbohydrates,fatsandproteins)from foodandhelpspasswastematerialoutofthebody.2,4

TheimportantnewsaboutCRCisthatitusuallystartsfroma pre-cancerousgrowthcalledapolypandgrowsslowly,usually inapredictableway.Itthereforecanbepreventablewithscreening, andwhendiagnosedatanearlystage,itisoftencurable.2

Learning About Colorectal Cancer: A Personalized Treatment Guide for Patients

Introduction

WelcometoLearning About Colorectal Cancer – A Personalized Treatment Guide for Patients.

Thegoalofthisguideishelpyoulearnaboutcolorectal cancer (CRC),diagnosis, treatmentsoptionsavailabletoyou,strategiestohelpyoumanagethediseasewhilemaintainingyourwell-being,andwheretofindsupportinyourarea.

Colour-coded,Personalized Treatment Sectioncontainsinformationondifferent combinationsofchemotherapyand/ortargeted therapyusedtotreatCRC.Theguide alsodiscussescurrentresearchandlooksatfuturetherapiesinCRC .

Foryourconvenience,youcanfindaGlossaryattheendofthisbooklet,tohelpyou betterunderstandthemedicalterminologyusedinCRC.Thewordsintheguidemarked initalicscanbefoundintheGlossary .

Thecontentsofthisguidehavebeenindependentlyreviewedandapprovedbythe appropriatemedicallyqualifiedexperts.

Screening for

CRC can reduce

both occurrence

and death.

2

CRC grows in a

predictable way, and

when diagnosed at

an early stage, it is

often curable.2


5

Stages and Grades of Colorectal Cancer

OnceaCRCdiagnosisismade,thecancerisusuallydescribedbyastageandgrade.

CRCstagingdescribesthesizeofthetumour,howfarithasgrownintothecolonorrectumwall,andwhetherthecancerhasspreadtolymph nodesorotherplacesinthebodypasttheplacewhereitfirstbegantogrow.CRCisdescribedbythefollowing5stages:1-2,4-5

Stage Description

0 Theabnormalcellsarefoundonlyintheinnermostlayer(mucosa)ofthecolonorrectum.Theseabnormalcellsmaybecomecancerousandspread.Stage0CRCisalsocalledcarcinoma in situ .

I Thetumour(cancer)hasgrownintotheinnerwallofthecolonorrectum,buthasnotgrownthroughthewall.

II Thetumour(cancer)hasgrownmoredeeplyintoorthroughthewallcolonorrectum,andmayinvadenearbytissuesbuthasnotspreadtothelymph nodes .

III Cancerinvolvesthenearbylymph nodes,butnottootherpartsofthebody.

IV Cancerhasspreadtootherpartsofthebody,suchastheliverorlungs.

4

Cancerthathasbeentreatedandhascomebackafteraperiodoftimewhenthecancercouldnotbedetectediscalledrecurrence.Thecancermaycomebackinthecolonorrectum,orinanotherpartofthebody.1-2,4-5

Inadditiontothecancerstage,itisalsousefultodeterminethegradeofthecancer,whichisdonebyexaminingabiopsysamplefromthetumourunderamicroscope.Examininghowthecancer cellslookandbehaveincomparisontonormalcellswillhelpdeterminethegradeofthecancer,andenableyourdoctortoestimatehowquicklythecancermaybegrowing.CRChasthreegrades:1-2,4-5

Grade Description

1 (Low) Cancerisslowgrowing,alsoreferredtoaswelldifferentiated

2 (Moderate) Cancerisintermediategrowing,alsoknownasintermediatedifferentiation

3 (High) Cancerisfastergrowing,alsoreferredtoaspoorlydifferentiated

What are the Treatment Options?

Yourtreatmentwilldependonyourgeneralhealthaswellasthetype,stageandgradeofthecancer.ForCRC,yourtreatmentmayincludeacombinationofsurgery, radiation therapy, chemotherapyandtargeted therapy . Workingtogetherwithyourhealthcareteam,youwilldecidewhattreatmentswillbebestforyou.Youmaybeinvitedtotakepartinaclinical trialtotestnewertreatmentoptionsorcombinations.1-2

AvailabletreatmentsforCRCaredescribedbelow.

Treatment option: Surgery

SurgeryisthemaintreatmentforCRC.Surgeryisusedtocurethecancerintheearlystagesbycompletelyremovingthetumourandtissuesaffectedbyit.It’soccasionallypossiblethatsurgerymayalsobeofferedtopeoplewhosetumourshavereturnedinthepelvisorspreadtotheliverorthelungs.Forpeoplewithdiseasethatcannotberemovedintotal,surgerymaybeofferedtohelprelievethesymptomsofcancer .1-2

Thesizeofthetumouranditslocation(whereitisintheintestine)willdeterminewhichsurgeryisrightforyou.1-2

Differentsurgicalproceduresareusedtoremovetumoursdependingontheirsize,location,howfartheyhavegrownintothewallofthecolonorrectum,andtheamountofcolonorrectumthatneedstoberemoved.Forremovalofsmallearlycancerssuchascancerouspolyps,atube(orscope)isinsertedthroughtherectum,whileforlargertumoursremovalofthepartoftheintestinecontainingthecancerisusuallynecessary.Ifapartoftheintestineisremoved,theremaininghealthypartsoftheintestinearesewntogether.Ifthiscan’tbedoneimmediately,atemporarycolostomymaybeperformedwhereanopeningwillbemadeintheabdomenandthecolonwillbepulledthroughthisopeningtotheoutsideofthebody.Thiswillhelpthebodypassthewastedirectlyfromthecolonthroughtheopeningintheskinandintoabag,whichcanbeemptiedregularly.Becauseeverypatientisdifferent,forsomeacolostomymaybepermanentwhileforothersitmayonlybeneededuntil

Treatment for

CRC will primarily

depend on its

stage. Knowing

the stage and

grade of the cancer

can help you and

your healthcare

team decide which

treatment is best

for you.1-2, 3-5

Source of illustration: C3Life.com, a website supported by Hollister Incorporated

radiationoncologistcandeliverhighdosesofthecancer-killingradiationmoresafelyforrectalcancers eitherbeforeoraftersurgery.Itisfollowingthedetailedpathologyanalysisofrectalcancersthatadecisionabouttheneedforradiationisusuallyreached.1-2

Possiblesideeffectsthatmaybeexperiencedafterradiationtreatmentincludefeelingofbeingmoretired thanusual,occasionaldiarrhea,andperhapschangestotheskinsuchasrednessortendernessinthearea ofthebodywherethetreatmentwasapplied.Thesesideeffectsaretemporaryandwillusuallygoaway whenthetreatmentperiodisoverandthenormalcellshavehadthechancetorepairthemselvesandusuallywithin1-2weeks.1-2

Treatment option: Chemotherapy

Commonly,drugs(medications)areusuallyusedtotreatthedifferentstagesofCRC . Chemotherapyisthe useofanticancermedications,alsocalledchemotherapy drugs,thataretypicallygivenbyinjectionintoavein byintravenousorIV infusion,orsometimesaspills,todestroycancer cells .1-2,4-5

Whilechemotherapydrugsworktodestroycancer cellsandhelppreventcancer cellsfromgrowingandspreading,theyalsocandamagehealthycells,andmaycausesideeffects.However,damagetohealthy cellsistemporaryandtheywillrepairthemselvesafterthetreatmentstops.1-2,4-5

Someofthesideeffectsthatmaybeexperiencedincludenausea,vomiting,stomatitisormucositis(soreness inthemouth),lossofappetite,tiredness,alopecia(hairloss),diarrhea,neurotoxicity,anincreasedriskofinfection,andbleeding.Yourhealthcareteamwillcarefullymonitoranysideeffectsandprovidemedications thatareeffectiveinreducingthesymptoms.1-2,4-5

Chemotherapytreatmentmaybegivenbeforeoraftersurgeryorboth.Differenttypesofchemotherapy (neoadjuvant, adjuvant,andpalliative)aredescribedinthetablebelow:1-2,4-5

Timing of chemotherapy treatment Purpose

Beforesurgery

Neoadjuvant chemotherapy / chemoradiation therapy

Givenbeforesurgery(preoperative)todecreasetumour sizeandcontrollocalspreadChemoradiation therapyischemotherapycombinedwithradiation therapytoshrinkarectaltumour

Aftersurgery

Adjuvant chemotherapy Givenaftersurgery(post-surgical)todestroyanymicroscopiccancercellsleftbehindandthereforehelptoreducetheriskofthecancercomingback

Palliative chemotherapy GiventohelpslowdownandcontrolthecancerwhenthecancerhasspreadtodistantorgansThegoalistocontrolsymptomsandextendlifebutultimately,thecancerisnotcurable


7

therectumhealsandafterabout2-3monthsthecolostomycanberemoved(orreversed).Thehealthcareprofessionalteamwillteachthepatienthowtomanageacolostomy,whichwillallowthepatienttocontinuetoparticipateineverydayactivities.1-2

ForsomepatientswithCRCthathasspreadinalimitedwaytoanareasuchastheliver,specializedsurgerycalledpartial liver resection for colorectal liver metastasis,maybeanoptiontoremovelivermetastasesiftheyaresmallorfewinnumber.1-2

Upto30percentofpeoplemaybecuredifmetastasesinthelivercanbecompletelyremoved (orresected).6

Treatment option: Radiation therapy

Therearetwotypesofradiation therapythatcanbeused:external beam radiation therapyand,occasionally,brachytherapy.Inexternalbeamradiation,thebeamofradiationisaimeddirectlyatthetumour.Inbrachytherapy,radioactivematerialisplacedinsidethetumour,makingitpossibletotreatthecancerinaveryfocusedmanner.1-2,7-11

Duringradiation therapy(alsocalledradiotherapy),highdosesofaspecialtypeofenergy(radiation)areaimedattheareawherethecancerisgrowing,destroyingcellsandmakingitimpossibleforthemtogrowanddivide.Whileradiation therapydestroyscancercells,whichgrowuncontrollably,italsocandamagehealthycellsnearby.Thegoodnewsisthathealthycellsareabletorepairthemselvesafterthetherapyiscomplete.1-2,7-11

Radiochemotherapy(alsocalledchemoradiation)ischemotherapy(typically5-FUorcapecitabine)combinedwithradiation therapy.Itisusedbeforerectalcancersurgerytoimprovethechancesofbettertumourcontrol,andreducelocalrecurrences(cancerfromcomingback).1-2,7-11

WhileradiochemotherapyisastandardofcareinCanada,notallpatientswithrectalcancerareconsideredcandidatesforthistreatmentbeforesurgery.Forexample,patientswhoareatriskofseveresideeffectsfromthecombinedtherapywhichmightpreventsuccessfulsurgery,aregenerallyexcluded,andgivenradiationalone,aseitherstandardfractionationorshorter-courseradiotherapy .10

TworadiotherapyoptionsareavailableinCanada:short-course(25Gygiveninfivefractions)andlong-course(45Gygivenin25fractions).8,12-13Bothshort-courseradiationalone(25Gyinfivefractions)andlong-courseradiation therapycombinedwithchemotherapy(45–50Gyin25–28fractions)havebeenshowntobeeffectiveindecreasinglocalrecurrenceriskforrectalcancer .14

Radiation therapyisrarelyusedforcoloncancerbecausethecolonisquitemobileandcancers,evenwhenonthesurface,tendtopushawayfromnearbystructuresandthelocalriskofcontaminationbythecancerislow.Thesmallintestineisalsonearbyanditfurtherlimitsthetypesofradiationdosagethatmightbenecessary.1-2

However,theoppositeistruefortherectum,wherelocalspreadcanreadilycontaminatethesidewallofthepelvis.Inaddition,thesmallintestineisatasafedistance.Thismeansthatthe

6

Chemotherapy

Forprimarycoloncancer

Forpeopleathighriskforrecurrence(stage3andhigh-riskstage2coloncancer)

Themostcommonchemotherapycombinationusedasadjuvant therapyisFOLFOX: LV(folinicacid)(Leucovorin®),fluorouracil(5-FU,Adrucil®),oxaliplatin(Eloxatin®)givenintravenouslyeverytwoweeksforaplannedtotalof12treatments

ForpeoplewhoarenotabletotoleratetheFOLFOXtreatmentregimen

Oralcapecitabine(Xeloda®)(thisis5-FUinpillform,whichistakentwicedailyfor2ofevery 3weeks,foraplannedtotalof24weeks.

ForadvancedormetastaticCRC

Themostcommonchemotherapycombinationsusedtotreatadvancedormetastatic CRC

1.FOLFOX:LV(folinicacid)(Leucovorin®),fluorouracil(5-FU,Adrucil®),oxaliplatin (Eloxatin®)+/-BEV

2.FOLFIRI:LV(folinicacid)(Leucovorin®),fluorouracil(5-FU,Adrucil®),irinotecan (Camptosar®,CPT-11);+/-BEV

3 . Capecitabine(Xeloda®)takeninsteadof 5-FUcombinationtreatments+/-BEV

Forpeopleafterpreviouschemotherapy treatmentshavefailed

Cetuximab(Erbitux®),typeoftargeted therapy,maybetakenalone,orincombinationwithirinotecan,forthetreatmentofnon-mutated (wild type) KRAS metastatic CRC.

Secondorthirdtreatmentchoiceforpeopleforwhomfirstchoicetreatmentoptionsdidnotwork

Panitumumab(Vectibix®),typeoftargeted therapy inthesameclassascetuximab,alsousedforthetreatmentofpatientswithnon-mutatedKRAS aftertreatmentscontainingfluoropyrimidines,oxaliplatinoririnotecanhavefailed.

Allavailablechemotherapytherapieseitheraloneorincombinationforthetreatmentofdifferentstages ofCRCaredescribedinthePersonalized Treatment Sectionofthisguide.


