TAP CHI NGHIEN C U U Y HOC •
HIEU QUA DIEU TRj TRUNG DICH TREN BENH NHAN UNG THU' PHOI KHONG TE BAO NHO GIAI DOAN MUON
CO VA KHONG CO DOT BIEN GEN EGFR
Nguydn Minh Ha\ Trin Van Khanh\
Trin Huy Thinh\ o 6 Dinh H^^ Ta Thanh Van^
'Truxyng Dai Hoc Y Ha Noi, ^Tnfong Dai Hoc Y khoa Pham Ngoc Th$ch Lieu phap dieu tn trung dich la mot lieu phap diSu tn moi, da duoc chung mmh co hieu qua cho benh ung thu phdi khong tS bao nho, dac biet tren nhom benh nhan co dot bi4n gen EGFR Nghien cCfu nham danh gia ty ie dap ung toan bo (ORR) voi lieu phap di§u tri tning dich o hai nhom benh nhan ung thw phoi khong t§ bao nho giai doan muon co va khong co dot biin gen EGFR va danh gia thai gian sing b$nh khong Uin tnen (PFS) va thoi gian sdng toan bo (OS) sau lieu phap diiu th triing dich o nhom benh nhan ung thw phoi khong ti bao nho giai doan muon co va khong co dot biin gen EGFR 80 benh nhan ung thu phoi khong ti bao nho giai doan IIIB/IV duoc dieu th dich bang eriotinib Xac dmh dot biin EGFR bang ky thu$t giai trinh tu gen va Scorpions ARMS. Ghi nhan cac dap ung diiu tn sau 03 thang va 06 thang Ghi nh§n va so sanh PFS va OS cua cac nhom benh Kit qua nghien c&u khong ghi nhan dupc trwdng hop nao dap'&ng hoan toan sau 3 thang hoac 6 thang diiu tn dich Co xu huong giam ORR o nhom dot biin EGFR (-) so VOI nhom dot biin EGFR (+). Co sw cai thien co y nghia thing ke a ca PFS va OS o nhom dot biin EGFR (+} Edotinib giiip keo dai sw sing o benh nhan ung thw phdi khong ti bao nho giai do^n muon CO dot bien gen EGFR
TCr khoa: ung thu' phoi khong t4 bao nho; dot bi§n gen EGFR, lieu phap di4u tri trung dich
I. DAT
VANDt
Hien nay, tren toan T h l gidi va tai Viet Nam, ung thu phoi la loai ung tha pho b i l n nhlt v i cd ty le ta vong cao n h l t [ 1 , 2] Mdi lien quan giaa viec hut thudc la v i ung tha phoi da d u o c l i m sang td, n g i y c i n g n h i l u CO che p h i n tu cua qua trinh phat smh, phat tnen ung thu phoi d u a c tim ra [3, 4] 80 - 90%
c i c trudng hpp ung tha phoi la t h l khdng te b i o nhd, cdn lai la t h l te b i o nhd K h i c vdi cac khdl u dae khac, d i n nay, v i n r i t khd phat hien sdm khdi ung t h a phoi, h l u h i t c i c tradng hop khi phat hien da rai vao giai doan
Dia chi lien he Tran Van Khanh, Trung lam Nghien ctm Gen - Protein. Truong Bai hoc Y Ha Noi Email vanktianti73md@yahoo com Ngay nhan 24/12/2013 Ngay fJuQc chap thuan 28/4/2014
tien tnen hoac di can Mac du da cd rat nhieu t i l n bd trong cac phaang thdc dieu tn nhu p h i u thuat, hda tn va xa tri, ty le sdng t o i n the sau 5 nam cua benh nhan ung tha phoi van r l t thap, chl x i p xi 15% [1] Trong nhu'ng n i m g i n day, y hoc da p h i t hien d a a c nhilu dieh phan t d benh hpc t i l m nang trong ung tha phdi, thuc d i y sa ra ddi cua nhdng dup'c p h i m mdl giup dc che hoat ddng cua chung, keo dai thdi gian sdng v i nang cao c h i t laang sdng cua ngadi benh D d l i c h i t dc che hogt tinh tyrosine kinase (TKIs) cua thu t h l y l u to phat t n l n bieu md (EGFR, epidermal growth factor receptor) gdm gefitinib v i eriotinib, d a a c goi l i lieu phap d i l u tn trung dich Nhilu nghien cdu da chdng mmh mdi lien quan chit che gida ddt b i l n gen EGFR vdi mdc dd flip dng thudc cua khdi u trong lieu phap dieu tri trung dich Khoang 10 - 4 0 % benh n h i n ung
