Experience in the use of human recombinant erythropoietin (rHuEPO) in cancer patient with anemia

Med J Indones

40

Tambunan

Experience

in

the

Use

of

Human

Recombinant

Erythropoietin

(rHuEPO)

in

Cancer Patient

with

Anemia

Karmel

L.Tambunan,

Aru

Sudoyo,

A.Harryanto

Reksodiputro *

Abstrak

Anemia pada pendeita kanker dapat disebabkan berbagai faktor seperti toksis sitostatika pada sumsum tulang, defsiensi besi, asamfol.at,hemolitikdanperdarahan.Anemiaini seringdiserlai'kadareitropoitinyangrelatifkurang. Atasdasarkenyataantersebut

di aàs

diharapkan pem-berian eitropoietin pada

peiderita

kanker al<nn dapat lebih merangsang erifto-poiesis dan menaik*an hemoglobin. pasien yang

diteliti

yaiti p"ndiita

kanker yang sedang mendapat kemoterapi disertai anemia, dan penyebab anemia bukan karena hemolitik, defisiens[ besi, àefisiensi asamfotat dàn defsiensi Btz.. Pasien yang dileliti terdiri dari

]

knsus Ca nasoJaring, 2 kasus limfomamalignumâan2 kasus mu[tiplemyeloma. Pasien diberirHuEPo 150 iu/kg, subkutan 3 kali seminggu, selama I6 minggu' Dilakukanpemeriksaanhemoglobin(Hb)danhematokrit(Ht)tiapminggudanpadamingguke-l2ditemukan kenaikanHb>2gvodan

Ht >

6vo pada 4 t<,,sus (gyvo*) dan pada satu kasus walaupun kenaikan Hb

<

2 gEo tetapi menjadi bebas

dari

kebutuhan transfusi' pemberian rHuEpO seperti tersebul di otot dapat meningkatkan hemoglobin penderita kanker dengan anemia.

Abstract

Anemia in cancer patients can be the result of a variety of

factors,

often in combination. The chemotherapy-related myelosup' pression

is

logically the main cause, but other condi.itions sometimes prevail, such as iron or folate deficiency, hemolysis, bleeding, or, as mentioned before, the combination of the above, Known as ane nia of cancer or chronic disease, it is heralded by the disturbance

of

iron utilization and, recently, found to be accompanied by low eryIhropoetin levels.

It

is with the latter condition in mind that we have undertaken

a

study ,o

orrrri

i"rponsiveness of the anemia of cancer to erythropoetin,

in

this case the human recombinant erythropoetin (rHuEpO). Five cancer patients withvarying types of cancers who have undergone chemotherapy were recruited, and received THuEPO 150 iu/kg, thrice weekly subcutaneously

for

a

peiod

of 16 weeks. Hemoglobin levels and hemalocrit were monitored and at 12 weeks was noted an increase in hemoglobin

i"i"k

by

^or"

than 2 g/dl and hematocrit measurement by more than 67o in 4 cases (80Vo). one case

had

increases less than'the aforemeniioned but was made transfusion-free. We conclude that

rHuEPo

has

an

impressive he mo g lo b in- increas i n g efe ct.

Keywords

:

erythropoietin, anemia, ancer patient.

level

of

endogenous

erythropoietin

(EPO) that

are

in-appropriately

low for

the

degree

of

the

anemia,

a

blunted EPO

response

to hypoxia

and

low

red

blood

cell production.

The

concentration of erythropoietin

in

the serum cancer

patients

is lower

that

expected

com-pare

to patients

with iron deficiency un"-iu.2

Several studies groups have

reported

that

recombinant

human

eritropoietin (rHuEPO)

is

able improved

anemia

in

cancer patient.3

These

early

observations

led to

the conclusion

that

THuEPO

could

be

beneficial

for

cancer patients

with

anemia. The aim

of

this study is to evaluate the

efficacy

of of

the

use

of

THuEPO

in

anemic

cancer patients

undergoing chemotherapy.

Anemia

is a

problem in

patients

with

advanced cancer'

Blood transfusion may

be required

in

many

of

these

patients,

particularly

those

undergoing chemotherapy'

Anemia

in cancer maybe

multifactorial

in etiology

and can be caused

by

a

variety of

conditions,

among these

are, i.e., iron

or folic

acid deficiency, hemolysis

or

bleeding.

