anemia in cancer (pit ipd)

7/23/2019 Anemia in Cancer (PIT IPD)

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Anemia in Cancer Patient:Anemia in Cancer Patient:Its Management and Role of ESAsIts Management and Role of ESAs

Budi D MachsoosBudi D Machsoos

Hematology - Medical Oncology DivisionHematology - Medical Oncology DivisionDept. of Internal MedicineDept. of Internal Medicine

Saiful Anwar eneral Hospital !Saiful Anwar eneral Hospital !

Brawi"aya #niversity$ %aculty of MedicineBrawi"aya #niversity$ %aculty of Medicine



IntroductionIntroduction

Anemia is a common complication inpatients with cancer and cancertherapy.

&he anemia symptoms impactspatient's (uality of life )*o+,$ and

aects tolerance of treatments$resulting in the delayed schedule orreduced intensity of the treatments..

1. Leonard RC, et al. Annals of Oncology 2005.16: 817–824,2. Stacy R, et al. The Oncologist 2005;10:539–554




Its prevalence varies with cancer type$ stage$and therapy used. .$/

1. Stacy R, et al. The Oncologist 2005;10:539–5542. Leonar R!, et al. "nnals o# Oncology 2005.1$: %1&–%24

3. L'(ig ", et al. )loo, 1994. %4*4+ :105$10$3

Malignancy Anemia Prevalence (%)

Hematologic Malignancy 72

Cervix carcinoma 82

Colorectal cancer 67

Lung Cancer 63

Other solid tumor 66




Depending on the type of malignancyand chemotherapy employed$ up to001 of patients developed mild ormoderate anemia )H2 3 g4dl, andup to 501 of patients developedsevere or life-threatening anemia )H2

36.7 g4dl,./



Definition and severityDefinition and severity

-O an /! criteria #or seerity o# aneia-O an /! criteria #or seerity o# aneia

Seerity -O *gl+ /! scaleSeerity -O *gl+ /! scale

*gl+*gl+

r.0 */one+r.0 */one+ 11 /oral 611 /oral 6

r.1 *7il+ 9,5 – 10,9 10,0 –r.1 *7il+ 9,5 – 10,9 10,0 –

/oral/oral

r.2 *7oerate+ %,0 – 9,4 %,0 – 10,0r.2 *7oerate+ %,0 – 9,4 %,0 – 10,0

r.3 *Seere+ $,5 – &,9 $,5 – &,9r.3 *Seere+ $,5 – &,9 $,5 – &,9r.4 *Li#eThreatening+ 8 $,5 8 $,5r.4 *Li#eThreatening+ 8 $,5 8 $,5

/!!/ 'ieline, 200&

8 9ormal: ;-5 g4d+ for men$ /-< g4d+ for women



Persistent

recurrent disease

!e"ly diagnosed

In remission

# $# # &# '# # #

*verall

Patients "it+ anemia (%)Anaemia: ,- .$ gdl at enrolment

Euro/ean Cancer Anaemia Survey (ECAS)0 1ud"ig et al2 Ann Oncol ##3 $& (Su//l ): $4 5A&PD6

&$%

&%

'7%

&4%

Incidence of AnemiaIncidence of Anemia

in Cancer Patientsin Cancer Patients



Incidence of Anemia in Patients "it+ solid 8umorsIncidence of Anemia in Patients "it+ solid 8umors

9ndergoing C+emot+era/y9ndergoing C+emot+era/y

SC1C: smallcell lung cancer3!SC1C: nonsmallcell lung cancer ;roo/man < Itri2 JNCI $4443 4$: $$=&'

#

$##

&#

'#

##

>#

S C 1 C

* v a r i a n

? r e a s t

! S C 1

C

, e a d

< ! e c @

C o l o

n

7#

4#

P a t i e n t s " i t + a n e m

i a ( % )



AnemiaReduced

a-ility to

"or@

De/ression

Im/aired social

function

atigue

SeBual

dysfunction

Poor

concentration

Reduced

eBercise

ca/acity

Anemia su-stantially decreasesAnemia su-stantially decreases

uality of 1ifeuality of 1ife



Anemia

A-normal iron

meta-olism

?one marro"

infiltration

Decrease ofEryt+ro/oietin

/roduction

!utritional deficiency

(ironvitamin ?$ folic acid)