9

Ifsurgicalremovalofthelivermetastasesissuccessful,additionalchemotherapyisusuallyrecommendedaftersurgery(alsosometimesreferredtoas‘pseudo’-adjuvant chemotherapy).1-2.4-5

Insomecases,chemotherapymayberecommendedbeforesurgerytotheliver,ifthecancer isonlyconfinedtotheliver.Thisapproachmaybeusedtohelpapersonwhoisaborderlinecandidateforsurgery,becauseofthesizeorlocationoftheliver metastases,tohavesuccessfulsurgeryaftertheCRC metastaseshavebeenreducedinsizebythechemotherapy .15,16

Thetypesofchemotherapydrugs,andcertainlythedosesandschedulesvaryforeachpatient,andthetreatmentplanwilldependonyouruniquesituation.1-2,4-5

Descriptionofallavailablechemotherapyand/ortargeted therapycombinationsforthetreatmentofdifferentstagesofCRCaredescribedinthePersonalized Treatment Sectionofthisguide.

ThemostcommonlyusedchemotherapydrugstotreatCRCarefluorouracil (5-FU)andleucovorin (LVorfolinicacid),whichisaddedtoincreasetheeffectivenessof5-FU. 5-FUhasbeenusedformanyyearsanditseffectivenessisproven.OtherdrugsusedtotreatCRCincludeoxaliplatin, irinotecan, capecitabine(thisis5-FUinpillform),bevacizumab(BEV),cetuximab,andpanitumumab.Otherthancapecitabine,whichisapillandistakenbymouth,allotherchemotherapydrugsaregivenintoavein(intravenouslyorIV)throughapump.Theregimeninvolvingcontinuousintravenous infusion,requiresthatpatientshaveacentralvenous(intoavein)accesscathetereitherwitha“port-a-cath”whichisavascularaccessdevicesurgicallyimplantedunderneaththeskinandconnectedtooneofthelargebloodvesselsinthechest,oraperipherallyinsertedcentralcatheter(PICC)whichisinsertedthroughaveininthearm.The5-FU infusionisthendeliveredthroughaportablechemotherapypumpathome(referredtoasahomeinfusion pump).Thispumpisverysmall,anditfitsintoapackthatcanbewornaroundthewaist.1-2,4-5,15

Chemotherapydrugsinterferewiththeabilityoffastgrowingcells(likecancer cells)todivideormultiply.Becausemostofbody’snormalcellsofanadultarenotactivelygrowing,theyarelessaffectedbychemotherapy,exceptforthoseofbonemarrow(wherethebloodcellsaremade),thehair,andtheliningofthedigestivetract.Effectsofchemotherapyontheseandothernormaltissuescancausesideeffectssuchasnausea,hairloss,andtiredness.1-2,4-5

Thereareseveralchoicesofchemotherapyforbothprimaryandadvancedormetastatic CRC,whicharedecideduponindiscussionmainlywithyourmedicaloncologist,andtailoredspecificallytoyoursituation.1-2,4-5

8

As with all

chemotherapy

treatments you

may experience

side effects.

Because everyone

responds to

treatment

differently, your

side effects

may be different

as well. Talk to

your healthcare

team to learn ways

to manage these

side effects.1-2,4-5

Panitumumab (Vectibix®)

Panitumumab(Vectibix®),likecetuximab,alsotargetstheEGFR . Panitumumabisusuallyusedformetastatic CRC,afterotherdrugshavebeentriedanddidnotwork.Alsolikecetuximab,panitumumabiseffectiveonlyfortumoursthatdonothaveaspecificmutationintheKRAS gene.Formoreinformationontestingforbiomarkers,seesectiononBiomarker Testingofthisguide.15,20

Biomarker Testing

CRCisoneofthemostcommonlydiagnosedcancers.Recentscientificadvancesinhowitistreatedhavedramaticallyimprovedsurvival.OnesuchadvanceisabetterunderstandingofgenescalledKRASandBRAFwhichledresearcherstodevelopa waytopersonalizetreatmentforsomepatientswithmetastatic CRC .21

KRASandBRAFarebiomarkers,alsocalledmolecularmarkers,whicharebiologicalmoleculesfoundinblood,otherbodyfluids,ortissuesthatisasignofanormalorabnormalprocess,orofaconditionordisease.Atestforaparticularbiomarker,calledbiomarker testing,maybeusedtoseehowwellthebodyrespondstoatreatmentfor adiseaseorcondition.4

Biomarker testingisaformofpersonalizedapproachwhichistheoppositeofa“onesizefitsall”approachashasbeenusedbeforethediscoveryofbiomarkers.Withthe“onesizefitsall”approach,allpatientswiththesametypeandstageofCRCgotthesametreatment.However,thediscoveryofbiomarkerschangedthat,andnowresearchersknowthatnotwopatients’tumoursareexactlyalike.Knowingtheinformationaboutyourtumourcanhelpdoctorsdecidewhichtreatmentismorelikelytoworkthananother.21

KRAS and BRAF mutations

ResearchersfoundthatKRAS geneismutated(orchanged)inabout40%ofpeoplewithCRC.Theother60%ofpeoplewithCRChaveanon-mutated(alsocalledwild-type)KRAS gene.Abiomarkertest,alsoknownasKRAS mutationanalysis,or“KRAStesting”,whichisdoneonsampletissuefromtumoursremovedduringsurgery,cantellifthetumourhasthismutation .21

Itisrecommendedthatallpatientswithmetastatic CRCgettestedfortheKRAS mutation.IfKRAS mutationisfound,thenpatientsshouldnotbetreatedwithcetuximab (Erbitux®)orpanitumumab(Vectibix®).ThesedrugsdonotworkintumoursthathavetheKRAS mutation.However,notallpeoplewiththenon-mutated(alsocalledwild-type)KRAS tumoursrespondwelltotreatmentwithcetuximaborpanitumumabeither.Othertumourmarkersmaybepresentthancangiveadditionalinformationastowhattreatmentswillworkbestforthesepatients,buttheresearchinthisareaisstillongoing.21,22-23


11

Treatment option: Targeted therapy

Targeted therapyisanothertreatmentoptionavailabletohelptreatCRC . Targeted therapy drugsaredesignedtofindandattackspecificcancer cellswhiletryingnottoharmnormalcells . Monoclonal antibody therapyisatypeoftargeted therapyusedtotreatCRC.Thistypeoftherapyusesantibodiesmadeinthelaboratoryfromasingletypeofimmune system cell.Theseantibodiescanfindsubstancesoncancercellsornormalsubstancesthatmayhelpcancercellsgrow,sticktothesesubstancesanddestroythecancer cells,blocktheirgrowth,orstopthemfromspreading.1-2,4-5

Themostcommonlyavailabletargeted therapydrugoptionsincludebevacizumab(Avastin®),cetuximab(Erbitux®),andpanitumumab(Vectibix®),allofwhicharemonoclonal antibodies .17,19,20

Bevacizumab (Avastin®)

Bevacizumab(Avastin®)isoneofthetargeted therapydrugsusedforthetreatmentofmetastatic cancer ofthecolonandrectum.Bevacizumabtargetsthevascular endothelial growth factor (VEGF),whichisoneofthemainproteins(substances)madebycellsusedtohelpbuildbloodvesselsthatmakesmalltumourtogrowlarger.VEGFisimportantinthedevelopmentofabloodsupplyinagrowingtumourasthisbloodsupplyisessentialforthetumourtogrowandspread.BevacizumabworksbyattachingtoVEGFandstoppingbloodvesselsfromreachingatumour . Withoutbloodsupply,thetumourdies.Bevacizumabalsoimproveshowchemotherapydrugsworkbyhelpingcarrythesedrugsdirectlytothetumour . Bevacizumabisgenerallygivenincombinationwithotherdrugs,suchas5-FU, oxaliplatin, irinotecanandcapecitabine .17,18

Cetuximab (Erbitux®)

Cetuximab(Erbitux®)worksbytargetingaproteincalledtheepidermal growth factor receptor (EGFR)onthecancer cell . EGFRisfoundinabout80percentofCRCs.EGFRhelpscancer cells growandsurvivebytransmittingsignalstothesecells . Cetuximabattachestothesereceptors,whichcutsoffthissignaltransmissiontocancer cellsandcausesthesecellstodie.Cetuximab hasalsobeenshowntoworkevenifEGFRisnotfoundinanindividualtumour . Cetuximabdoesnotworkforallpatients.TheeffectivenessofcetuximabtreatmentwilldependonwhetherornotthetumourhasamutationintheKRAS gene.IfthetumourhastheKRAS mutation, cetuximabisnoteffective,butifthetumourdoesnothavetheKRAS mutation,cetuximabmaybeeffective.Cetuximabisactivewhengivenaloneorincombinationwithotherdrugs,likeirinotecan .2,15,19Formoreinformationontestingforbiomarkers,seesectiononBiomarker Testingofthisguide.

10

Description of

all available

chemotherapy

combinations with

bevacizumab,

cetuximab and

panitumumab for

the treatment of

different stages

of CRC are

described in the

Personalized

Treatment Section

of this guide

Talk to your doctor

about biomarker

testing to find a

treatment that is

right for you.

.

Talk to your

doctor about

biomarker

testing to find

a treatment

that is right

for you.

Personalized Treatment Section

Introduction: Combinations of chemotherapy and/or targeted therapy

Personalized Treatment Sectionofthisguidedescribesallavailablechemotherapyand/ortargeted therapyoptions,aloneorincombination,totreatCRC.Thissectionisdesignedtohelppatientstogo directlytospecificinformationrelatingtochemotherapyand/ortargeted therapycombinationrelatedto theirtreatment.Tohelpyounavigatethroughthissection,everydrugcombinationhasadifferentcolour, sothatyoucaneasilyfindthesectionofinterest,andreferbacktoit,justbylookingforthespecific colouronthetab.

Thefollowingchemotherapyand/ortargeted therapycombinationsaredescribedinthissection:

FOLFOX-4 CAPOX/XELOX modFOLFOX-6 CAPOX/XELOX+Bevacizumab FOLFOX-6 IROX FOLFOX(any)+Bevacizumab IRINOTECAN+Cetuximab FOLFOX(any)+Cetuximab CETUXIMAB FOLFIRI PANITUMUMAB FOLFIRI+Bevacizumab CAPECITABINE+Bevacizumab FOLFIRI+Cetuximab FOLFOXIRI 5-FU/LV FOLFOXIRI+Bevacizumab CAPECITABINE IXO

The side effects of combinations of chemotherapy and/or targeted therapy used to treat of CRC depend on the type, combination, and schedule of drugs used.


13

WhiletheabsenceofamutationintheKRAS genecanpredictthatapatientwillrespondtotreatmentwithcetuximaborpanitumumab,notallpatientswithnon-mutated(alsocalledwild-type)KRASrespondtotreatmentwiththesedrugs.Approximately5%to9%ofCRCshaveamutationinanothergenecalledBRAF .22-23

BRAF genemakesaproteincalledBRAF,whichisinvolvedinsendingsignalstocells,promotingcellgrowth.Thisgenemaybemutated(changed)inmanytypesofcancer,whichcausesachangeintheBRAF protein.Thiscanincreasethegrowthandspread(metastasis)ofcancer cells .4

PatientwhosetumourshaveBRAF mutations,alsomaynotrespondtotreatmentwithcetuximab orpanitumumab . BRAFtestingcanbeconsideredbutisnotyetrecommendedasastandardtestinallpatientswithCRC .22-23

Treatment option: HiPEC therapy

Hyperthermic Intraperitoneal ChemotherapyorHiPECisahighlyspecializedsurgicaltreatmentoptionusedforselectedpatientswhosecancershavespreadtotheliningsurfacesoftheperitoneal(abdominal)cavity(andnowhereelse),andareotherwisedifficulttotreatwithotheravailabletreatments.“Intraperitoneal”meansthatthetreatmentisdeliveredtotheabdominal cavity,and“hyperthermicchemotherapy”meansthatthesolutioncontainingchemotherapyisheatedtoatemperaturethatishigherthannormalbodytemperature.24

BeforereceivingHiPEC,thesurgeonwillremoveallvisibletumoursthatcanberemovedthroughouttheperitonealcavity.Afterthesurgery,whilestillintheoperatingroom,thesurgeonwillgivethepatientHiPECtreatment.DuringtheHiPECprocedure,thesurgeonwillcontinuouslyapplyaheatedsolutioncontainingachemotherapydrugthroughouttheperitonealcavity,foramaximumoftwohours(usually30minutesto90minutesdependingofwhichdrugsareused).TheHiPECprocedureisdesignedtohelpdestroyanycancercellsthatmaybeleftafterthesurgery.24

Thisprocedurealsoimprovesdrugabsorptionandeffectwithminimalexposuretotherestofthebody,whichhelpsavoidtheusualsideeffectsofchemotherapy . Oxaliplatinandmitomycin-C aresomeofthedrugsthatcanbeusedHiPEC therapy . HiPECsurgeryshouldonlybedoneincentresspecializedinperformingsuchproceduresandpatientsmustbecarefullyreviewedbyamultidisciplinaryteambeforeHiPECcanbeconsidered.24

12

Because drugs,

doses and

schedules may

vary from person

to person, your

doctor will decide

on the treatment

plan that is best

suited for you.

The side effects

will be different

depending on the

type of therapy.

Talk to your

healthcare

professionals

if you have any

questions or

concerns about

your treatments.

FOLFOX-4 treatment schedule27,28

FOLFOX-4 combination Treatment Schedule

Day 1 Oxaliplatin + LV:IV infusionover2hours followedby

5-FU:IV bolus followedby

5-FU:continuousIV infusionover22hours

Onceevery2weeksfor 12cyclesinadjuvantsetting.