In

the

cancer patient receiving

chemo-therapy,

the anemia can be aggravated by the effects

of

cytostatic-rel

ated

myelosuppresion.

Generally,

the

type

of

anemia

in

cancer

patients

is

of

the chronic disorder

type,l

characterized

by

serum

Vol6, No

I,

January - March 1997

MATERIALS

AND METHODS

The study design

will

be an

open label,

non

compara-tive

evaluation

of

the eficacy

and safety

of

sub-cutaneous THuEPO administration

in

patient with

anemia

secondary

with

malignancy

been treated by

cyclic

chemotherapy. Patient were enrolled

in

the

study

if

they

fulfil

the

inclusion

crireria.

Criteria of

cancer patients

included in

the study

were

non leukemia malignancy; hemoglobin

<

10,5

g/dl;

iron,

folate,812

deficiency,

hemolysis

and

bleeding

ruled out

as causes

of

anemia;

patient

still

undergoing

chemotherapy;

no

acute

illness

in

the last

7

days;

no

radiotherapy

in

the last 30

days;

life

expectancy

of

6

months or

more;

performance score

of

0,I,2,

or

3,''l

(WHO

performance

status);

informed

consent.

The patients

underwent complete

physical

and

laboratory examinations, which

included

hemoglobin,

hematocrit, reticulocyte

count,

WBC,

platelet count,

ureum, creatinine, serum

iron,

total

iron

binding

capacity,

glucose,

total

protein,

folic

acid,

Bl2,

Coombs

test,

stool

hematest, and

prothrombin

time.

Table

l.

Response to THuEPO in 5 cases of anemic cancer patients

Human Recombinant

Erythropoietin 4l

Those

eligibte for

study wers

started

on

150

u$its

_Der

kg bodyweight

of

recombinanr

human erythrpoietin

(rHuEPO)

three

times

a

week.

The patients were

then

monitored

with weekly

examinations

of

hemoglobin,

hematocrit,

and

reticulocytes. Side effects,

if

present,

were noted.

A response was

defined

as an increase

in

hemoglobin concentration

of

at

least 2

g/dl

within

12

weeks,

or

increase

in

hematocrit

by

more than

6

per-cent

in

l2

weeks.

RESULTS

The

trial

was started

in August

1993.

Five

cases \r/ere

able

to

be

included

in

the study,

consisting

of

I

case

with

nasopharyngeal cancer stage

III

undergoing

chemotherapy

with platinum

and

epirubicin,2

cases,of

non-Hodgkin lymphoma, both

stage

III,

at that

time

on the

CHOP chemotherapy regimen,

₂ cases

of multiple

myeloma,

at stages

II

and

IIIA,

respectively,

and

who

were receiving

melphalan

and

prednison. One

of the

multiple

myeloma

cases was

requiring

packed red

cell

transfusions every month (Table

I

and

Figure

l-6

showed response

to treatment

with

THuEPO).

undergoing chemotherapy

Weeks

l6

t4 t2

l0

Ca Nas female 35 years old

LNHa

female

2l

years old

LNH female 30 years old

MM

female 62 years old

MM

female 68 years old

t4.4

43

9.6 I 1.5

35

t2.2

t24

Hr

27 31

37

Hb

9.6 t0.5

I

I

5

to.2 8.8 Hb I1.6 35 10.7 t2.5 38 10.2

3l

13.2 13.8 42 12.6 t2.2 36 I1.0 34 13.2 39 12.8 39.6 9.3 28

Hr 29

32

Hb 8.2

tO 2

Hr

25

Hb

8.9

32

r0.8

34

33

ll2

12

Hr

26

32

34

36

Hb

8.0 7.0

8.0

7.8

35 11.2 38 12.5 38 I 1.6 35 8.2 24 38

l3

39

38

124

t4

4t

9.8

27

38

42

7.2

9.0

21

29

13.4

40

r 3.5

30

10.7

23 24

20

Mean

l0

6

l0.l

32

8

31.8 Hb

Ht 26.28.7 9.7 29 10.8 33.6 12.2 37.2 10.8 33.4 11.7 35. r

9.8 36

[image:2.595.43.547.406.792.2]

Med J Indones

42

Tmùman

50

40'