Renal im/airment

Malignancy

itself

1ud"ig et al2 Hematol J ##3 &: $$=&#

ood < ,rus+es@y2 J Clin Invest $443 4: $#=4

Mercadente et al2 Cancer Treat Rev ###3 : &#&=$$

Myelosu//ression -y

c+emo andor

radiot+era/y

?lood loss

,emolysis

Cause of Anemia in Patients withCause of Anemia in Patients with

CancerCancer

Present of

Infection

Immune sytem

activation0

inflammation

S+ortened survival

of Eryt+rocyte



"ctiatei'nesyste

"neia

Shortene

s'rial

"neiain'cing

s'stance

RCs

Re'ceO

<ro'ction

<aireiron

'tili=ation

S'<<resse)>?!>?

!"#rythro<hagocytosis

@yserythro<oiesis

$#"%γ$L%1

!"# 1%ant&try's&n

$#"%γ$L%1

!"#

$L%1 ,!"#

7acro<hag

es

T'orcells

"o(ro)s&an * et al. $n: +yt- #, et al, eds. r-/ryt-ro'o&et&n &n cancers)''ort&e treatent. "e( or, ": *arcel 3eer $nc 16:1%4.

Etiology of CancerRelatedEtiology of CancerRelated

Anemia Is MultifactorialAnemia Is Multifactorial



Management */tionsManagement */tionsfor Anemia in Patientsfor Anemia in Patients

"it+ Cancer "it+ Cancer

Trans#'sion AATrans#'sion AA

ororS"s AAS"s AA



*/tions for Anemia in Cancer*/tions for Anemia in Cancer

PatientsPatients

!o treatment

(#%)

8ransfusion

($%)

Iron alone(>%)

ESAs($7%)

1ud"ig et al2 Ann Oncol #$3 $& (Su//l ): $4 5A&PD6



8ransfusion in Anemia8ransfusion in Anemia

"ssociate (ith serio's sie eBects"ssociate (ith serio's sie eBects22

*iron oerloa, i'nos'<<ression,*iron oerloa, i'nos'<<ression,

heolysis, in#ections+heolysis, in#ections+

ergency treatent #or ac'te, seereergency treatent #or ac'te, seereaneiaaneia

?s'ally not gien 'ntil sy<toatic?s'ally not gien 'ntil sy<toatic

seere aneia * %seere aneia * %–9 gl+–9 gl+

Bects are ieiate, 't transientBects are ieiate, 't transient

an 'ns'stainalean 'ns'stainale11

$2 illiamson et al2 BMJ $4443 &$4: $=$4

2 ensen et al2 Blood ##&3 $#$: 4$=



Advantages of ESAs overAdvantages of ESAs over

8ransfusion8ransfusion

can 2e used for treatment of mild-to-can 2e used for treatment of mild-to-moderate anaemiamoderate anaemia$ /$ /

produce smooth and sustained increase inproduce smooth and sustained increase in

H2H2==

improve *uality of +ife 2y maintaining higherimprove *uality of +ife 2y maintaining higherH2 targetsH2 targets

are well toleratedare well tolerated

are more convenient than transfusionsare more convenient than transfusions Induce red 2lood cells that function normallyInduce red 2lood cells that function normally

$2 1ud"ig et al2 Hematol J ##3 &: $$=&#

2 RiFFo et al2 J Clin Oncol ##3 #: '#7&=$#>

&2 1ud"ig et al2 N Engl J Med $44#3 &: $4&=4



ESAs and Mec+anism of actionESAs and Mec+anism of action

>rythropoietin is a glycoprotein )M?: =0@Da,$ that role as hematopoietic growthfactor produced primarily in the @idney)renal peritu2ular 2ro2lasts, andrenal peritu2ular 2ro2lasts, and

transported via 2loodstream to 2onetransported via 2loodstream to 2onemarrowmarrow

>Sas interacts with specic receptor onspecic receptor on

erythroid progenitor cells in the 2onemarrow to stimulate erythropoiesiserythropoiesis