Inthemetastaticsetting,thescheduledependsontheresponseortolerancetothetherapy .Day 2 LV:IV infusionover2hours

followedby5-FU:IV bolus followedby


What are the possible side effects?27-31

• Alopecia • Anemia • Diarrhea• Hepatotoxicity• Hypersensitivity • Nausea/vomiting• Neurotoxicity/neuropathy• Neutropenia • Stomatitis/mucositis• Thrombocytopenia

Please see the Glossary for definition of side effects appearing in italics. To help you manage your side effects, please see Managing Side Effects section.

Talk to your healthcare professional if you have these symptoms. This is not a complete list of side effects. If you have any unexpected effects while taking FOLFOX-4, contact your healthcare professional.

15

FOLF

OX

-4

5-FU/Leucovorin/Oxaliplatin (FOLFOX-4)

What is it?

FOLFOX-4isoneofseveralchemotherapycombinationsthatinclude5-fluorouracil (5-FU),leucovorin(LVorfolinicacid),andoxaliplatin.FOLFOXtreatmentschedulediffersindosingandadministrationscheduleofeachdrugandincludeFOLFOX-4,FOLFOX-6,modifiedFOLFOX-6(mFOLFOX-6),orothers.25-26

What is it used for?

Oxaliplatinplus5-FUandLV chemotherapycombinationorFOLFOX-4isusedisusedfortheadjuvanttreatmentofpatientswithstageIIorIIIcoloncanceraftertheyhaveundergoneasurgerytoremovethetumour,andformetastatic CRC .27

How is it given?

TheFOLFOX-4isgivenintoavein(intravenouslyorIV).27

How often is it given?

FOLFOX-4combinationisgivenevery2weeks.Everypatientisdifferent;yourdoctorwilldeterminewhatdoseisrightforyou.27

14

modFOLFOX-6 treatment schedule30

modFOLFOX-6 combination Treatment Schedule




Onceevery2weeksfor 12cyclesinadjuvantsetting.

Inthemetastaticsetting,thescheduledependsontheresponseortolerancetothetherapy .Day 2 5-FU:continuousIV infusionover24hours




Talk to your healthcare professional if you have these symptoms. This is not a complete list of side effects. If you have any unexpected effects while taking modFOLFOX-6, contact your healthcare professional.

17

mo

dFO

LFO

X-6

Modified 5-FU/Leucovorin/ Oxaliplatin (modFOLFOX-6)

What is it?

modFOLFOX-6isoneofseveralchemotherapycombinationsthatinclude5-fluorouracil (5-FU), leucovorin(LVorfolinicacid),andoxaliplatin.FOLFOXtreatmentscheduledifferindosingandadministrationscheduleofeachdrugandincludeFOLFOX-4,FOLFOX-6,modifiedFOLFOX-6(modFOLFOX-6),orothers.25-26


Oxaliplatinplus5-FUandLV chemotherapycombinationormodFOLFOX-6isusedforthe adjuvanttreatmentofpatientswithstageIIorIIIcoloncanceraftertheyhaveundergone asurgerytoremovethetumour,andformetastatic CRC .29-30

How is it given?

ThemodFOLFOX-6isgivenintoavein(intravenouslyorIV).29-30


modFOLFOX-6combinationisgivenonceevery2weeks.Everypatientisdifferent;yourdoctorwilldeterminewhatdoseisrightforyou.29-30

16

FOLFOX-6 treatment schedule31

FOLFOX-6 combination Treatment Schedule




Onceevery2weeks

Day 2 5-FU:continuousIV infusionover24hours




Talk to your healthcare professional if you have these symptoms. This is not a complete list of side effects. If you have any unexpected effects while taking FOLFOX-6, contact your healthcare professional.

19

FOLF

OX

-6

5-FU/Leucovorin/Oxaliplatin (FOLFOX-6)

What is it?

FOLFOX-6isoneofseveralchemotherapycombinationsthatinclude5-fluorouracil (5-FU), leucovorin(LVorfolinicacid),andoxaliplatin.FOLFOXtreatmentscheduledifferindosing andadministrationscheduleofeachdrugandincludeFOLFOX-4,FOLFOX-6,modified FOLFOX-6(modFOLFOX6),orothers.25-26


Oxaliplatinplus5-FUandLV chemotherapycombinationorFOLFOX-6isusedtotreatpeople withmetastatic CRC .31

How is it given?

TheFOLFOX-6isgivenintoavein(intravenouslyorIV).31


FOLFOX-6isgivenevery2weeksincombination.Everypatientisdifferent;yourdoctorwilldeterminewhatdoseisrightforyou.31

18

FOLFOX (any) + bevacizumab treatment schedule32-33

FOLFOX (any) + bevacizumab combination Treatment Schedule

Day 1 BevacizumabBEV:IV infusionover30-90minutesfollowedby

FOLFOXOxaliplatin:IV infusionover2hoursLV:IV infusionover2hours followedby

5-FU:IV bolus followedby continuousinfusionover22hours

Onceevery2weeks

Day 2* 5-FU:continuousIV infusionover22hours

*TreatmentonDay2willvarydependingontheFOLFOXcombination.


• Abdominal abscess• Alopecia • Anemia • Arterial thromboembolism• Diarrhea• Gastrointestinal perforation• Hepatotoxicity• Hypersensitivity • Hypertension • Nausea/vomiting• Neurotoxicity/neuropathy• Neutropenia • Proteinuria• Stomatitis/mucositis• Thrombocytopenia • Woundhealingcomplications


Talk to your healthcare professional if you have these symptoms. This is not a complete list of side effects. If you have any unexpected effects while taking FOLFOX (any) + bevacizumab, contact your healthcare professional.

21

FOLF

OX

(an

y) +

Bev

aciz

umab

5-FU/Leucovorin/Oxaliplatin + Bevacizumab (FOLFOX (any) + Bevacizumab)

What is it?

FOLFOXisoneofseveralchemotherapycombinationsthatinclude5-fluorouracil (5-FU), leucovorin(LVorfolinicacid),andoxaliplatin.FOLFOXtreatmentscheduledifferindosingandadministrationscheduleofeachdrugandincludeFOLFOX-4,FOLFOX-6,modifiedFOLFOX-6(modFOLFOX6),orothers.Bevacizumab (BEV)canbeaddedtoanyFOLFOXcombination.25-26

WhenaddedtoFOLFOX(any),BEVincreasesthechancesthatthetumourwillrespondtotreatmentandprolongssurvivalcomparedwithtreatmentwithoutbevacizumab . BEVtogetherwithFOLFOXisrecommendedinmostcasesasaofthefirst-lineorsecond-linetreatmentofmetastatic CRC .15


Oxaliplatinplus5-FUandLV chemotherapyorFOLFOX(any)incombinationwithBEVisused asfirst-lineorsecond-linetreatmentinpeoplewithmetastatic CRC .32

How is it given?

TheFOLFOX(any)+BEVcombinationisgivenintoavein(intravenouslyorIV).32


FOLFOX(any)+BEVcombinationisgivenevery2weeks.Everypatientisdifferent;your doctorwilldeterminewhatdoseisrightforyou.32-33

20

FOLFOX (any) + cetuximab treatment schedule34

FOLFOX (any) + cetuximab combination Treatment Schedule

Day 1 Cetuximab:IV infusionover2hoursfortheinitialdose.Afterthat,weeklydosesaregivenover1hour followedafter1hourbyFOLFOX

FOLFOXOxaliplatin + LV:IV infusionover2hours followedby



Onceevery2weeks

Day 2* 5-FU:continuousIV infusionover22hours

*TreatmentonDay2willvarydependingontheFOLFOXcombination.

What are the possible side effects?34

• Alopecia • Anemia • Diarrhea• Hepatotoxicity• Hypersensitivity • Infusion reactions• Nausea/vomiting• Neurotoxicity/neuropathy• Neutropenia • Skinreactions(rash,acne,itching,nailchanges,andinfusion-relatedreactions)• Stomatitis/mucositis• Thrombocytopenia


Talk to your healthcare professional if you have these symptoms. This is not a complete list of side effects. If you have any unexpected effects while taking FOLFOX (any) + cetuximab, contact your healthcare professional.

23

FOLF

OX

(an

y) +

Cet

uxim

ab

5-FU/Leucovorin/Oxaliplatin + Cetuximab (FOLFOX (any) + Cetuximab)

What is it?

FOLFOXisoneofseveralchemotherapycombinationsthatinclude5-fluorouracil (5-FU),leucovorin(LVorfolinicacid),andoxaliplatin.FOLFOXtreatmentscheduledifferindosing andadministrationscheduleofeachdrugandincludeFOLFOX-4,FOLFOX-6,modified FOLFOX-6(modFOLFOX6),orothers.CetuximabcanbeaddedtoanyFOLFOXcombination.25-26


FOLFOX(any)+cetuximabcombinationisusedtotreatpatientswithEGFR-expressing metastatic CRCwhosetumourshavewild-type(non-mutated)KRAS gene .34

How is it given?

FOLFOX(any)+cetuximabcombinationisgivenintoavein(intravenouslyorIV).34


FOLFOX(any)+cetuximabcombinationisgivenevery2weeks.Everypatientisdifferent; yourdoctorwilldeterminewhatdoseisrightforyou.34

22

FOLFIRI treatment schedule31

FOLFIRI combination Treatment Schedule

Day 1 LV:IV infusionover2hoursIrinotecan:IV infusionover90minutes followedby



Onceevery2weeks



• Alopecia• Anemia • Diarrhea• Hypersensitivity• Nausea/vomiting• Neutropenia • Stomatitis/mucositis • Thrombocytopenia


Talk to your healthcare professional if you have these symptoms. This is not a complete list of side effects. If you have any unexpected effects while taking FOLFIRI, contact your healthcare professional.

25

FOLF

IRI

5-FU/Irinotecan/Leucovorin (FOLFIRI)

What is it?

FOLFIRIisacombinationtherapyconsistingof5-fluorouracil (5-FU),irinotecan,andleucovorin (LVorfolinicacid).25-26


Irinotecanplus5-FUandLVcombinationchemotherapyregimensorFOLFIRImaybeconsideredforthetreatmentofadvancedormetastatic CRC .31

How is it given?

FOLFIRIisgivenintoavein(intravenouslyorIV).31


FOLFIRIisgiveneverytwoweeks.31

24

FOLFIRI + bevacizumab treatment schedule35

FOLFIRI + bevacizumab combination Treatment Schedule

Day 1 Bevacizumab BEV:IV infusionover90minutes followedbyFOLFIRI

FOLFIRI Irinotecan:IV infusionover90minutesLV:IV infusionover90minutes followedby



Onceevery2weeks



• Abdominal abscess• Alopecia• Anemia • Arterial thromboembolism• Diarrhea• Gastrointestinal perforation • Hypersensitivity• Hypertension• Nausea/vomiting• Neutropenia • Stomatitis/mucositis • Thrombocytopenia • Woundhealingcomplications


Talk to your healthcare professional if you have these symptoms. This is not a complete list of side effects. If you have any unexpected effects while taking FOLFIRI + bevacizumab, contact your healthcare professional.

27

FOLF

IRI +

Bev

aciz

umab

5-FU/Irinotecan/Leucovorin + Bevacizumab (FOLFIRI + Bevacizumab)

What is it?

FOLFIRI+bevacizumabisacombinationtherapyconsistingof5-fluorouracil (5-FU),irinotecan,leucovorin(LVorfolinicacid),andbevacizumab (BEV) .25-26


FOLFIRI+BEVcombinationisusedforthetreatmentofadvancedormetastatic CRC .35

How is it given?

FOLFIRI+BEVaregivenintoavein(intravenouslyorIV).35


FOLFIRI+BEVcombinationisgiveneverytwoweeks.35

26

FOLFIRI + cetuximab treatment schedule36

FOLFIRI + cetuximab combination Treatment Schedule

Day 1 Cetuximab:IV infusionover2hoursinitially, thenweeklyover1hour followedafteronehourbyFOLFIRI

Onceevery1or2weeks

Day 1 FOLFIRI Irinotecan:IV infusionover30-90minutes followedby

LV:IV infusionover2hours followedby





• Alopecia• Anemia • Diarrhea• Hypersensitivity• Infusion reactions• Nausea/vomiting• Neutropenia • Stomatitis/mucositis • Skinreactions(rash,acne,itching,nailchanges,andinfusion-relatedreactions)• Thrombocytopenia


Talk to your healthcare professional if you have these symptoms. This is not a complete list of side effects. If you have any unexpected effects while taking FOLFIRI + cetuximab, contact your healthcare professional.

29

FOLF

IRI +

Cet

uxim

ab

5-FU/Irinotecan/Leucovorin + Cetuximab (FOLFIRI + Cetuximab)

What is it?

FOLFIRI+cetuximabisacombinationtherapyconsistingof5-fluorouracil (5-FU),irinotecan,leucovorin(LVorfolinicacid),andcetuximab .25-26


Forpatientswithwild-type(non-mutated)KRAS gene,cetuximabisaddedtotheFOLFIRIcombinationtotreatadvancedormetastatic CRC .36

How is it given?

FOLFIRI+cetuximabcombinationisgivenintoavein(intravenouslyorIV).36


FOLFIRI+cetuximabcombinationisgivenevery2weeks.36

28

5-FU/LV treatment schedule27,37

5-FU/LV combination Treatment Schedule

Day 1 LV:IV infusionover2hours followedby



Onceevery2weeksfor12cyclesinadjuvantsetting.