TCNCYH 87 (2)-2014
• TAP CHI NGHIEN CUTJ Y HOC tha phoi khdng te b^o nho cd dpt b i l n a exon
1 8 - 2 1 cua gen EGFR. Cac dot b i l n nay ma hda nfin protein EGFR cd ai lyc manh vdi thuoc d i l u tri dich, do dd benh nhan ung tha phoi khdng te b i o nhd mang dot b i l n gen EGFR thadng dap ang tdt vdi thudc d i l u trj dich [5] Tuy nhien, tai Viet Nam chaa cd nhilu nghien cau v l hieu qua cua lieu phap d i l u tri trung dich tr§n b§nh n h i n ung tha phdi khdng te b i p nhd giai doan mudn. Do dd, d l t i i nghien ed'u dup'c thac hien vdi muc tieu:
1. Danh g i i ty le d i p Crng toan bd (ORR) vdl d i l u tn dich d hai nhdm benh nhan ung thu phoi khdng t l bao nhd giai doan mudn cd v i khdng cd ddt b i l n gen EGFR,
2 D i n h g i i thdi gian sdng benh khdng t i l n t n l n (PFS) vS thdi gian sdng toan bd (OS) sau d i l u tri dich a nhdm bdnh n h i n ung tha phoi khdng t l b i o nhd giai doan mupn cd va khdng cd ddt biln gen EGFR.
II. D 6 | TU'gNG VA PHU'aNG PHAP
1. Thiet ke nghien cu'u: t i l n cdu, md ta , logt tradng hpp, cd theo ddi doc thdi gian
song th^m, 2. Ddi tu'O'ng
80 benh nhan ung t h a phoi khdng t l bao nhd giai doan IIIB/IV d a a c d i l u tr; b l n g eriotinib tai bdnh vien Lao v i benh Phdi Trung aang, b§nh vien K Trung aang. benh vien Hau Nghl v i benh vien Bach Mai. Benh n h i n dap-c c h i n d o i n x i c dinh daa vao k i t qua md b^nh hoc v i khdng m i c ung t h a nao khic.
C i c m l u md ung tha phdi due trong parafin, dup'c l i m x6t nghiem tim ddt b i l n gen EGFR tgi trung tam nghien edu Gen Protein, Tradng Dgi hpc Y H i Ndi
3. Phu&ng phdp
Thu th$p c i c thdng tin ve lam sang va can l i m s i n g cua b^nh n h i n tinh trang toan than,
triSu chu'ng lam s i n g , kich thadc u, hach, c i c tdn thaong di can d a a tren kham lam sang, cac xet nghiem can lam sang va hinh anh hpc.
Mdi benh nhan se d a a c theo doi dpc trong sudt thdi gian d i l u trj. b i t d l u t d luc t i l p nhan d\eii tri dich cho d i n khi tiP vong, mat theo ddi hoac ket thuc nghien cdu
Lieu phap d i l u tn trung dich gdm duac c h i t eriotinib 150mg/vien, dimg dadng udng 1 vien/ngay, lien tuc mdi n^ay eho d i n khi benh nhan cd d l u hieu tien tnen benh, xuat hien ddc tinh khdng chap nhan daac, xm ra khdi nghien cdu hoac t d vong
Benh n h i n d a a c chia t h i n h 2 nhdm theo tinh trang ddt b i l n gen EGFR nhdm cd ddt b i l n (EGFR (+)) va nhdm khdng cd ddt b i l n (EGFR (-)) Ddt b i l n gen EGFR daac x i c dmh b l n g ky thuat giai trinh ta gen va k? thuSt Scorpion ARMS vdi dd nhay l l n luot la 30%
[6] va 1 % [7] va dd dac hieu la 100% cho ca 2 ky thuat,
Trong q u i trinh theo ddi d i l u trj, benh n h i n se daac:
Danh gia dap dng toan trang (daa tren nhan dinh cua b i c sy d i l u tri) theo chi sd Karnofsky sau 03 t h i n g , 06 t h i n g (bang 1) Dap dng toan trang d a a c danh gia thanh 2 mdc dn dinh/tang (chi so Karnofsky gia nguyen hoac tang len sau thdi gian d i l u tri) va giam (chi sd Karnofsky giam sau thdi gian d i l u tn)
Danh gia dap dng thac t h l theo tieu chuan RECIST [8] sau 03 v i 06 t h i n g (bang 2) Ty le dap dng toan bd (ORR, Overall Response Rate) d u p c tinh bang tong ciia ty le dap dng hoan toan (CR) va ty le d i p ung mdt p h i n (PR).