$2 MaFFa 0 $442

2 is+er2 Exp Biol Med ##&3 7: $=$'



?enefits of ESAs in Patients?enefits of ESAs in Patients

Receiving C+emot+era/yReceiving C+emot+era/y

BenetsBenets orrection of H2 levelsorrection of H2 levels

Ceduction in re(uirement for red 2lood cellCeduction in re(uirement for red 2lood cell

transfusionstransfusions Improvement in (uality of lifeImprovement in (uality of life

%lei2ility and convenience%lei2ility and convenience

SafetySafety Co2ust analyses of IA studies$ including 2othCo2ust analyses of IA studies$ including 2oth

study-level and patient-level meta-analyses$study-level and patient-level meta-analyses$

support the neutral impact of >SAs on OSsupport the neutral impact of >SAs on OS



>vidence-2ased guidelines recommend H2 levels 2e maintained2etween and /-= g4d+ during erythropoietic therapy

Summary of International EvidenceSummary of International Evidence

?ased ;uidelines for 8reating CIA?ased ;uidelines for 8reating CIA

Recommendation ASC*AS,5$6 !CC!56 E*R8C5&6

Initiate ESA t+era/y

,- G $# gd1(clinical decision if ,- H $# to G $ gd1)

,- G $$ gd1 ,- 4$$ gd1(clinical decision if,- G $$24 gd1)

;oal of treatmentMaintain ,- at ornear $ gd1

Maintain -et"een$#$ gd1

8arget ,- s+ould-e $$$& gd1

1. R&o 3, et al. Cl&n Oncol. 200826:12%14.2. "CC" Cl&n&cal ract&ce 9)&del&nes &n Oncology.

Aa&lale at: -tt':;;(((.nccn.org. Accessed *ay 28, 2008.. oeeyer C, et al. /)r Cancer. 200440:2201%2216.



3ecrease &n o<ygen del&ery to t-e&dneys

er&t))lar &nterst&t&alcells detectlo( o<ygen leels &n t-elood

roeryt-rolasts &n

red one arro(at)re ore =)&cly&nto ret&c)locytes

*oreret&c)locytes

enter c&rc)lat&nglood

Larger n)er ofRCs &n c&rc)lat&on

$ncreasedo<ygen del&ery

to t&ss)es

Ret)rn to -oeostas&s (-enres'onse r&ngs o<ygen del&ery to

&dneys ac to noral

/O

er&t))lar&nterst&t&alcells secrete /O&nto t-e lood

*)lca-y L. +e&n Oncol. 200128>2 s)''l 8?:1%2.

8+e P+ysiologic Role of ESAs8+e P+ysiologic Role of ESAs



Eryt+ro/oiesisEryt+ro/oiesis



ESAs:ESAs: site of action

Eryt+ro/oietinEryt+ro/oietin

Eryt+ro-lasts

Reticulocyte

?9E C9E

A/o/tosis

"it+out

eryt+ro/oietin

?9E: ?urstorming 9nitEryt+roidC9E: Colonyorming 9nitEryt+roid

Red -lood cells

is+er 2 Exp Biol Med ##&3 7: $=$'



Dose of ESADose of ESA

Note: This table includes new doses contained in the FDA-approved label as

released on November 8, 2007 E. Douglas CiFFo$et al. E lin Oncol./005$ /<:-5

@ose an@ose anoiCcationsoiCcations

<oetin "l<ha<oetin "l<ha

nitial osenitial ose 150 ?DgS.! T-150 ?DgS.! T- 40,000 ? S.! (eeDly40,000 ? S.! (eeDly

@ose increase@ose increase ncrease ose to 300ncrease ose to 300?Dg S.! T- i# no?Dg S.! T- i# no

re'ction inre'ction intrans#'siontrans#'sionreE'ireents or risereE'ireents or rise

in a#ter % (eeDsin a#ter % (eeDs

ncrease ose to $0,000ncrease ose to $0,000? S.! (eeDly i# no? S.! (eeDly i# no

increase in y F 1increase in y F 1gL a#ter 4 (Ds o#gL a#ter 4 (Ds o#thera<y, in the asencethera<y, in the asence

o# R)! trans#'siono# R)! trans#'sion

@ose re'ction@ose re'ction @ecrease ose y 25G (hen reaches a leel@ecrease ose y 25G (hen reaches a leel

neee to aoi trans#'sion o# increases neee to aoi trans#'sion o# increases 1 gL in 2 (Ds1 gL in 2 (Ds

