: 57 3 1999

- TTS

= A b s t ra c t=

E v a lu a t i o n o f e f f i c a c y a n d s a f e t y o f f e n t a n y l - T T S i n a d u lt p a t i e n t s
w i t h c a n c e r- re la t e d p a i n

B o k K e u n L e e , M .D ., C h i W o n S o n g , M .D ., J in N o P a r k , M .D .
S u k - K u C h o , M .D . J a e Y o o K im , M .D ., Y o u n g S e o n H o n g , M .D .
H o o n K y o K im , M .D . a n d K y u n g S h ik L e e , M .D .

D e p ar tm e n t of I n t e r n al M e d icin e ,
C o lle g e o f M e d icin e , C at ho lic U n iv e r s ity , S e ou l, K or e a

B a c k g ro u n d : T h e t ra n s d er m a l a d m in is t ra t ion of n a r cot ics is on e of th e a lt er n a t iv e w a y s of

p r ov id in g a d eq u a te p a in re lief for t h e p a t ien ts w it h ch ron ic ca n ce r pa in . A P h a s e 4 tr ia l w a s
c on d u ct ed t o e v a lu a t e t h e e ffica c y a n d s a fet y of F e n t a n y l- T T S in a d u lt pa t ien t s w it h ca n ce r- r ela te d
p a in in K or e a .
M e th o ds : P a tie n t s w ith h is t olog ica lly c on fir m ed m a lig n a n cy , w h o h a v e pa in r ela te d t o t h e c a n c er
a n d/ or th er a p y , pa in n e c es s it a t in g t h e u s e of opoid a n a lg es ics , a g e of 18 y r or old e r, a b ilit y t o
c om m u n ic a t e effe ct iv e ly w it h s t u d y p er s on n e l, a n d s ig n e d on in for m e d c on s en t w er e in c lu d e d . T h e
p a tie n t s w e r e tit r a t ed w it h a s h or t - a c tin g n a rc otic t o c on t r ol th eir c a n c er p a in b e for e th ey a r e
c on v e r te d to a fen ta n y l- t ra n s d er m a l t h e ra pe u t ic s y s te m (T T S ). S h ort a ct in g p a r en t er a l m orp h in e a n d
M S c on t in w er e u s ed a s r es c u e m e d ica tion s . A ll p a t ien t s w e re e v a lu a t ed in it ia lly a n d w er e follow ed
u p w it h a pa in v is u a l a n a log u e s c a le(V A S ), qu a lit y of life( Q O L )- V A S . P a tie n t s w e r e a s k e d t o k eep
t h e d a ily r ec ord for 21 d a y s a b ou t p a in V A S , Q O L- V A S , a m ou n t of re s c u e m or ph in e u s e d , a n d s id e
e ffe ct s .
R e s u lts : T w e n t h t w o pa t ien ts w e re en rolle d fr om J a n u a r y 1996 to O c t ob e r 1997. T h e d os e of
fe n t a n y l- T T S r eq u ir e d , r a n g e d b e t w e en 25 a n d 75 u g / h r (25 / h r in 13, 50 / h r in 4, a n d 75 / hr
in 2). T h e m e a n d os e of m orp h in e r eq u ir ed b e for e t h e u s e of th e fen ta n y l- T T S w a s 135.3 m g (20- 285
m g / d a y ), b u t it w a s d e cr e a s ed a fte r th e u s e of th e fen ta n y l- T T S . P a in V A S a n d Q O L- V A S w er e
in a d q u a te lev e l d u r in g t h e fen ta n y l- T T S trea tm ent. P at ien ts fa v ored continu ou s us e of fe n t a n y l a fte r
t h e s tu d y w a s fin is h ed . S id e effe ct of fen t a n y l- T T S w a s m in im a l.
C o n c lu s io n : T ra n s d er m a l fen ta n y l s ee m s to b e a c on v e n ie n t a n d effec tiv e a n a lg e s ic for t h e
c on t r ol of c a n ce r r ela te d p a in in K or ea n . A c on t r olle d t r ia l com p a r in g fe n t a n y l- T T S t o m or ph in e
n ee d s to b e follow ed . ( K or e a n J M e d 57:348- 356, 1999)

K e y W o rd s : F e n t a n y l- T T S , P a in c on t r ol, C a n ce r

: 1999 5 31
: 1999 6 7
: , 62 (150- 010)
E- m ail : y 331@ch ollian .n et

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 Bok K eun Lee, et al : E v aluation of efficacy and s afety of fentany l- T T S in adult pat ient s w it h cancer- relat ed pain

7).
B on ica 8) 60- 80%
1959 , F oley 9)
(d r operid ol)
(n eu r olept a n a n a lg es ia ) . ,
1), - ,

2). 10-12).
P C A ( P a tien t C on tr olled A n a lg es ia)
.
, ,
. 13, 14).
2),
, - 3). ( n on - in v a s iv e t ra n s d er m a l)
4),
4, 5). .