Inthemetastaticsetting,thescheduledependsontheresponseortolerancetothetherapy .Day 2 LV:IV infusionover2hours

followedby5-FU:IV bolus followedby



• Alopecia• Anemia• Diarrhea• Nausea/vomiting• Neutropenia• Stomatitis/mucositis• Thrombocytopenia


Talk to your healthcare professional if you have these symptoms. This is not a complete list of side effects. If you have any unexpected effects while taking 5-FU/LV, contact your healthcare professional.

31

5-FU

/LV

Fluorouracil (5-FU) + Leucovorin (or folinic acid) (5-FU/LV)

What is it?

5-FU/LVisachemotherapycombinationoffluorouracil (5-FU)andleucovorin (LVorfolinicacid).25-26


ForpatientswhocannottolerateanaggressivechemotherapyregimenFOLFOX,XELOX, orFOLFIRIduetotheirage,physicalcondition,orothermedicalproblems,thereis anotheralternative.15

5-FU/LV chemotherapycombinationisalesstoxicalternative,whichisusedasadjuvant treatmentforpeoplewithstageIIorIIIcoloncanceraftertheyhaveundergoneasurgery toremovethetumour.Itisalsousedinthetreatmentofadvancedormetastatic CRC .27,37

How is it given?

5-FU/LVisgivenintoavein(intravenouslyorIV).27,37


5-FU/LVcombinationisgivenonceevery2weeks.Everypatientisdifferent;yourdoctor willdeterminewhatdoseisrightforyou.27,37

30

Capecitabine treatment schedule39

Capecitabine Treatment Schedule

Day 1-14 Capecitabine:Tabletstakentwiceaday(morningandeveningdoses)for14dayswithin30minutesaftertheendofameal(breakfastanddinner)

Takenin21daycycles-takecapecitabinefor14daysandthenstoptakingitfor7days,thenstartagain


• Anemia• Diarrhea• Hand-and-foot syndrome• Nausea/vomiting• Neutropenia • Stomatitis/mucositis• Thrombocytopenia


Talk to your healthcare professional if you have these symptoms. This is not a complete list of side effects. If you have any unexpected effects while taking capecitabine, contact your healthcare professional.

33

CAPE

CITA

BIN

E

Capecitabine (CAPECITABINE)

What is it?

ForpatientswhocannottolerateanaggressivechemotherapyregimenFOLFOX,XELOX, orFOLFIRIduetotheirage,physicalcondition,orothermedicalproblems,thereisanotheralternative,capecitabinealone.Capecitabineworksalmostaswellasanintravenous 5-fluorouracil (5-FU)plusleucovorin(LVorfolinicacid).25-26,38

Capecitabinebelongstoafamilyofmedicationscalledthefluoropyrimidines(medicationsthatinterferewiththegrowthofcellsthatrapidlydivideinthebody,includingcancer cells).Capecitabineisaninactivesubstanceonitsown.Whencapecitabineistaken,itischangedinthebody,mostlywithinthetumour(cancer cells),tobecomethecommonlyusedcancer medicationcalled5-FU.Insomepatients5-FUwillkillcancer cellsanddecreasethesize ofthetumour .15,38


CapecitabineisusedasadjuvanttreatmentforpeoplewithstageIIorIIIcoloncancerafter theyhaveundergoneasurgerytoremovethetumour.Itisalsousedinthetreatmentofadvancedormetastatic CRC.38,39

How is it given?

Capecitabineisavailableastabletsthataretakenbymouth,andswallowedwholewithwater.Yourdoctorwillcalculatethedoseforyou.Youmayneedtotakeacombinationof150mgand500mgtablets.Togettherightdoseitisveryimportantthatyouidentifythetabletscorrectlyeachtimeyoutakecapecitabine.Takingthewrongtabletscouldresultinanoverdose(too muchmedication)orunderdose(toolittlemedication).38


Capecitabinetabletsaretakentwiceadayfor14days.38,39

32

CAPOX/XELOX treatment schedule40

CAPOX/XELOX combination Treatment Schedule

Day 1 Oxaliplatin:IV infusionover2hours Onceevery3weeks



• Alopecia• Anemia• Diarrhea• Hand-and-foot syndrome• Hepatotoxicity • Nausea/vomiting• Neurotoxicity/neuropathy• Neutropenia • Stomatitis/mucositis• Thrombocytopenia


Talk to your healthcare professional if you have these symptoms. This is not a complete list of side effects. If you have any unexpected effects while taking CAPOX/XELOX, contact your healthcare professional.

35

CAPO

X/X

ELO

X

Capecitabine/Oxaliplatin (CAPOX/XELOX)

What is it?

CAPOX/XELOXisacombinationoftwoanticancerdrugs:capecitabineandoxaliplatin .25-26


CAPOX/XELOXisusedinadjuvanttreatmentofadvancedormetastatic CRCthathasspreadoutsideofthecolonand/orrectum.40

How is it given?

CAPOX/XELOXcombinationisgivenasanintravenous infusionofanoxaliplatinfollowed bycapecitabinetabletstakenbymouth.40


Capecitabinetabletsaretakentwiceaday,andoxaliplatinisinfusedonceevery3weeks.40

34

CAPOX/XELOX + bevacizumab treatment schedule41

CAPOX/XELOX + bevacizumab combination Treatment Schedule

Day 1 Oxaliplatin:IV infusionover2hoursBEV:IV infusionover90minutesthefirsttime,and30or60minutesafterthesecondorthirdtime

Onceevery3weeks

Capecitabineistakenin21daycycles-takecapecitabinefor 14daysandthenstoptakingitfor7days,thenstartagain



• Abdominal abscess • Alopecia• Anemia• Arterial thromboembolism• Diarrhea• Gastrointestinal perforation• Hand-and-foot syndrome• Hepatotoxicity • Hypertension • Nausea/vomiting• Neurotoxicity/neuropathy• Neutropenia • Stomatitis/mucositis• Thrombocytopenia• Woundhealingcomplications


Talk to your healthcare professional if you have these symptoms. This is not a complete list of side effects. If you have any unexpected effects while taking CAPOX/XELOX + bevacizumab, contact your healthcare professional.

37

CAPO

X/X

ELO

X +

Bev

aciz

umab

Capecitabine/Oxaliplatin + Bevacizumab (CAPOX/XELOX + Bevacizumab)

What is it?

CAPOX/XELOX+Bevacizumabisachemotherapycombinationofcapecitabine,oxaliplatin andbevacizumab (BEV) .25-26


CAPOX/XELOX+BEVcombinationisusedforadvancedormetastatic CRCthathasspreadoutsideofthecolonand/orrectum.41

How is it given?

OxaliplatinandBEVaregivenintoavein(intravenouslyorIV).Capecitabineisatablet andistakenbymouth.41


Capecitabinetabletsaretakentwiceaday,andoxaliplatinandBEVaregivenonceevery 3weeksintoaveinbyintravenous infusion .41

36

IROX treatment schedule43

IROX combination Treatment Schedule

Day 1 Oxaliplatin + irinotecan:IV bolus infusion Onceevery3weeks


• Diarrhea• Nausea/vomiting• Neurotoxicity/neuropathy• Neutropenia


Talk to your healthcare professional if you have these symptoms. This is not a complete list of side effects. If you have any unexpected effects while taking IROX, contact your healthcare professional.

39

IRO

X

Irinotecan/Oxaliplatin (IROX)

What is it?

IROXisachemotherapycombinationconsistingoftwodrugs,irinotecanandoxaliplatin .25-26


IROXisusedtotreatadvancedormetastatic CRCinpatientswhocannotuse5-fluoropyrimidine therapysuchas5-FUorcapecitabine .43

How is it given?

IROXisgivenintoavein(intravenouslyorIV).43


IROXisgivenonceevery3weeks.43

38

Irinotecan + Cetuximab treatment schedule19,44,45

Irinotecan + cetuximab combination Treatment Schedule

Day 1 Cetuximab:IV infusionover2hours followedby

Irinotecan:IV infusionover60-90minutes

Cetuximab:Onceeveryweek

Irinotecan:Onceevery2weeks

Ifyoureceiveirinotecanwithcetuximabinthesameweek,irinotecanwillbegivenaftertheendofthecetuximab infusion .

What are the possible side effects?19,44

• Anemia• Diarrhea• Hypersensitivity • Infusionreactions• Nausea/vomiting• Neutropenia• Skinreactions(rash,acne,itching,nailchanges,andinfusion-relatedreactions)• Stomatitis/mucositis• Thrombocytopenia


Talk to your healthcare professional if you have these symptoms. This is not a complete list of side effects. If you have any unexpected effects while taking Irinotecan + cetuximab, contact your healthcare professional.

41

IRIN

OTE

CAN

+ C

etux

imab

Irinotecan + Cetuximab (IRINOTECAN + Cetuximab)

What is it?

Irinotecan + cetuximabisachemotherapycombinationconsistingoftwoanticancerdrugs,irinotecanandcetuximab .25-26


Thiscombinationisusedforthetreatmentofnon-mutatedKRAS metastatic CRCin patientswhohavebeenresistanttootherchemotherapyregimenscontaining5-FU, irinotecanoroxaliplatin .19

How is it given?

Irinotecan + cetuximabaregivenintoavein(intravenouslyorIV).19


Irinotecan + cetuximabaregivenonceeveryweek.19,44

40

Cetuximab treatment schedule19

Cetuximab Treatment Schedule

Day 1 Cetuximab:IV infusionover2hours Onceeveryweek


• Diarrhea• Hypersensitivity• Infusion reactions• Skinreactions(rash,acne,itching,nailchanges,andinfusion-relatedreactions)


Talk to your healthcare professional if you have these symptoms. This is not a complete list of side effects. If you have any unexpected effects while taking cetuximab, contact your healthcare professional.

43

CETU

XIM

AB

Cetuximab (CETUXIMAB)

What is it?

Cetuximabisamonoclonal antibodythatspecificallyrecognizesandbindstotheepidermal growth factor receptor (EGFR)foundonthesurfaceofcertaintumour cells .19


CetuximabisusedtotreatEGFR-expressingmetastatic CRCwithnon-mutated(wild-type) KRASafterfailureofchemotherapyregimenscontainingfluoropyrimidine, oxaliplatin, andirinotecan .19

What does it do?

Cetuximabbindstotheepidermal growth factor receptor (EGFR)foundonthesurfaceof certaintumour cells,andasaresultofthisbinding,thetumour cellcannolongerreceive themessagesitneedsforgrowth,progressionandmetastasis .19

How is it given?

Cetuximabisgivenintoavein(intravenouslyorIV).19


Cetuximabaloneisgivenonceaweek.19

42

Panitumumab treatment schedule20

Panitumumab Treatment Schedule

Day 1 Panitumumab:IV infusionover1hour Onceevery2weeks


• Anemia• Diarrhea• Hypersensitivity• Skinrash


Talk to your healthcare professional if you have these symptoms. This is not a complete list of side effects. If you have any unexpected effects while taking panitumumab, contact your healthcare professional.

45

PAN

ITU

MU

MA

B

Panitumumab (PANITUMUMAB)

What is it?

Panitumumabisamonoclonal antibodythatrecognizesandattachestoCRC cellsthat expressepidermal growth factor receptor (EGFR) .20


PanitumumabisusedtotreatEGFR-expressingmetastatic CRCwithnon-mutated(wild-type)KRASafterfailureofchemotherapyregimenscontainingfluoropyrimidine, oxaliplatin, andirinotecan .20

What does it do?

PanitumumabrecognizesandattachestoCRC cellsthatexpressEGFR,preventing thecancer cellsfromgrowinganddividing.20

How is it given?

Panitumumabisgivenintoavein(intravenouslyorIV).20


Panitumumabisgivenonceeverytwoweeks.20

44

Capecitabine + bevacizumab treatment schedule42

Capecitabine + bevacizumab combination Treatment Schedule


Takentwicedailyonday1through14followedby7-dayrest,every3weeks

Day 1 Bevacizumab:IV infusionover90minutes(about30or60minutesafterthefirstorsecondtime)

Onceevery3weeks


• Abdominal abscess• Arterial thromboembolism• Diarrhea• Gastrointestinal perforation• Hand-and-foot syndrome • Hypersensitivity• Hypertension • Infusion reactions• Nausea/vomiting• Thrombocytopenia• Woundhealingcomplications


Talk to your healthcare professional if you have these symptoms. This is not a complete list of side effects. If you have any unexpected effects while taking Capecitabine + bevacizumab, contact your healthcare professional.

47

CAPE

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Bev

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umab

Capecitabine + Bevacizumab (CAPECITABINE + Bevacizumab)

What is it?

Capecitabine + bevacizumabisachemotherapycombinationcontainingcapecitabine andbevacizumab (BEV) .25-26


Capecitabine + BEVcombinationisusedtotreatmetastatic CRCthathasspreadoutside ofthecolonand/orrectum.42

How is it given?

Capecitabineisavailableastabletsthataretakenbymouth,andswallowedwhole withwater.BEVisgivenintoavein(intravenouslyorIV).42


Capecitabinetabletsaretakenwithin30minutesaftertheendofameal(breakfastand dinner),twiceaday(morningandeveningdoses),andBEVisgivenonceevery14days.42

46

FOLFOXIRI treatment schedule46

FOLFOXIRI combination Treatment Schedule

Day 1 Oxaliplatin + Irinotecan + LV:IV infusionover2hours followedby


Onceevery2weeks


• Anemia • Diarrhea• Nausea/vomiting• Neurotoxicity/neuropathy• Neutropenia• Stomatitis/mucositis• Thrombocytopenia


Talk to your healthcare professional if you have these symptoms. This is not a complete list of side effects. If you have any unexpected effects while taking FOLFOXIRI, contact your healthcare professional.

49

FOLF

OX

IRI

5-FU/Leucovorin/Irinotecan/ Oxaliplatin (FOLFOXIRI)

What is it?