@ose@ose

(ithholing(ithholing# eHcees 12 gL, (ithhol ose 'ntil # eHcees 12 gL, (ithhol ose 'ntil

a<<roaches a leel (here trans#'sion ay ea<<roaches a leel (here trans#'sion ay ereE'ire. Restart ose at 25G elo( <reio'sreE'ire. Restart ose at 25G elo( <reio's

oseose



Dose of ESADose of ESA

@ose an@ose anoiCcationsoiCcations @are<oetin "l<ha@are<oetin "l<ha

nitial osenitial ose 2.25 cgDg S.! (eeDly2.25 cgDg S.! (eeDly 500 cg S! eery 3500 cg S! eery 3(eeDs(eeDs

@ose increase@ose increase ncrease ose to 4.5ncrease ose to 4.5cgDg i# there is 8 1cgDg i# there is 8 1gL increase in a#tergL increase in a#ter$ (eeDs$ (eeDs

@ose re'ction@ose re'ction @ecrease ose y 40G o# <reio's ose (hen@ecrease ose y 40G o# <reio's ose (hen reaches a leel neee to aoi trans#'sion reaches a leel neee to aoi trans#'sion

or increases 1 gL in 2 (eeDsor increases 1 gL in 2 (eeDs

@ose@ose(ithholing(ithholing

# eHcees 12 gL, (ithhol ose 'ntil # eHcees 12 gL, (ithhol ose 'ntil a<<roaches a leel (here trans#'sion ay ea<<roaches a leel (here trans#'sion ay ereE'ire; restart ose at 40G elo( <reio'sreE'ire; restart ose at 40G elo( <reio'soseose

Note: This table includes new doses contained in the FDA-approved label asreleased on November 8, 2007

E. Douglas CiFFo$et al. E lin Oncol./005$ /<:-5



Pre/aring of ESAs t+era/yPre/aring of ESAs t+era/y

%erritin G 00 g4+

&ransferin saturation G /01

9o severe hypertension. B should 2e

controlled prior to initiating therapy withepoetin

%or 2etter response H2 level should 2e GJ

5 g4dl



Delayed orDelayed or diminis+ed res/onse to

r,uEP*

If delayed or diminished response to rHu>O occurs$the following etiologies should 2e considered:

Iron deciency: all patients will eventually re(uiresupplemental iron therapy.

#nderlying infections$ inKammatory or malignantprocesses. Occult 2lood loss. #nderlying hematologic disease. Litamin deciencies: folic acid or vitamin B-/. Haemolysis. Aluminum intoication.



Adverse events of ESAsAdverse events of ESAs

Shoc@Shoc@

ardiovascular: tachycardia$ardiovascular: tachycardia$

hypertensive encephalopathyhypertensive encephalopathy

ere2ral em2oliere2ral em2oli

S@in rashS@in rash

I&: nausea$ vomiting$ diareI&: nausea$ vomiting$ diare

+iver: SO&4S&4+DH4A+ increase+iver: SO&4S&4+DH4A+ increase

"CC" 9)&del&ne, 2007



Contra indicationContra indication

Hypersensitive to >SAs or itsHypersensitive to >SAs or its

componentcomponent

#ncontrolled hypertension#ncontrolled hypertension

Hypersensitive to human al2uminHypersensitive to human al2umin

a



SummarySummary

Anemia is a most common complication inpatients with cancer and cancer therapy.It impacts patient's *o+$ and aectstolerance of treatments.

Management OptionManagement Option of anemia in cancerof anemia in cancerpatients are CB transfusion or >SAs.patients are CB transfusion or >SAs.

Since /00/ ASO and ASH haveSince /00/ ASO and ASH haverecommended >SAsrecommended >SAs to treat anemia into treat anemia in

cancer patientscancer patients >SA is eective for reducing transfusion

re(uirements and improving *o+ inpatients with cancer.

anemia in cancer (pit ipd)

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