. ( in t ra v en ou s ),
(in tr a m u s cu la r ) (s u b cu t an eou s ly ) .

( recta l s u p pos it or y ), (s h or t- actin g )

, (s u b lin g u al) . .
8 12 (s u s ta in ed -
relea s e for m ) .

1.
(b r ea k t h r ou g h p a in )
. 1

, .
, (r es cu e
m or ph in e) ,

, V is u al A n a log u e S ca le (V A S )
6).
( T r a n s der m a l T h er a- .
peu tic S y s t em , T T S ) , ,
. 3 ( F ig u r e 1),
, /
, , , ,
72 , ,

- 34 9 -
 : 57 3 469 1999

,
, ,
, 3
. .
. ( ) ,

.
. 7
, 2.

( VAS 5.0) 1)
, 2)
. , 3) 1
, 2 404 m g 404 m g
(
VAS 5.0), , 4) 18 , 5) 2
. , 6) , 7)
1 404 m g
VAS .
5.0 1)
. 21 , 2)
. 1 , 3)
(T a b le 1), 3 , 4) (C O 2 ret en tion )
, 5) 2.0
T a b le 1 . F e n ta n y l do s e pre s c rip tio n b a s e d o n d a ily
m g / d l(30 m ol/ L ) , 6)
m o rp h in e e q u iv a le n c e d o s e
2.0 m g / d l(177 m ol/ L ) , 7)
O r a l 24h r m o r p h in e F en ta n y l
(m g / da y ) (ug /hr)
(T a b le 2).
134 25
1) 1 8
135- 22 4 50
, 2)
225- 31 4 75
315- 40 4 100 (v er b al s tim u la tion ) , 3)

F ig ure 1. Du r in g th e pa t ien t s elec tion a n d s t a b iliza t ion ph a s e, S R M w a s u s ed for pa in

c on t r ol, a n d it w a s s w it ch ed ov e r t o fen ta n y l- T T S on d a y 0. F en t a n y l- T T S w a s
c on t in u ed t h r ou g h ou t th e op en tr e a t m e n t p h a s e tog et h er w it h r es c u e m orp h in e.

- 35 0 -
 7 : -TTS

T a b le 2 . In c lu s io n a n d e x c lu s io n c rite ria

1 . In c lu s io n C r it e r ia
1) a h is t o lo g ic a lly c on fir m e d m a lig n a n c y
e it h e r r e c u r r e d a ft e r p o t e n t ia lly c u r a t iv e t h e r a p y o r
is n o t a m e n a b le t o c u r a t iv e t h e r a p y a t p r e s e n t a t io n
2 )p a in c a u s e d b y m a lig n a n c y d is e a s e
3 )p a in t h a t r e q u ir e s n o m o r e t h a n 4 04 m g o f o r a l m o r p h in e d a ily
4) a t le a s t 18 y e a r s o f a g e
5) a n e s t im a t e d s u r v iv a l o f a t le a s t 2 m o n t h s .

2 . E x c lu s io n C r it e r ia
1) h is t o r y o f a lle r g y t o o p io id
2) a h is t o r y o f n a r c o t ic a b u s e
3) a c t iv e s k in d is e a s e
4) a h is t o r y o f C O 2 r e t e n t io n
5) r a d ia t io n t h e r a p y fo r a ll p a in fu l s it e s
w it h in 3 0 d a y s o f e n t r y in t h e s t u d y
6) a s e r u m b ilir u b in e > 2.0 m g / d l
7) s e r u m c r e a t in in e le v e l > 2.0 m g / d l
8) a n y c o - e x is t in g m e d ic a l c o n d it io n

VAS
, 4)
, 5) VAS
, 6) 12 -TTS 1 .
, 7)
. 2)
3 (72 )
3. 3 3
1) .
1 , .
/ , 2
. 25 u g / h r , 1
90 m g ( 30m g )
, , 25 u g / h
. . 1 90 m g
( 30 m g )
,
( . ,
)
. 12 25 u g / h .
1 ( 25 u g / h 2
. 50 u g / h 1 ).

- 35 1 -
 K ore a n J ou rn a l of M e dic in e : V ol. 57, N o. 3, 1999

3) " " " "

VAS .
VAS
.
. 1 , 21
( ) 4
( , , , ) .
. ,
, 5.

pa ired T - t es t
, , p < 0.05
.

.
. . , , 1
21 1 ,
, 9 , 21 .
. C h i- s q u ar e tes t ,
p < 0.05 .
4.