FOLFOXIRIisachemotherapycombinationtreatmentcontaining5-fluorouracil (5-FU), leucovorin(LVorfolinicacid),irinotecanandoxaliplatin .25-26


FOLFOXIRIisusedtotreatadvancedormetastatic CRC .46

How is it given?

FOLFOXIRIisgivenintoavein(intravenouslyorIV).46


FOLFOXIRIisgivenevery2weeks.46

48

FOLFOXIRI + bevacizumab treatment schedule47

FOLFOXIRI + bevacizumab combination Treatment Schedule

Day 1 Bevacizumab BEV:IV infusion(firstinfusionover90minutes, secondinfusionover1hour,andsubsequentinfusionsover30minutes) followedbyFOLFOXIRI

FOLFOXIRIOxaliplatin + Irinotecan + LV:IV infusionover2hours followedby


Onceevery2weeks


• Abdominal abscess • Anemia • Arterial thromboembolism• Diarrhea• Gastrointestinal perforation• Hypertension • Nausea/vomiting• Neurotoxicity/neuropathy• Neutropenia• Stomatitis/mucositis• Thrombocytopenia• Woundhealingcomplications


Talk to your healthcare professional if you have these symptoms. This is not a complete list of side effects. If you have any unexpected effects while taking FOLFOXIRI + bevacizumab, contact your healthcare professional.

51

FOLF

OX

IRI +

Bev

aciz

umab

5-FU/Leucovorin/Irinotecan/ Oxaliplatin + Bevacizumab (FOLFOXIRI + Bevacizumab)

What is it?

FOLFOXIRI+bevacizumabisachemotherapycombinationtreatmentcontaining5-fluorouracil (5-FU), leucovorin(LVorfolinicacid),irinotecan,oxaliplatinandbevacizumab (BEV) .25-26


FOLFOXIRI+BEVcombinationisusedtotreatadvancedormetastatic CRC.AdditionofBEV toFOLFOXIRIcombinationincreasestreatmenteffectiveness.47

How is it given?

FOLFOXIRI+BEVcombinationisgivenintoavein(intravenouslyorIV).47


FOLFOXIRI+BEVisgivenonceevery2weeks.47

50

IXO treatment schedule28,48

IXO combination Treatment Schedule

Day 1 Oxaliplatin:IV infusionover2hoursfollowedby

Irinotecan:IV infusionover1hour

Onceevery3weeks


Capecitabineistakenin21daycycles-takecapecitabinefor 14daysandthenstoptakingitfor7days


• Anemia• Diarrhea• Nausea/vomiting• Neurotoxicity/neuropathy• Neutropenia


Talk to your healthcare professional if you have these symptoms. This is not a complete list of side effects. If you have any unexpected effects while taking IXO, contact your healthcare professional.

53

IXO

Irinotecan/Capecitabine/ Oxaliplatin (IXO)

What is it?

IXOisachemotherapydrugcombinationconsistingofirinotecan,capecitabine andoxaliplatin .25-26


IXOisusedtotreatmetastatic CRC .48

How is it given?

Capecitabineisavailableastabletsthataretakenbymouth,andswallowedwhole withwater.Irinotecanandoxaliplatinaregivenintoavein(intravenouslyorIV).48


Capecitabinetabletsaretakentwiceadayfor14days.Irinotecanandoxaliplatin areinfusedonceevery3weeks.48

52

Diarrhea:Avoidfoodshighinfibre(freshfruit,rawvegetables,wholegrains,bran,nuts,andseeds);Eatfrequentsmallmealsofcookedfruits/vegetables,rice,leanmeats,fishorchicken,bananas,applesauce,toast;Eliminatemilkandmilkproducts,caffeineandalcohol;Avoidgreasy,spicyorsugaryfoods;Drinkplentyoffluidsbyincreasingfluidintakeasmuchasyoucan(8-12eightozcups/day);Takeantidiarrhealmedicationsasprescribedbyyourhealthcareprofessionaloraccordingtopackageinstructions;Formoredietarytips,askyourhealthcareprofessionaltoreferyoutoadietician.Comfortmeasuresinclude:Sitzbaths(awarmwaterbathwherethewatercoversonlythehipsandbuttocks);Usesoothingwipes;Usehaemorrhoidbarriercreamsasneeded.

F

Fever:See“Neutropenia”.

Febrile neutropenia:See“Neutropenia”.

G

Gastrointestinal perforation:Treatmentusuallyinvolvessurgerytorepairtheperforation(hole).Sometimes,asmallpartoftheintestinemustberemoved.Atemporarycolostomy(asurgicalprocedurethatbringsoneendofthelargeintestineoutthroughtheabdominalwall,andallowsstoolsmovingthroughtheintestinedrainintoabagattachedtotheabdomen)orileostomy(asurgerytoremovepartorallofyoursmallintestinethatisblockedordiseased)maybeneeded.Antibioticsalonecanbeusedinrarecasestotreatpatientswhoseperforationshaveclosedontheirown.

H

Hand-and-foot syndrome:Applymoisturizertohandsandfeetliberallyandoften.Sitorlieonpaddedsurfacesofchairsormattresses.Raiselegswheneverpossiblewithcushions.Placeapillowbetweenkneesorwearpyjamas(preventsrubbinglegsduringsleep).Wearloose-fittingclothesandloose-fittingcomfortableshoes.Avoidthefollowing:Exposureofhandsandfeettoheatsuchashotwater;vigorousrubbingtopalmsandsoleswhenwashingorapplyingmoisturizers;activitiesthatcauserubbingofskinsurfaces;anyunnecessarywalking,joggingorvigorousexercise;andwalkingwithbarefeet.Toalleviatediscomforttrycoldpacksandothercoldontheaffectedareasprocedures(avoidcoldpacksifyouareonoxaliplatin-basedchemotherapyregimenasitmaymaketheneurotoxicitysymptomsworse),andover-the-counterpainmedication(e.g.acetaminophen).Tohelpsoothedry,irritatedskin,applyUdderlySmooth®UdderCreamorBagBalm® ointment2-3timesaday.

Headache:Over-the-countermedicationssuchasacetaminophen,ibuprofenoraspirinmaybeprescribedtotreatheadache.Ifyouhaveableedingdisorder,youshouldavoidaspirin.Alwaystalktoyourhealthcareprofessionalbeforetakinganymedications.

Hepatotoxicity:Treatment-relatedliverproblemsmightoccur.Youmayexperiencenausea,jaundice,swollenabdomen,painintheupperabdomen,ormentalconfusionasaresultofchemotherapy-inducedliverdamage.Thereisnotreatment forliverdamageonceitoccurs.Yourhealthcareprofessionalwilladviseyoutostoptakinganymedicationsthatareprocessedthroughtheliver,andmayprescribemedicationsthathelpreducethesymptomsofliverdamagesuchasadiuretictoreducefluidaccumulationorswellingbymakingyouurinateoutextrafluid.Ifyourliverisnotfunctioningproperlyavoidthefollowing:alcohol,acetaminophen,medicationsthathavecausedliverdysfunctioninthepast,andmedicationstotreathighbloodcholesterollevels,suchasatorvastatinorsimvastatin.Talktoyourhealthcareprofessionalbeforechanginganymedications.


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Managing Side Effects

Thissectionisdesignedtohelpyoumanagesideeffectswhichyoumayhaveinresponsetoyourtreatmentasdescribedunder“What are the possible side effects?”inthePersonalized Treatment Section ofthisguide.Foryourconvenience,sideeffectswiththetipsonhowtomanagethemarelistedinalphabeticalorderbelow.

A

Abdominal pain:Managementofabdominal painsdependsontheircauseandseverity,andcanbecontrolledwithover-the-countermedications.Changesindietinawaythathelpseithersloworspeedtheintestinalactivitycanhelpcontrol,andinsomecasespreventabdominalcramps.Dairy,soy,fatorwheatglutenproductsarenottoleratedwellbypatientsfollowingtreatmentforCRC.Yourhealthcareprofessionalcanassistyouinchoosingtherightover-the-countermedication,andmakingchangestoyourdiettohelpcontrolorpreventabdominal pain.

Allergic reaction:See“Hypersensitivity/Allergicreaction” .

Alopecia(hairloss):Usuallynewhairshouldregrowintheweeksormonthsaftertreatment.Insomecases,itmightnotregrow,whichismorecommonafterradiotherapythanafterchemotherapy.Tohelp youcopewiththehairlossconsiderthefollowing:Youmaywishtocutyourhairbeforeitstartsfalling outastheexperienceoflosingthehairissometimesworsethandealingwithitonceit’sgone;forwomen,planaheadandshopforawigbeforeyourhairisgone,especiallyifyouwishtomatchyournaturalcolor;wearinghatsorheadscarvesaregoodalternativesoracomplimenttoawig;avoidexposuretothesun,andcoveryourheadorusesunscreenonyourscalp.SkinthathasbeencoveredwithhairmaybeparticularlysensitivetoUVrays;askyourinsurancecompanyiftheycoverthecostofthewig;treatyournewhairgentlyonceitgrowsback,andavoidchemicals,bleach,peroxideorcolors.Considergettinginvolvedina“LookGood…FeelBetter”program,acommunity-based,free,nationalservicethatteachesfemalecancerpatientsbeautytechniquestohelprestoretheirappearanceandself-imageduringchemotherapyandradiationtreatments.Formoreinformationgotowww.lookgoodfeelbetter.org.

Anemia:Anemiaisthemostcommoncauseoftiredness,weaknessorfatigue.Tohelpdealwiththesesymptomsgetplentyofrestbytakingnapsduringtheday,andgotobedearlierthanusual;Eatawell-balanceddiet,andasktospeaktoanutritionist,whowillhelpyouchoosegood,strengtheningfoodsthatappealtoyou;trytostayactiveandtakeshortwalksaslightexercisemayhelp;restrictunnecessaryactivities,saveyourenergybydoingthethingsthatarereallyimportant,andletothershelpyoubytakingoversomechoresandtasks.

Arterial thromboembolism:See“Thromboembolism”.

D

Dehydration(lackofappropriateamountoffluidinthebody):Cancerpatientsmusthaveadequatefluidtoremovetoxinsfromthebodyaswellasproteinsreleasedbydyingcells.Takeinasmuchfluidonaspossibleonadailybasis,butdonotdrinkproductscontainingelectrolytes(suchassportsdrinks)unlessinstructedtodosobyyourhealthcareprofessional.Incasesofseveredehydration,hydrationtherapy throughIVisusuallyadministeredinthehospitalsetting.

54

The words in the

Managing Side

Effects section

marked in italics

can be found

in the Glossary.

Neurotoxicity/neuropathy:Duringinfusion,wearablankettokeepwarm;Avoidactivitiesthatrequireyoutogooutdoorsduringcoldweather,andifyougoout,makesureyoudresswarmly;Coveryourskinbeforeyouentercoldplaces;Don’ttouchcoldsurfacesorobjects,orwashyourhandswithcoldwater;Avoidbreathingindeeplywhenexposedtocoldairoutsideortoairconditioners;Donotuseicetosoothemouthsoresoreasenausea;andAvoideatingfrozenorcoldfoods,anddrinkingcoldbeveragesorusingice.

Neutropenia(lowwhitebloodcellcount):Rarely,cancerpatientsmayexperienceneutropenia,whichincludesinfectionsandfever/febrile neutropenia,fromchemotherapyorasaresultoftheirunderlyingcancer.Dependingonthecauseofneutropenia,yourhealthcareprofessionalwilldeterminethetreatmentthatisrightforyou.Ifthefeverisdeterminedtoberelatedtoaninfection,treatmentwillbeprescribedfortheinfection.Forabacterialinfection,antibioticsareusuallyprescribed;forviralinfections,theusualtreatmentisoftenrestandplentyoffluids,althoughantiviraldrugsmaybeusedtotreatsomeviruses.Ifaninfection-relatedfeverisveryhigh,over-the-countermedicationssuchasacetaminophen,ibuprofenmaybeprescribedtoreducethefeverandassociateddiscomfort.Ifyouhaveableedingdisorder,youshouldavoidthesemedications.Alwaystalktoyourhealthcareprofessionalbeforetakinganymedications.Whileitmaybedifficulttopreventfeversresultingfrominfectionsduetoneutropenia,somemeasurestohelppreventinfectionsmayinclude:avoidingscratchesandcutsviagentlehandlingoftheskin;frequenthand-washing;pattingskindryratherthanrubbing;thoroughcookingoffood;reducinghumancontactsoastoreducethepotentialofcontractinganinfection:andavoidinggardeningandhandlingpetlitters.

P

Pain(joint,muscle,bone,chest/thorax,abdomen,head/headache,orrectum):Medicationscanbeusedforpainrelief,andareusuallyselectedaccordingtotheneedsofthepatient.Forsomekindsofpainrelatedtocancer,non-prescriptionover-the-countermedicationssuchasacetaminophen,ibuprofen,maybesufficient.Forotherdegreesandkindsofpain,prescriptionmedicationsareused.Yourhealthcareprofessionalwilldeterminewhichtypeofmedicationisappropriateforyourtypeofpain .

Pulmonary embolism:“Thromboembolism”.

S

Skin rash:See“Hypersensitivity/allergicreaction”.

Skin reactions(rash,acne,itching,nailchanges,andinfusion-relatedreactions):See“Skinreaction/acne”.

Skin reaction/acne:Forskinreactions,uselotionsthatdonotcontainalcoholtocooltheskin.Ifyourrashisaresultofanallergic reactiontoadrug,yourhealthcareprofessionalmaystopthedrug.Forminor,non-allergicskinreactions,yourhealthcareprofessionalmayrecommendoneofthefollowing:corticosteroidcreamtoreducehelpinflammation;antihistaminetohelpreducesymptomsofanallergic reaction,suchasrash,hivesandshortnessofbreath;analgesics,over-the-countermedicationssuchasacetaminophenoraspirin,tohelprelievepainassociatedwitharash.Tohelpmanagearash:Wearloose,non-bindingclothing;usemildsoapwithoutperfumes;dryyourskincarefullyafterbathing;avoidharshchemicals;protectyourskinfromthesunwithsunscreensorlong,looseclothing;trynottoscratch,andtalktoyourhealthcareprofessionalaboutanti-acnemedications.