Ghl nhan thdi gian sdng benh khdng t i l n tnen (PFS, Progressive-Free Survival) (thing)
TjBkP CHl NGHIEN CIFU Y HOC
b i t d i u ta luc t i l p nhan d i l u tn dich cho d i n khi benh cd d l u hieu t i l n t n l n , benh nhan t a vong vi b i t ky nguyen nhan nao, cd thdng tin cudi cung trong tradng hap m l t theo ddi hoac ket thuc nghien c a u
Ghl nhan thdi gian sdng them toan bd (OS:
Overall Survival) ( t h i n g ) ' b i t d i u t a luc t i l p nhan d i l u trj dich cho d i n khi benh nhan tir vong, cd thdng tin cudi cung trong tradng hap m i t theo ddi hoac k i t thiic nghien cu'u.
Bang 1. Danh gia t o a n t r a n g t h e o c h i s 6 K a r n o f s k y
Diem Mii'c hoat d o n g
100% Khdng cd tneu chirng rd r i n g eua benh, kha nang hoat ddng manh 90% Kha nang hoat ddng binh thadng, theu chifng benh tdi t h i l u
80% Kha nang hoat ddng binh thadng nhang phai cd g i n g Cd mat cua trieu chii'ng benh 70% Khdng cd kha nang hoat ddng binh thadng hoac lam viec nhang cdn t a phuc vu t l i
0% C i n ed s u giiip d d c l n t h i l t va dap'c cham sdc y t l 50% Can cd sa tra giup rat Idn va d a p c cham sdc y te thadng xuyen
40% Khdng t a phuc vy tdi thieu, pan cd sa tra giup lien tuc v i d a a c cham sdc dac biet 30% Liet giudng, n i m vien nhang chaa ed nguy ca t a vong
20% Benh nang cham sdc dac biet d benh vien 10% Hap hdi
0% T d vong
Bang 2. Tieu c h u i n d a n h gia dap upng t h y c t h l (theo RECIST [8])
Tieu c h u i n d a n h gia d a p i r n g t h y c t h l Thong s d danh gia Benh dap
U'ng hoan toan (CR)
Benh dap ii'ng m d t phan (PR)
B e n h n g i r n g t i l n t r i l n (SD)
B e n h tien trien (PD) Dadng kinh Idn
nhit cua khdi u tren CT hoac MRI ngac
Khdl u dich Giam > 30% so b i l n mat _ vdi trade dieu tn
Giam < 30%
hoae tang
< 2 0 %
Tang > 20% so vdl trade d i l u tn Ndng dd e h i t chi
d l l m ung thu (CEA)
Trd ve binh thadng
Khdng tang (nhang chaa t r d v l
ngaong binh thadng) Tiep tue ti Tdn thaang
thif phat
B i l n mat hoan t o i n
Tdn tai dai d i n g nhang khdng x u l t hien them ton t h a a n g mdi
X u i t hien thdm mdt h o i c nhilu tdn thaang mdi
TCNCYH 87 (2) - 2014
— TAP CHI NGHIEN C l f U Y HOC Thdi gian PFS va OS d a a c a d c tinh b l n g cd tong cdng 80 benh nhan tip 04 benh vien phaang phap Kaplan - Meier. S y khac biet v l thda man tidu c h u i n chpn m l u daac nhan thfiri gian PFS v i OS cua cac nhdm se dao'c v i o nghien cau. Oac d i l m cua c i c benh nhan phSn tich b l n g test log rank vdi p < 0,05 dap'c dap'c trinh b i y trong bang 3. Cd 36 benh nhan xem la cd y nghla thong ke. dup'c xac djnh cd dot b i l n gen EGFR trong Oac dire nghien ct>u: Nghi&n ciru t u i n "^^^^ " ^^ ' ^ ^ ^ " ^ " ^ a " ^^^""^ cd dot b i l n gen thu d l y du c i c nguyen t i c dao dac trong "^V ^^^"9 ^)- ^ ^ t"^^' ^^'^"S ^ ' ^ ^ ^ ^ " " 9 '^