30

20

10

o

16

14

't2

10

I

t

4

2

0

246810121416

[image:3.595.57.556.66.732.2]

Weeks

Figure

L

Case no. I, female, 35 years old, Cancer Nasopharynx

2468't0

12 14

16

Weeks

Figure 2. Case no. 2, _female, 21 years old, Limfoma non-Hodgkin

Hb

2468101214

Weeks

Figure 3. Case no. 3, rnale, 30 years old, Limfoma non-Hodgkin

Hb

HI

14

12

10

I [-;bl

u

l*t'

I

4

2

0

't4

12

10

I l-

HËl

u

l*t,

I

4

2

VoI6, No

I,

tanuary - March 1997 _{H uman R ec omb inan t Ery throp oi}

e tin 43

't6

14

12

10

I

6

4

2

0

2468101214

[image:4.595.57.557.61.749.2]

Weeks

Figure 4. Case no.4, male, 62 years old, Muttiple Myeloma

Ht 30

25

20

15

10

5

o

Hb

12

10

I

6

4

2

0

14

12

10

I

l;Hbl

.

l*t,

I

4

2

0 Ht

2468101214

₁₆

Weeks

Figure 5. Case no. 5, male, 6g _{years old, Multiple Myeloma}

a a

4

6

''= I

10

12 Weeks

Figure 6. Mean Hb, Ht,from 5 cases

Hb

40

30

20

M

Tambunan

DISCUSSION

made

transfusion-free

increased

the

response

to

actually

seen

by

the

second week.

This finding

was

t

in which

resPonse was

studied.T

This difference

r's inclusion of

leukemia

and

myelodysplastic patients

in

that study,

as the

two

entitiés

havJ

been

known

to

respond

poorly

to

erythropoetin, the

same reason

for

the exclusion

of

puti"ntt in

our study'

In

a

review compiled

from

12

medical institutions, 616 patients on

cancer

chemo-therapy were studied,

in

which

l27o werc

receiving

transiùsions

for

anemia.8

In

this

study one

patient

was

rendered

transfusion-free

after THuEPO

treatment'

The

others

reported

that

treatment

with

THuEPO

reduced

both

anemia

and transfusion requirement

in

anemic

patients

with

cancer'9' lo

It

seems that

future

studies

in

the use

of erythropoietin

will

have

to

take

into

consideration factors

or

parameters that

can

influence

response'

That

s and

found

that

ant

role

in

pred

erum levels

of I

increase

in

of cancer

involved will

have to be taken

into

considera-tion. From this study

we have

drawn

these

conclusion:

1)

The administration

of

THuEPO

in

a

dose

of

150

mg/kg

BW

in

cancer patients undergoing

chemo-Med J Indones

therapy

resulted

in

an

increase

flb

>

2 gldl

and

hematocrit by

more than

6

percent

(in

80 percent

of

cases).

2)

Response

to

treatment was

noted at week 2 with

maximum

increase bY

week

12.

3)

In

one case

with multiple

myeloma

the

patient

was

freed

from

transfusion requirement.

4)

Cases

with

naso-pharyngeal cancer,

non-Hodgkin's

lymphoma,

and

multiple

myeloma

have

good

hop"

of

attaining

a

good response

with

iffuBpO

when the

previously

mentioned

inclusion

criteria

were

used.

REFERENCES

l.

Bun HF.

Anemia associated

with

chronic. disorders' In

Harrison's Principle of Internal Me'dicine

1lù

edition' New

York: McGraw

Hill

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2.

Miller

C,

Jones

RJ, Plantodasi's

et

al'

Decreased

Eryhtropoietin response in patients with the anemia of

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3. Abel R. Erythropoietin for Anemia in Cancer Patient : Eur

I

Cancer 29 A. SuPPI

2'

1993,52-8'

4. Bowen D, Culligan D, Jacob A. The treatment of anemia in

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with

recombinant human

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l99l;77:419-33'

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t

uOwig

H, Frizt E,

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M

et

al'

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Ann

Onc

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M,

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E'

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IM

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RM. Clinical

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erythropoietin (rHuEPO),

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the treatment

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anemia

as-sociated with cancer. Eryhtropoiesis 1994, 5, 108-14'

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3,21-8-I

l.

Thatcher N. Predicting the response to THuEPO in anaemic