Stomatitis/mucositis:Forthetreatmentofstomatitis(mouthsores):Practicegoodoralcarebyfrequentlyrinsingthemouthwithsaline/saltwaterandbrushingteeth2-3timesperday;mouthwashes(saltandsodamouthwashcanhelprelievemouthsoresaswellasmedicatedmouthwashes;suckonicechipstominimizethedamagefromchemotherapydrugs(avoidcoldpacksifyouareonoxaliplatin-basedchemotherapyregimenasitmaymaketheneurotoxicitysymptomsworse);avoidveryhotfoods,carbonatedbeverages,andeatsoftfoodsuntilthesoresheal.Forthetreatmentofmucositis(inflammationofthemucosa)whetherinthemouth,pharynx,esophagus,trachea,bowel,bladderorrectum:Avoidingirritationbykeepingfoodorstoolssoftandpreventingtraumaofanykind;uselocalanalgesic(pain-killing)mixtures,antibioticsorsteroids;keephydratedbytakinginfluids;andeatfoodslowinfibreifyouhavebowelreaction.


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Hypersensitivity/allergic reaction:Medicationssuchasantihistamines,epinephrineandsteroidscanbeusedtotreatallergic reactions.Severereactionsmayrequireothertherapy,suchascorticosteroids,oxygentherapy,narcotics,orpulmonaryrehabilitationforbreathingdifficulties/shortnessofbreathorintravenous fluidstoboostbloodpressureinanaphylacticshock.Tohelpmanagebreathingdifficulties,therearethingsyoucandoeverydaysuchas:relaxationtechniquestocontrolyourbreathing(meditation,yoga,ordeepbreathingexercises);promoteoxygenation(aircirculation)throughoutyourlungstohelppreventinfection andpneumoniawithbreathingexercisesorphysicalactivity;useaspirometer,adevicethatmakesyoubreatheslowlyanddeeply,tomaintainoxygenation;findakindofexercisethatyoucantolerateanddoitdaily;avoidsmokingandsmoke-filledenvironments;andreduceanxietyandmanagestress.

Itisdifficulttopredictwhichpatientswilldevelopanallergic reactiontotheirCRC therapies,whichmakesitdifficulttoprevent.Ifyoudevelopatreatment-relatedallergic reaction,talktoyourhealthcareprofessionalaboutavailableremediesthatarerightforyou.

Hypertension(highbloodpressure):HighbloodpressurecandeveloptemporarilyasaresultoftreatmentforCRC.Youmayexperiencerapidpulse,fluidretention,headache,orothersymptomsofhighbloodpressure.Tohelplowerbloodpressure,engageinregularaerobicexercise,weightreduction(ifoverweight)andsaltrestriction.Ifyourbloodpressureisstillhighafteryoutriedtheseoptions,yourhealthcareprofessionalmayprescribeantihypertensivemedicationsdesignedtolowerbloodpressure.

I

Infection:See“Neutropenia”.

Infusion reactions:See“Hypersensitivity/”.

M

Mucositis:See“Stomatitis/mucositis”.

N

Nausea/vomiting:Thefollowingtipscanhelpyoumanagenauseaandvomiting.Eating tips:Ifyourtreatmentcausesnausea,donoteatforatleast1or2hoursbeforetreatment,oreatalightmealbeforeyourtreatment;eatwhatappealstoyou,anddon’tforceyourselftoeatunappealingfoods;inplaceoflargermeals,eatmorefrequentandsmallermealsandsnacksbeforehungersetsinsincefeelingsofhungercanmakeyournauseaworse;avoidfoodsthathaveastrongodour,arehighinfat,orarefried,spicy,orverysweet;restaftereating,sittingupratherthanlyingdown;andifyouhavemorningnausea,tryeatingdryfoodslikecereal,toast,orcrackers,unlessyouhavesoresinyourthroatormouth,orverylittlesaliva.Drinking tips:Limitdrinksthatleaveyoufeelingbloated;drinkslowly,withastrawifithelpsyoutodrinkmoreslowly;drinkroom-temperatureliquidsfrequently,andinsmallamounts;anddrinkcool(notcold(re:mayexacerbateneuropathy),clear,unsweetenedjuicesorflat,light-colouredsoftdrinkswithoutcaffeine.

Foodsthatareeasyonyourstomachincludecannedfruit,cookedcereal,rice,noodles,potatoes,clearliquids(sportsdrinks,clearsoftdrinkssuchasgingerale),tea,broth,andwater.

Ifyouarevomiting,avoideatingordrinkinguntilit’sundercontrol,thentrysmallamountsofclearliquidsandworkuptoafullliquiddietorasoftdiet.Ifyouhavenauseaandvomitingthatissevereorlastsmorethanaday,oryoucan’tkeepliquidsdown,contactyourhealthcareprofessional,andheorshemaysuggestantinauseamedicationorothertreatment.

Formoredietarytips,askyourhealthcareprofessionaltoreferyoutoadietician.

56

Colorectal Cancer Glossary4,25,26,49

5-fluorouracil (5-FU):Adrugusedasatreatmentusuallyforcolorectal cancer.Itisatypeofanti-metabolite(adrugthatisverysimilartonaturalchemicalsinanormalcellularreactionsbutdifferentenoughtointerferewithcelldivisionandfunction).AlsoseeFluorouracil .

5-FU:See5-fluorouracil .

A

Abdomen:Theareaofthebodythatcontainsthepancreas,stomach,intestines,liver,gallbladder,andotherorgans.

Abdominal:Havingtodowiththeabdomen,whichisthepartofthebodybetweenthechestandthehipsthatcontains thepancreas,stomach,intestines,liver,gallbladder,andotherorgans.

Abscess:Anenclosedcollectionofpusintissues,organs,orconfinedspacesinthebody.Anabscessisasignofinfection andisusuallyswollenandinflamed.

Adjuvant therapy:Treatmentgivenaftertheprimary(main)treatmentisreceived,andallvisiblesignsofthecancer removed,tohelpincreasethechancesofacure.Adjuvant therapymayincludechemotherapy,radiation therapyorothertherapy.AlsoseeNeoadjuvant therapy .

Alopecia:Thelackorlossofhairfromareasofthebodywherehairisusuallyfound.Alopeciacanbeasideeffectofsomecancertreatments.

Anemia:Aconditioninwhichthenumberofredbloodcellsisbelownormal,resultinginareductionintheamountofoxygenthatcanbecarriedtothevariousbodypartsandtissues,causingfatigueortiredness,weakness,troublebreathing,rapidheartbeat,dizziness,lightheadedness,inabilitytoconcentrate,orheadache.

Antibody:Aproteinmadebyplasmacells(atypeofwhitebloodcell)inresponsetoanantigen(asubstancethatcausesthebodytomakeaspecificimmuneresponse).Eachantibodycanbindtoonlyonespecificantigen.Thepurposeofthisbindingistohelpdestroytheantigen.Someantibodiesdestroyantigensdirectly.Othersmakeiteasierforwhitebloodcellstodestroytheantigen.AlsoseeMonoclonal antibody .

Arterial thromboembolism:Theblockingofanarterybyaclotofforeignmaterial.Thiscanbedoneastreatmenttoblocktheflowofbloodtoatumour.Alsocalledembolization.

B

Bevacizumab:Itisnotchemotherapybutisgivenincombinationwithaspecifictypeofchemotherapy.Whilechemotherapyattacksthetumourdirectly,bevacizumabwhichisamonoclonal antibodyattacksthebloodvesselsthatsurroundthetumour.Inordertogrowandspread,tumoursneedaconstantsupplyofoxygenandothernutrients.Tumours getthissupplybycreatingtheirownnetworkofbloodvessels.Thisprocessiscalledangiogenesis,andbevacizumabworksbyblockingangiogenesis.Bypreventingthegrowthofnewbloodvessels,bevacizumabhelpsstarvethetumourofoxygenandothernutrients.Thismakesithardforthetumourtogrow.

BEV:seeBevacizumab .

Biomarker:Alsocalledmolecularmarker,isabiologicalmoleculefoundinblood,otherbodyfluids,ortissuesthatisasignofanormalorabnormalprocess,orofaconditionordisease.Abiomarkermaybeusedtoseehowwellthebodyrespondstoatreatmentforadiseaseorcondition.Alsocalledmolecularmarker.

Biomarker Testing:Atestofblood,orotherbodyfluidortissuesdonetolookforabiomarkerofaconditionordisease. Abiomarkermaybeusedtoseehowwellthebodyrespondstoatreatmentforadiseaseorcondition.


59

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ary

T

Thrombocytopenia(lowplateletcount):Plateletsarethecellsthatformbloodclotsthatstopbleeding.Lowplateletcountcancausebleeding.Checkwithyourhealthcareprofessionalbeforetakinganykindofmedication,vitamin,orpill.SomemedicationslikeASA(Aspirin)canaffectbloodclotting,andcontributetobleeding.Tohelppreventbleeding:Useaverysofttoothbrushorcottonswab;blowyournosegently,anduseaverysofttissue;trynottocutornickyourselfwithanysharpitems,andifyoushave,switchtoanelectricrazor;andavoidactivitiesthatcouldcauseaninjury,likecontactsports.

Thromboembolism(orembolism):IfyouareatriskforbloodclotformationasaresultofyourCRC treatment,yourhealthcareprofessionalwillprescribeanticoagulantdrugsuchaswarfarinorheparintohelppreventbloodclots.

For more information on description/symptoms, cause, remedy/treatment, and prevention of side effects, and ways to manage them, visit Colorectal Cancer Association of Canada website at www.colorectal-cancer.ca/en/treatments/addressing-effects/.1

Talk to your healthcare professional if you have additional questions or need more information on your possible side effects and how to manage them.

58

D

Dehydration:Aconditioncausedbythelossoftoomuchwaterfromthebody.Severediarrheaorvomitingcancausedehydration .

Differentiation(differentiated):Incancer,referstohowmature(developedordifferentiated)thecancercellsareinatumour.Differentiatedtumourcellsresemblenormalcellsandtendtogrowandspreadataslowerratethanundifferentiatedorpoorlydifferentiatedtumourcells,whichlackthestructureandfunctionofnormalcellsandgrowuncontrollably.

DNA:Themoleculesinsidecellsthatcarrygeneticinformationandpassitfromonegenerationtothenext.Alsocalleddeoxyribonucleicacid.

E

EGFR:Theproteinfoundonthesurfaceofsomecellsandtowhichepidermalgrowthfactorbinds,causingthecellstodivide.Itisfoundatabnormallyhighlevelsonthesurfaceofmanytypesofcancercells,sothesecellsmaydivideexcessivelyinthepresenceofepidermalgrowthfactor.Alsocalledepidermal growth factor receptor,ErbB1,andHER1.

Embolism:Ablockinanarterycausedbybloodclotsorothersubstances,suchasfatglobules,infectedtissue,or cancercells.

Epidermal growth factor receptor:seeEGFR

External beam radiation therapy:Amachinelocatedoutsidethebodyisusedtodirectradiationatthecancerandsurroundingtissue.Thistypeofradiationisusedtotreatmosttypesofcancer,anditisdoneonanoutpatientbasis.PatientstypicallyreceiveonetreatmenteverydayfromMondaythroughFridayandacourseoftreatmentmaycontinueforseveralweeks.

F

Febrile neutropenia:Aconditionmarkedbyfeverandalower-than-normalnumberofneutrophilsintheblood.Aneutrophilisatypeofwhitebloodcellthathelpsfightinfection.Havingtoofewneutrophilsincreasestheriskofinfection . AlsoseeNeutropenia .

Fluoropyrimidine:Oneofagroupofsubstancesusedtotreatcancer.Afluoropyrimidineisatypeofantimetaboliteincludingdrugssuchascapecitabineandfluorouracil(5-FU).

Fluorouracil:Anticancerdrugusedtotreatsymptomsofcancerofthecolon,breast,stomach,andpancreas.Itisalsousedinacreamtotreatcertainskinconditions.FluorouracilstopscellsfrommakingDNAanditmaykillcancercells.Itisatypeofantimetabolitewhichinterfereswithcellgrowth.Alsocalled5-fluorouraciland5-FU .

G

Gastrointestinal:Referstothestomachandintestines.AlsocalledGI.

Gastrointestinal perforation:Aholethatdevelopsthroughtheentirewallofthestomach,smallintestine,largebowel, orgallbladder.

Gene:Thefunctionalandphysicalunitofhereditypassedfromparenttooffspring.GenesarepiecesofDNA,andmostgenescontaintheinformationformakingaspecificprotein .

H

Hand-and-foot syndrome:Aconditionmarkedbypain,swelling,numbness,tingling,orrednessofthehandsorfeet. Itsometimesoccursasasideeffectofcertainanticancerdrugs.Alsocalledpalmar-plantarerythrodysesthesia.


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Biopsy:Aprocedureinwhichasampleofcanceroustissueisremovedforanalysisunderthemicroscopetohelppreciselydiagnosethetypeofcanceranditsgrade.

Bolus:Asingledoseofadrugorothersubstancegivenoverashortperiodoftime.Itisusuallygivenbyinfusionorinjectionintoabloodvessel.Itmayalsobegivenbymouth.

Brachytherapy:Atypeofcontactradiation therapythatusesasealedradioactivesource(animplant),whichisplacedinornearthetumour,andmakesitpossibletotreatcancerwithhighradiationdosesinaveryfocusedmanner.