1) 15
(
) 22 3
. 1 13
. , 1
(V A S ), , 1 .
(V A S ), 15 3
19 . 25 u g / h r
. 13 50 u g / h r 4
75 u g / h r 2 .
2) 25 u g / h r 50 u g / h r 1
50 u g / h r 75
ug/ hr 1 (T a b le 3).
. , ,
1 21 1)
1 , 9 , 21 .
VAS 135.3m g (20- 285 m g / d ay )
. VAS 10 cm 20m g
. (0- 225m g ) ( F ig u r e. 2). -TTS
VAS . 1 57 u g / h r

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 Bok K eun Lee, et al : E v aluation of efficacy and s afety of fentany l- T T S in adult pat ient s w it h cancer- relat ed pain

T a b le 3 . F e n ta n y l- T T S d o s a g e d u rin g t h e s t u d y

N u m b e r ( n = 21)
%
2 5u g / h r 50u g / h r 75u g / h r
R ed u ced 0 0 0 0
U nchanged 13 4 2 90
In c r e a s e d
50% 0 1 0 5
51- 10 0% 1 0 0 5

(25- 75u g / h r) 21 3 8.7 u g / h r

( 25- 75 u g / h r)
(p> 0.05). 1 24
1
90 m g
. 3
1 2
(p > 0.05) ( F ig u r e. 2).

2)

21
.
(p < 0.01).

3)

F ig u re 2 . M ea n fe n t a n y l d os e(u g / h r), m or ph in e d os e
(m g / d ), a n d m ea n P a in V A S a n d Q O L V A S in 19
( F ig u r e 2). pa t ien ts . D os e of r es cu e m orp h in e n e ed ed w a s u n d er
1 21 20m g / d a y a ft e r em ploy in g T T S - fen ta n y l P a in V A S a n d
Q u a lilit y of life V A S w er e a d eq u a t e t h r ou g h ou t s t u d y
pe r iod .
(p < 0.01).
.
4)
. 3
(T a b le 4). 1 .
7 4 (cold s w eat in g ) (m ild fev er) 5
. 1 . 2 . ( :< 8 / ) 1
24 . . 25u g / h r
90 m g 25 u g / h r 5 (38% ) 75u g / h r
1 3 150 2 (50% ) (p<
m g , 225 m g , 225 m g 3 0.05).
. , , ( p> 0.05).

- 35 3 -
 : 57 3 469 1999

T a b le 4 . S id e e ff e c c t s o f fe n t a n y l- T T S

N u m b e r ( n = 21) %
2 5u g / h r 50u g / h r 75u g / h r T ota l
N a u s ea 5 0 2 7 33
V om it in g 3 0 1 4 20
C o n s t ip a t io n 3 1 0 4 20
C o ld s w e a t in g 5 0 0 5 24
D iz z in e s s 3 0 0 3 14
C o n fu s ion 2 0 1 3 14
fe v e r 2 0 0 2 10
T r em or 0 0 1 1 5
V oid in g d iffic u lt y 0 0 1 1 5
It c h in g 1 0 0 1 5

, , 1 21

(p > 0.05). 1 , 9 , 15, 16)

21
( T ab le 5).

17-19). K or t e 20) 39

30
.
. (V A S < 3.5) 48
24
72
.
7). VAS

(F ig u r e. 2).
. 6, 18, 19) .

T a b le 5 . C o m pa ris io n o f b o d y w e ig h t ( B W t) , b lo o d pre s s u re ( B P ) , H b , W B C , p la te le t , S - G O T a n d S - G P T le v e ls
du rin g s tu d y o f t re a t m e n t p h a s e

day1 day9 d a y 21
BW t 48.9 1.49 49.8 1.98 5 1.3 3.22
D ia s t o lic B P 69.5 1.82 71.4 1.63 7 2.5 2.46
H e m o g lob in 10.7 0.70 10.3 0.72 10.5 0.72
W BC 10600 22.0 11 800 2 4.3 117 00 23 .1
P la t e le t 263000 109.5 212 000 1 03.0 2540 00 10 5.5
S - GOT 42.3 1.39 43.4 1.42 44.7 1.51
S- GPT 31.4 1.19 33.7 1.23 36.4 1.31

- 35 4 -
 7 : -TTS

:
8- 12 1
21), 12 404 m g
2
.
. ,
12
VAS .

. .
: 1996 1 1997 10
(33% ), 22
(24% ), (20% ), (20% ), (14% ), 19 .
(14% ), (10% ), 25 / hr 13 50
, , / hr 4 , 75 / hr 2
(T a b le 4), 1 ,
.
S ou t h a m 16) (33% v s 23% ), 135.3
(20% v s 23% ). B a r b a r a 15) m g (20- 285 m g / d a y )
98 3 20 m g / d a y
24 .
.
24
3 .
.
, 7 , 4
. 1 1

. .
:
,
, .

. .

: .

REFEREN CES
.

1) B ov ill J G : W hich p ot e n t op io id ? I m p o r t an t c r it e r ia
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 K ore a n J ou rn a l of M e dic in e : V ol. 57, N o. 3, 1999

2) M a t h e r LE : C lin ical p har m aco k in e t ic s of fe n tany l an d A m J C lin O n c ol 9( 5) :449- 453, 1986

it s n e w e r d e r iv at iv e s . C lin P har m aco k in e t . 8:422- 426, 13) F oley K M : T he t r e at m e n t of c an ce r p ain . N E n g l J
1983 M e d 318:84- 95, 1985
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