nghign ciru y hoc d a a c Hdi ddng dao due ^2,76 ± 12,26. Ty le nd thap han nam a ca 2 trong nghign cifu y smh Tradng Dai hoc Y Ha
Ndi phg duy0t
nhdm cd va khdng cd dot bien EGFR, Khdng hut thudc (hoac da ngang hut thudc > 10 nam) c h i l m ty le eao han d ca 2 nhdm cd le do da
I K £ T Q U A ^° c^c '^^^'^ ^^^" ^^ c^° ^'^^' ^° ^^^'^ ^°^
khdi u eua tat ca benh n h i n deu la dang ung Tii- thing 09/2011 d i n t h i n g 04/2013 da tha b i l u md t u y l n
Bang 3. Dac d i l m lam sang ciia quan t h l nghien CLPU
Dac diem Tu6i (nam)
C h u n g (n = 80) 62,76+ 12,26
Nhom EGFR (+) (n = 36)
Nhom EGFR (-) (n = 44)
G i * i t i n h - n ( % ) Nam NO
45 (56,2%) 35 (43,8%)
19(62,8%) 17(47,2%)
26(59,1%) 18(40,9%) Tifin SLP liut t i i u d c - n (%)
Hut
Khong hut {ho$c da ngu-ng > 10 nSm)
25(31,3%) 55 (68,7%)
8 (22,2%.) 28 (77,8%)
17(38,6%) 27(61,4%)
Typ mo benh hpc - n (%) Carcinom tuyen Carcinom vay Carcinom te bao ldn
80(100%,) 0 0
36(100%.) 0 0
44(100%) 0 0
Ty 1$ dot b i l n gen EGFR trong q u i n the nghien cdu l i 45% (36/80), trong dd chu y l u la ddt biln LREA (dOt b i l n xda dogn d i l n hinh khdng l i m lech khung dich ma) d exon 19 (chilm 55,6%) v i dot b i l n d i l m L858R a exon 21 ( c h i l m 38,9%) N g o i i ra cdn phat hien mdt sd dot b i l n cd nghTa k h i c vdi ty 1$ t h i p han nha dot b i l n d i l m G719S d exon 18 (2,8%) va ddt b i l n xda doan khdng d i l n hinh d exon 19 (2,8%) Khdng phat hien tradng hop nao mang ddt b i l n gay khing TKIs (bang 4)
TAP CHI NGHIEN CU'U Y HOC •
Bang 4. K i t qua xac djnh dot b i l n gen EGFR
Tinh trang dot b i i n Got biSn EGFR (-)
e a t bi§n EGFR (+) Dot biSn LREA Bot b i j n L858R B 6 t b i 6 n G 7 1 9 S
Bot b i i n xoa doan khong dien hinh
Exon dot bign
19 21 18 . 19
S 6 lipang: ngipcpj (%) 44/80 (65%)- 36/80 (45%,) 20/36 (55,6%,) 14/36(38,9%,) 1/36 (2,8%,) 1/36(2,8%)
Ddi vdl dap irng thac the, nghien ci^u khdng ghi nhan d a a c tradng hap nao dap ang hoan toan sau 3 t h i n g hoac 6 t h i n g d i l u trj dich Cd xu hadng giam ty le d i p irng toan bd ORR a nhdm dot b i l n EGFR (-) so vdi nhdm ddt b i l n EGFR (+) ORR sau 03 t h i n g va 06 t h i n g d nhdm ddt b i l n EGFR (+) lan luot la 33,33% v i 20% so vdi nhdm ddt b i l n EGFR (-) la 25% va 5% (bang 5). Tuy nhien, su chdnh lech n i y khdng ed y nghTa thdng ke
d ca 2 thdi diem sau dieu tn neu tren (3 thing:
R R = 1,33; 95%CI 0,61 - 2,12 va 6 t h i n g : RR
= 4, 95%CI: -1,49 - 14,73) Ben canh do, ghi n h i n cac dap ipng toan trang cua benh nhan cho t h l y chl sd Karnofsky on dinh/tang sau 03 thang va 06 thang d i l u tri d nhdm dot biln EGFR (+) l l n laot la 69,44% va 80% so vdi nhdm dot b i l n EGFR (-) la 52,27% va 40%, cho t h l y c h i l u hadng cai thien t o i n trang va ca nang tdt han a nhdm cd dot b i l n EGFR (+)
Bang 5. Ty le cac dap li-ng thyc t h l (theo RECIST)
Loai dap U'ng CR PR
Sau 03 thang EGFR (+) (n = 36) EGFR (-) (n = 44)
0 0 12/36 (33,33%o) 11/44 (25%o)
Sau 06 thang EGFR (<•) (n = 20) EGFR (-) (n = 20)
0 0 04/20 (20%) 01/20 (6%) 16/36(41,67%) 14/44(31,82%) 14/20 (70%) 14/20 (70%)
09/36 (25%) 19/44(43,18%) 02/20(10%) 05/20(25%) ORR = CR + PR 12/36(33,33%,) 11/44(25%,) 4/20 (20%) 1/20 (6%)
RR = 1,33, 95%,CI 0 , 6 1 - 2 , 1 2 RR = 4, 9 6 % C I : - 1 , . - 14,73
(CR dap ling hoan toan; PR- dap irng mot p h i n ; SD benh on dinh, PD: benh t i i n trien, ORR:
dap LKng toan bo)
TCNCYH 87 (2) - 2014
• TAP CHI NGHIEN CUU Y HOC Bang 6. Ty le cdc dap u>ng toan trang (theo c h i s d Karnofsky)
Loai dap U'ng On dinh/tang Giam
Sau 3 thang EGFR(+)(n = 36) EGFR (-) (n = 44)
26/36 (69,44%,) 23/44 (52,27%) 11/36 (30,56%,) 21/44 (47,23%)
Sau 6 thang EGFR (+) (n = 20) EGFR (-) (n = 20)
16/20(80%)^ 08/20(40%,) 04/20(20%) 12/20(60%,)
Ddi vdi thdi gian sdng them, cd sa cai thien cd y nghTa thdng ke d ca PFS va OS a nhdm dot bien EGFR (+) Trung vi PFS d nhdm dot b i l n EGFR (+) so vdi nhdm dot b i l n EGFR (-) lan laat la 7,5 t h i n g va 4,25 t h i n g (p = 0,015). Taang ta, trung vi OS a nhdm ddt bien EGFR (+) so vdi nhdm dot b i l n EGFR (-) l l n laat la 13 t h i n g v i 8 t h i n g (p = 0,041) (bang 7}
Bang 7. Thd'i gian s d n g PFS va OS o- 2 n h o m benh nhan
Trung vj PFS (thing)
(n = 80) OS (thang)
(n = 80)
Nhom EGFR (+) 7,5
13
Nhom EGFR (-) 4,26
8
HR = 2,21 (95%Ci = 1 , 1 7 - 4 , 1 8 ) ; p = 0 , 0 1 5 H R = 1,63(95%Ci = 1,06-2,76);
p = 0,041
•V
- - ^ E G F R ( )
B i l u d d 1. Bieu d d Kaplan - Meier t h l hien thd'i gian s d n g t h e m toan bd (OS) va thd'i gtan s d n g benh k h d n g t i l n t r i l n (PFS) cua 2 n h d m benh nhan cd va khdng cd
d o t b i l n gen EGFR
TAP CHI NGHIEN CLTU Y HOC •
IV. BAN LUAN
Tren 70% tradng hpp ung t h a phoi khdng t l bao nhd khi d a c e phat hien da d giai doan t i l n xa (IIIB/IV), ngadi benh khdng cdn kha nang p h i u thuit, cdn lieu p h i p hda tri co d i l n k i t hap hai thudc (platinum va doeetaxel) da dat d i n "tran" cua hieu qua d i l u tn vdi ty le sdng 1 nam la 33% va 2 nam la 1 1 % [9].