BRAF gene:AgenethatmakesaproteincalledB-RAF,whichisinvolvedinsendingsignalsincellsandincellgrowth.Thisgenemaybemutated(changed)inmanytypesofcancer,whichcausesachangeintheB-RAFprotein.Thiscanincreasethegrowthandspreadofcancercells.

BRAF Mutation:AmutationintheBRAF genethatmakespatientswithcolorectal cancernon-responsivetotreatmentswithcetuximabandpanitumumab .

C

Cancer:Atermtodescribediseasesinwhichabnormalcellsdivideuncontrollablyandcaninvadenearbytissues.Alsocalledmalignancy.

Capecitabine:Belongstoafamilyofmedicationscalledthefluoropyrimidines(medicationsthatinterferewiththegrowthofcellsthatrapidlydivideinthebody,includingcancercells).Capecitabineisaninactivesubstanceonitsown.Whencapecitabineistaken,itischangedinthebody,mostlywithinthetumour (cancercells),tobecomethecommonlyusedcancermedicationcalled5-fluorouracil(alsoknownas5-FU).Insomepatients5-FUwillkillcancercellsanddecreasethesizeofthetumour .

Carcinoma in situ:Alsocalledstage0cancer,itisagroupofabnormalcellsthatareconfinedtotheplaceinthebodywheretheyfirstformed,anddonotspread.Theseabnormalcellsmaybecomecancerousandspreadintonearbynormaltissue.Inthebowel,in-situcarcinomaistypicallyseenonthesurfaceof apolyp .

Cell:Theindividualunitthatmakesupthetissuesofthebody.Alllivingthingsaremadeupofoneormorecells.

Cetuximab:Amonoclonal antibodythatrecognizesandattachestocolorectal cancercellsthatexpressepidermal growth factor receptor (EGFR)withnon-mutated(wild-type)KRASafterfailureofchemotherapy regimenscontainingfluoropyrimidine,oxaliplatin,andirinotecan,andpreventsthecancercellsfromgrowinganddividing.

Chemoradiation:Treatmentthatcombineschemotherapywithradiation therapy.Alsocalledchemoradiotherapy.

Chemotherapy:Drugtreatmentsthathelpdestroycancercellsbyinterferingwiththecancercellsabilitytodivide.Thesedrugtreatmentsaretypicallygiveneveryfewweekstherebyallowingnormaltissuesandbloodcountstorecoverintheinterval.

Clinical Trial:Aresearchstudydesignedtoansweraquestionabouttheeffectivenessofnewtherapiesornewwaysofusingalreadyexistingtherapies,anddeterminewhethertheyaresafeandeffective.

Colorectal:Havingtodowiththecolonortherectum.

Colorectal cancer:Cancerthatdevelopsinthecolon(thelongestpartofthelargeintestine)and/ortherectum(thelastseveralinchesofthelargeintestinebeforetheanus).AlsoreferredtoasCRC .

CRC:SeeColorectal cancer .

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Locally advanced cancer:Adescriptivetermtodescribecancerthathasspreadfromwhereitstartedontheinnersurfaceofthebowel,throughthebowelwalltoinvolvenearbytissuesorlymph nodes .

LV:SeeLeucovorin .

Lymph node:Alsocalledlymphgland,isaroundedmassoflymphatictissue.Lymph nodesfilterlymph(lymphaticfluid)andcantrapforawhilecancercellsthatareleavinganorgan.Inthebowel,lymph nodesarepresentonthesurfaceofthebowelandalongthebloodvesselsgoingtothebowel.Removingthemisanimportantaspectoftheinitialsurgery.Whenthemaligs areinvolvedincolorectal(bowel)cancers,theStageautomaticallybecomes3(or4ifdistantorgansarealsoinvolved).

M

Malignant:Cancerous.Malignantcellscaninvadeanddestroynearbytissueandspreadtootherpartsofthebody.

Metastasis(ormetastases):Thespreadofcancerfromonepartofthebodytoanother.Atumourformedbycancerouscellsthathavespreadfromitsoriginallocationiscalleda“metastatictumour”ora“metastasis”orthepluralform,“metastases”,ifthereismorethanone.Themetastatictumourcontainscellsthatarelikethosewhichcamefromtheoriginal(primary)tumour .

Metastatic:Acancerthathasspreadfromwhereitstarted(primarytumour)toother(distant)partsofthebodysuchas theliverandlungs.

Mitomycin C:AnticancerdrugthatdamagesDNA,preventingcelldivision,whichleadstocancer celldeath.

Monoclonal antibody:Asubstancesuchasproteinwhichismadeinthelaboratory.Theseantibodiesaredesignedtohaveanexactattractionforcertainmoleculesfoundonthesurfaceofcells,includingcancercells.Therearemanykindsofmonoclonalantibodies.Eachmonoclonal antibodyismadetofindonesubstance.Monoclonalantibodiesaredesignedtotargetthemalignant(cancerous)cellsthatformthetumour,andareusedtotreatsometypesofcancer.AlsoseeTargeted therapy .

Mucosa:Alsocalledmucous membraneisthemoist,innerliningofsomeorgansandbodycavitiessuchasthenose,mouth,lungs,andstomach.Glandsinthemucosamakemucus(athick,slipperyfluid).

Mucositis:Acomplicationofsomecancertherapiesinwhichtheliningofthedigestivesystembecomesinflamed.Oftenseenassoresinthemouthorstomatitis .

Mucous membrane:Themoist,innerliningofsomeorgansandbodycavities(suchasthenose,mouth,lungs,andstomach).Glandsinthemucous membranemakemucus(athick,slipperyfluid).Alsocalledmucosa .

Mutation:AnychangeintheDNAofacell . Mutationsmaybecausedbymistakesduringcelldivision,ortheymaybecausedbyexposuretoDNA-damagingagentsintheenvironment.Mutationscanbeharmful,beneficial,orhavenoeffect.Iftheyoccurincellsthatmakeeggsorsperm,theycanbeinherited;ifmutationsoccurinothertypesofcells,theyarenotinherited.Certainmutationsmayleadtocancerorotherdiseases.

N

Neoadjuvant therapy:Treatmentgivenbeforetheprimarysurgicaltreatment.Examplesofneoadjuvant therapyincludechemotherapy, radiation therapy, or other therapies. Neoadjuvant therapyisusuallygiventomakethesurgeryeasierandmoreeffective.AlsoseeAdjuvant therapy .

Neurological or neurologic:Havingtodowithnervesorthenervoussystem.

Neuropathy:Anerveproblemthatcausespain,numbness,tingling,swelling,ormuscleweaknessindifferentpartsofthebody.Itusuallybeginsinthehandsorfeetandgetsworseovertime.Neuropathymaybecausedbyphysicalinjury,infection,toxicsubstances,disease(suchascancer,diabetes,kidneyfailure,ormalnutrition),ordrugs,includinganticancerdrugs.Alsocalledperipheralneuropathy.


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Hepatotoxicity:Poisonousorharmfultotheliver.Hepaticreferstotheliver,andtoxicityistheextenttowhichsomethingispoisonousorharmful.

HiPEC:SeeHyperthermic Intraperitoneal Chemotherapy .

Hypersensitivity:Anexaggeratedresponsebytheimmune systemtoadrugorothersubstance.Alsocalledanallergic reaction .

Hypertension:Abloodpressureof140/90orhigher.Hypertensionusuallyhasnosymptoms.Itcanharmthearteriesandcauseanincreaseintheriskofstroke,heartattack,kidneyfailure,andblindness.Alsocalledhighbloodpressure.

Hyperthermic Intraperitoneal Chemotherapy(orHiPEC):isusedforcancersthatareconfinedtotheperitoneal(abdominal)cavityandareotherwisedifficulttotreatwithotheravailabletreatments.HiPECisatreatmentoptionforpatientswhosecancersaredifficulttotreatsuchasthosethatspreadtotheliningsurfacesoftheperitoneal(abdominal)cavityfromprimary colorectal cancer.“Intraperitoneal”meansthatthetreatmentisdeliveredtotheabdominalcavity,andterm“HyperthermicChemotherapy”meansthatthesolutioncontainingchemotherapy(anticancerdrugs)isheatedtoatemperaturethatishigherthannormalbodytemperature.

I

Immune system:Thecomplexgroupoforgansandcellsthatdefendsthebodyagainstinfectionsandotherdiseases.

Inflammation:Redness,swelling,pain,and/orafeelingofheatinanareaofthebody.Thisisaprotectivereactiontoinjury,disease,orirritationofthetissues.

Infusion:Amethodofinjectingfluids,includingdrugs,intothebloodstream.Alsocalledintravenous infusion .

Intra-abdominal:Insidetheabdomen(theareaofthebodythatcontainsthepancreas,stomach,intestines,liver,gallbladder,andotherorgans).

Intravenous:Givingchemotherapydrugintoavein.AlsocalledintravenouslyorIV.

Irinotecan:Anticancerdrugthatworksbykillingrapidlydividingcells,suchascancercells.

IV:seeIntravenous .

K

KRAS gene:Agenethatmaycausecancerwhenitismutated(changed).TheKRAS genemakestheKRASprotein,whichisinvolvedincellsignalingpathways,cellgrowth,andapoptosis(celldeath).AgentsthatblocktheactivityofthemutatedKRAS geneoritsproteinmaystopthegrowthofcancer.AlsocalledK-rasgene .

KRAS mutation:achange(ormutation)intheKRAS gene,whichwhenmutatedcanleadtocancer.Amutationinthisgenemakespatientswithcolorectal cancernon-responsivetotreatmentswithcetuximab andpanitumumab.AlsoseeGene and KRAS gene .

L

Leucovorin:Giventogetherwithanticancerdrugssuchasfluorouracil,tohelplessenthetoxiceffectsofthesemedications,thus“rescuing”thepatientwhilepermittingtheanticanceractivityofthedrugslikeFU.Italsoenhancestheeffectsoffluorouracilanditsderivativesbystabilizingthebindingofthedrug’smetabolitetoitstargetenzyme,thusprolongingdrugactivity.AlsocalledLVorfolinicacid.

Liver metastasis:Cancerthathasspreadfromtheoriginal(primary)tumourtotheliver.

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Radiochemotherapy:Cancertreatment,inwhichchemotherapy (5-FU or capecitabine)combinedwithradiation therapy,isusedbeforesurgerytoimprovethechancesofbettertumourcontrolandreducelocalrecurrences(cancerfromcomingback).

Recurrence:Cancerthathasrecurred(comeback),usuallyafteraperiodoftimeduringwhichthecancercouldnotbedetected.Thecancermaycomebacktothesameplaceastheoriginal(primary)tumourortoanotherplaceinthebody. Alsocalledrecurrent cancer .

Recurrent cancer:SeeRecurrence .

Resistant cancer:Cancerthatdoesnotrespondtotreatment.Thecancermayberesistantatthebeginningoftreatment,oritmaybecomeresistantduringtreatment.Alsocalledrefractorycancer .

S

Stomatitis:Inflammation(redness,swelling,pain,and/orafeelingofheat)orirritationofthemucous membranesinthemouth.Mucous membrane,alsocalledmucosa,isthemoist,innerliningofthemouth.

T

Targeted therapy:Atypeoftreatmentthatusesdrugsorothersubstances,suchasmonoclonalantibodies,tofindandattackspecificcancercells.Targeted therapymayhavefewersideeffectsthanothertypesofcancertreatments.

Therapy:AnotherwordforTreatment.

Thrombocytopenia:Aconditioninwhichthereisalower-than-normalnumberofplateletsintheblood.Itmayresultineasybruisingandexcessivebleedingfromwoundsorbleedinginmucous membranesandothertissues.

Thromboembolism:Formationinabloodvesselofaclot(thrombus)thatbreakslooseandiscarriedbythebloodstreamtopluganothervessel.Theclotmayplugavesselinthelungs(pulmonary embolism),brain(stroke),gastrointestinaltract,kidneys,orleg.Thromboembolismisanimportantcauseofmorbidity(disease)andmortality(death),especiallyinadults.Treatmentmayinvolveanticoagulants(bloodthinners),aspirin,orvasodilators(drugsthatrelaxandwidenvessels).

Toxicity:Theextenttowhichsomethingispoisonousorharmful.

Toxin:Apoisonmadebycertainbacteria,plants,oranimals,includinginsects.

Tumour:Anabnormalmassoftissuethatresultswhencellsdividemorethantheyshouldordonotdiewhentheyshould.Tumoursmaybebenign(notcancer),ormalignant(cancer).Alsocalledneoplasm.

V

Vascular endothelial growth factor:AlsocalledVEGF,isamoleculethathelpsnewbloodvesselstoform.ThereceptoristhepartofthecellthatreceivestheVEGFsignal.IdentifyingthesepolymorphismsmayhelpdoctorstodecidetousetargetedtherapiesagainstVEGFforthissubgroupofpeoplewithcoloncancer

VEGF:Seevascular endothelial growth factor .

W

Wound:Abreakintheskinorotherbodytissuescausedbyinjuryorsurgicalincision(cut).


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Neurotoxicity:Thetendencyofsometreatmentstocausedamagetothenervoussystem.

Neutropenia:Aconditioninwhichthereisalower-than-normalnumberofneutrophils(atypeofwhitebloodcell).SeeFebrile Neutropenia .

O

Oxaliplatin:AnticancerdrugwhichattachestotheDNA(geneticmaterialcontainedinthecell)andinterfereswithcelldivision,causingtheeventualdeathofthecancer cell .

P

Palliative care:Aspecializedareaofhealthcarethatfocusesonrelievingandpreventingthesufferingofpatients,andisgiventoimprovethequalityoflifeofpatientswhohaveaseriousorlife-threateningdisease.Thegoalofpalliative careistopreventortreatasearlyaspossiblethesymptomsofadisease,sideeffectscausedbytreatmentofadisease,andpsychological,social,andspiritualproblemsrelatedtoadiseaseoritstreatment.Alsocalledcomfortcare,supportivecare,andsymptommanagement.Unlikehospicecare,palliativemedicineisappropriateforpatientsinalldiseasestages,includingthoseundergoingtreatmentforcurableillnessesandthoselivingwithchronicdiseases,aswellaspatientswhoarenearingtheendoflife.

Panitumumab:Amonoclonal antibodythatrecognizesandattachestocolorectal cancercellsthatexpressepidermal growth factor receptor (EGFR)withnon-mutated(wild-type)KRASafterfailureofchemotherapy regimenscontainingfluoropyrimidine,oxaliplatin,andirinotecan,andpreventsthecancercellsfromgrowinganddividing.

Partial liver resection for colorectal liver metastasis:Surgerytoremovetissueorpartofanorgan, inthiscasealiver,towhichcancerhasspread.

Polyp:Agrowththatprotrudesfromamucous membrane,whichisthemoistinnerliningofcavitiessuchasthenose,mouth,stomachandbowel.

Primary colorectal cancer:Heretheword“primary”describeswherethecanceroriginated.Inthiscaseacancerstartinginthebowel(specificallythecolonorrectum).

Protein:Amoleculemadeupofaminoacidsthatareneededforthebodytofunctionproperly.Proteinsarethebasisofbodystructuressuchasskinandhairandofsubstancessuchasenzymes,cytokines,andantibodies.

Proteinuria:Higher-than-normalamountofproteinintheblood.

Pseudo-adjuvant chemotherapy:Beyondpartial liver resection,therationaleforpseudo-adjuvant chemotherapylacksscientificevidence,despitesomepromisingdata.

Pulmonary:Havingtodowiththelungs.

Pulmonary embolism:Ablockinanarteryofthelungcausedbybloodclotsorothersubstances,suchasfatglobules,infectedtissue,orcancercells.

R

Radiation therapy(alsocalledradiotherapy):Theuseofhigh-energyradiationfromx-rays,gammarays,neutrons,protons,andothersourcestokillcancercellsandshrinktumours.AlsoseeExternal beam radiation therapyandbrachytherapy .

Radioactive:Asubstancethatgivesoffradiation.

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14.BujkoK,MowackiMP,Nasierowska-GuttmejerA,MichalskiW,BebenekM,KryjM;PolishColorectalStudyGroup.Long-termresultsofarandomizedtrialcomparingpreoperativeshortcourseradiotherapywithpreoperativeconventionallyfractionatedchemoradiationforrectalcancer.BrJSurg2006;93:1215-23.

15.UpToDate.Patientinformation:Colorectalcancertreatment;metastaticcancer.Availableat:www.uptodate.com/contents/patient-information-colorectal-cancer-treatment-metastatic-cancer.AccessedOctober6,2011.

16.AdamR,DelvartV,PascalG,etal.Rescuesurgeryforunresectablecolorectallivermetastasesdownstagedbychemotherapy:amodeltopredictlong-termsurvival.AnnSurg.2004;240:644.

17.Avastin®(bevacizumab)ProductMonograph.Hoffmann-LaRocheLimited.January28,2008.18.SouglakosJ,AndroulakisN,SyrigosK,etal.FOLFOX(folinicacid,5-fluorouracil,oxaliplatinandirinotecan)vsFOLFIRI

(folinicacid,5-fluorouracilandirinotecan)asfirst-linetreatmentinmetastaticcolorectalcancer(MCC):amulticentrerandomisedphaseIIItrialfromtheHellenicOncologyResearchGroup(HORG).Br.J.Cancer.2006;94(6):798-805

19.Erbitux®(cetuximab)ProductMonograph.Bristol-MyersSquibbCanada.May25,2010.20.Vectibix®(panitumumab)ProductMonograph.AmgenManufacturing,Limited,asubsidiaryofAmgenInc.

December22,2010.21.CancerCare.Availableat:www.cancercare.org/pdf/fact_sheets/fs_col_KRAS.pdf.AccessedOctober6,2011.22.NationalComprehensiveCancernetwork(NCCN)Guidelines.RectalCancer.Version3.2011.Availableat:

nccn.org.AccessedJuly4,2011.23.NationalComprehensiveCancernetwork(NCCN)Guidelines.ColonCancer.Version4.2011.Availableat:

nccn.org.AccessedJuly4,2011.24.HiPECTreatment.Availableat:www.hipectreatment.com/documents/hipec.php.AccessedOctober6,2011.25.NCIDrugDictionary.NationalCancerInstituteattheNationalInstitutesofHealth.Availableat:

www.cancer.gov/drugdictionary.AccessedJuly4,2011.26.DictionaryofCancerTerms.NationalCancerInstituteattheNationalInstitutesofHealth.Availableat:

www.cancer.gov/dictionary.AccessedJuly4,2011.27.AndréT,BoniC,NavarroM,etal.Improvedoverallsurvivalwithoxaliplatin,fluorouracil,andleucovorinasadjuvant

treatmentinstageIIorIIIcoloncancerintheMOSAICtrial.JClinOncol.2009Jul1;27(19):3109-16.28.Eloxatin®(oxaliplatinforinjection)ProductMonograph.sanofi-aventisCanadaInc.September17,2010.29.WolmarkN,YothersG,O’ConnellMJ,etal.AphaseIIItrialcomparingmFOLFOX6tomFOLFOX6plusbevacizumabin

stageIIorIIIcarcinomaofthecolon:ResultsofNSABPProtocolC-08.JClinOncol.27:18s,2009(suppl;abstrLBA4).30.AllegraCJ,YothersG,MichaelJ.O’ConnellMJ,etal.InitialSafetyReportofNSABPC-08:ARandomizedPhaseIII

StudyofModifiedFOLFOX6WithorWithoutBevacizumabfortheAdjuvantTreatmentofPatientsWithStageIIorIIIColonCancer.JClinOncol.2009;27(20):3385-3390.

31.TournigandC,AndréT,AchilleE,etal.FOLFIRIfollowedbyFOLFOX6orthereversesequenceinadvancedcolorectalcancer:arandomizedGERCORstudy.JClinOncol.2004;15;22(2):229-37.

32.CassidyJ,SClarkeS,EDíaz-RubioE,etal.XELOXvsFOLFOX-4asfirst-linetherapyformetastaticcolorectalcancer:NO16966updatedresults.BrJCancer2011;1-7.(doi:10.1038/bjc.2011.201)]

33.DeGramontA,FigerA,SeymourM,etal.Leucovorinandfluorouracilwithorwithoutoxaliplatinasfirst-linetreatmentinadvancedcolorectalcancer.JClinOncol2000;18:2938–2947.

34.BokemeyerC,BondarenkoI,MakhsonA,etal.Fluorouracil,leucovorin,andoxaliplatinwithandwithoutcetuximabinthefirst-linetreatmentofmetastaticcolorectalcancer.JClinOncol.2009;10;27(5):663-71.

35.GrotheyA,SugrueMM,PurdieDM.etal.Bevacizumabbeyondfirstprogressionisassociatedwithprolongedoverallsurvivalinmetastaticcolorectalcancer:resultsfromalargeobservationalcohortstudy(BRiTE).JClinOncol.2008;26(33):5326-34.


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Canadian Resources for Patients

CanadianCancerSociety.Availableat:www.cancer.ca.AccessedMay16,2011.

CanadianCancerSociety’sSteeringCommittee:CanadianCancerStatistics2010.Toronto:CanadianCancerSociety,2010.

CanadianPartnershipAgainstCancer:AnindependentorganizationacceleratingactiononcancercontrolacrossCanada.Availableat:www.partnershipagainstcancer.ca/.AccessedJuly4,2011.

ColorectalCancerAssociationofCanada.Availableat:www.colorectal-cancer.ca.AccessedJuly4,2011.

Formoreusefullinkstovariousresources,pleasevisitColorectalCancerAssociationofCanadaat www.colorectal-cancer.ca.

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2.CanadianCancerSociety.Availableat:www.cancer.ca/.AccessedOctober6,2011. 3.CanadianCancerSociety’sSteeringCommitteeonCancerStatistics.CanadianCancerStatistics2011.

Toronto,ON:CanadianCancerSociety;2011. 4.NationalCancerInstituteattheNationalInstitutesofHealth.Availableat:www.cancer.gov/.

AccessedOctober6,2011. 5.WhatYouNeedToKnowAboutCanceroftheColonandRectum.U.S.DEPARTMENTOFHEALTHAND

HUMANSERVICESNationalInstitutesofHealthAvailableat:www.cancer.gov/cancertopics/wyntk/colon-and-rectal/WYNTK_Colon.pdf.AccessedJuly4,2011.

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7.SauerR,BeckerH,HohenbergerW,etal.Preoperativeversuspostoperativechemoradiotherapyforrectalcancer.NEnglJMed2004;351:1731-40.

8.GerardJ,BonnetainF,ConroyT,etal.PreoperativeradiotherapywithorwithoutconcurrentfluorouracilandleucovorininT3-4rectalcancers:ResultsofFFCD9203.JClinOncol2006;24:4620-5.

9.BossetJF,ColletteL,CalaisG,etal,fortheEORTCRadiotherapyGroupTrial22921.Chemotherapywithpreoperativeradiotherapyinrectalcancer.NEnglJMed2006;355:1114-23.

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37.AndréT,BoniC,Mounedji-BoudiafL,etal.MulticenterInternationalStudyofOxaliplatin/5-Fluorouracil/LeucovorinintheAdjuvantTreatmentofColonCancer(MOSAIC)Investigators.Oxaliplatin,fluorouracil,andleucovorinasadjuvanttreatmentforcoloncancer.NEnglJMed.2004;350(23):2343-51.

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45.Camptosar®(irinotecanhydrochloridetrihydrateforinjection)ProductMonograph.PfizerCanadaInc. June29,2009.

46.FalconeA,RicciS,BrunettiI,etal.PhaseIIItrialofinfusionalfluorouracil,leucovorin,oxaliplatin,andirinotecan(FOLFOXIRI)comparedwithinfusionalfluorouracil,leucovorin,andirinotecan(FOLFIRI)as first-linetreatmentformetastaticcolorectalcancer:theGruppoOncologicoNordOvest.JClinOncol. 2007May1;25(13):1670-6.

47.MasiG,LoupakisF,SalvatoreL,etal.BevacizumabwithFOLFOXIRI(irinotecan,oxaliplatin,fluorouracil,andfolinate)asfirst-linetreatmentformetastaticcolorectalcancer:aphase2trial.LancetOncol.2010;11(9):845-52.

48.MarounJ,JonkerD,CrippsC,etal.PhaseIstudyoftheIXOregimen,irinotecan(I),capecitabine(X),oxaliplatin(O),asfirst-linetherapyformetastaticcolorectalcancer:Finalsurvivalresults.JClinOncol.2009;27:15s,(suppl;abstr4082).

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Ongoing Research and the Future of Treatment

OngoingresearchinCRChasleadtoadvancesintreatmentandnewwaysto managesideeffectsrelatedtotreatment,whichhelpedimprovedtheoutlook andqualityoflifeformanypeoplelivingwiththisdisease.

Alwaysinsearchofmoreeffectivetreatments,manyclinical trialsaredone totestdifferentcombinationsofdrugsthatarealreadyusedseparatelyto treatCRC .

OngoingresearchinCRCcanbefoundinClinicalTrials.gov,aregistryandresultsdatabaseoffederallyandprivatelysupportedclinical trialsconductedinthe UnitedStatesandaroundtheworld.ByvisitingClinicalTrials.govwebsiteatclinicaltrials.gov,youcanfindinformationaboutthepurposeofatrial,whomayparticipateinit,locationswhereitisbeingconducted,andphonenumbersfor moredetails.Thisinformationshouldbeusedtogetherwithadvicefromyourhealthcareprofessionals.

FormoreinformationaboutongoingresearchanddevelopmentinCRC, youcanalsovisitCanadianCancerEncyclopediafromtheCanadian CancerSocietyatinfo.cancer.caorColorectalCancerAssociationof Canadaatwww.colorectal-cancer.ca.

Where to find Support…

IfyouorsomeoneclosetoyouhasbeennewlydiagnosedwithCRCorin activetreatment,youdon’thavetogothroughthisalone.

CRCsupportgroupsexistinseveralcommunitiesacrossCanadawhichoffer meetingswherepatients,caregiversandfamiliescansharetheirexperiences, offerhelpandprovideinformation.Becauseeveryone’scancerexperienceis different,connectingwithotherswhoaregoingthroughsimilarexperiencecan helpyoulearnhowtodealwithmanyeverydayissues,maketoughdecisions andcopewitharangeofemotions.1,2

Help is available…

Canadian Cancer Society:Formoreinformationortofindasupportgroup inyourarea,contacttheCanadianCancerSocietybycallingtoll-freenumber at1-888-939-3333,orvisitthewebsitewww.cancer.caandclickon Support/Servicestab.1,2

Colorectal Cancer Association of Canada:Forinformationaboutsupport groupsinyourarea,calltoll-freenumber1-877-50COLON(26566),orvisitthe websiteatwww.colorectal-cancer.ca.1,2

Because

of ongoing

research, new

discoveries

help contribute

to constant

change in

knowledge and

understanding

of cancer. This

information

helps researchers

and healthcare

professionals

to develop

practices

in prevention,

detection and

treatment of

CRC, as well

as improving

the quality

of life of

people with

this disease.


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learning about colorectal cancerarchive.colorectalcancercanada.com/img/pdf/ccacbrochure... ·...

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