Trong bdi canh dd, eriotinib va gefitinib da cho t h l y hieu qua v a a t trdi so vdi hda c h i t t r u y i n thong dac biet tren nhdm benh nhan cd dot b i l n gen EGFR Hieu qua nay da d a a c chdng mmh qua n h i l u phan tich hdi ciru va thif nghiem lam sang [10, 11] Nghien ciru nay theo ddi 80 benh n h i n ung t h a p h d i khdng t l b i o nhd giai doan mudn tai Viet Nam d a a c d i l u tn dich b i n g eriotinib, trong dd cd 36 benh nhan cd ddt b i l n EGFR nhay cam vdi TKIs, cho cac k i t qua phii hap vdi cac bao cao trade trdn t h l gidi
Dap irng cua ngadi benh ddi vdi lieu phap d i l u tn trung dich d u a c theo ddi trong 6 t h i n g , gdm dap irng thac t h l (theo RECIST) va d i p Lcng toan trang (theo chi sd Karnofski). Nghien ciru ghl nhan d u a c xu haang giam ty le dap Lfng toan bd ORR d nhdm ddt bien EGFR (-) so vdl nhdm dot b i l n EGFR (+) ORR sau 03 thing v i 06 t h i n g a nhdm ddt b i l n EGFR (+) l i n laat la 33,33% va 20% so vdi nhdm ddt b i l n EGFR (-) la 25% va 5% Tuy nhien, sa chenh lech nay khdng cd y nghTa thdng ke cd t h l do benh da vao giai doan cudi, kich thadc khdl u da ldn va cho di can nen ty le d i p irng hoan toan v i mdt p h l n khdng cao va khdng vaat trdi rd ret d nhdm cd ddt b i l n (bang 5) Khi xet dap irng toan trang, ty le on dinh/tang chi sd Karnofski d nhdm ddt b i l n EGFR (+) d l u eao han nhdm khdng dot b i l n a ca thdi d l l m 3 t h i n g va 6 t h i n g (ty le l l n laat la 69,44% va 80% so vdi 52,27% va 40%) cho thay nhdm benh ' n h i n cd dot b i l n d a o c
hadng Ip'i tir s a cai thien toan trang n h i l u han nhdm khong dot b i l n
0 6 i vdi thdi gian sdng them, cd s a cai thien cd y nghTa thong ke a ca PFS va OS d nhdm ddt b i l n EGFR (+). Trung vj PFS a nhdm dot b i l n EGFR (+) so vd'i nhdm ddt biln EGFR (-) l l n luat la 7,5 t h i n g va 4,25 thing (p = 0,015); trung vi OS a nhdm dot biln EGFR (+) so vdl nhdm ddt b i l n EGFR (-) lin laat la 13 t h i n g va 8 t h i n g (p - 0,041). Kit qua nay cho t h l y s a hien dien cua ddt biln gen EGFR giup keo dai thdi gian sdng cho nhdm benh nhan diing lieu p h i p d i l u tn triing dich, hoan toan phii hap vdi k i t qua eua thi>
nghiem GALGB [12] Tuy nhien, trung vi PFS va OS trong nghien ciru d l u n g l n han trong thCr nghiem CALBG ( l l n laat la 7,5 thang va 13 t h i n g so vdi 14,1 t h i n g va 31,3 thing), diJ tieu c h u i n chon m l u d l u l i ung tha phoi khdng te b i o nho giai doan IIIB/IV, Nguyen nhan cd le do nghien c d u chaa p h i n dmh lieu p h i p d i l u tri triing dich bade 1 hoac budc 2, trong khi thCr nghiem CALBG chi chon phic dfl eriotinib b a d e 1 tren benh n h i n khdng hut thudc la, vdn la ddi t a a n g nhay cam vdi lieu phap d i l u tn triing dich han Day l i v l n de chaa giai q u y l t 6\fac cua nghien ciru. so sanh hieu qua lieu phap d i l u tn triing dich bade 1 hoac bade 2 tren hai nhdm benh nhan ung tha phoi khdng t l b i o nhd giat doan cuoi cd va khdng cd ddt b i l n gen EGFR. Tuy nhien, do thuc t l .dilu tri ung tha ndi chung va ung tha phoi khdng t l bao nhd ndi heng tai Viet Nam cdn nhieu tranh cai, n h l t l i dirng trade mdt lieu p h i p d i l u tn triing dich mang lai hieu qua nhang cdn m d i me, mdt bd phan benh nhan v l n phai chiu ganh nang kinh le khi theo duoi lieu phap d i l u tri nay, nen viec lua chon benh nhan cho cac nghien ciru danh gici lieu phap d i l u tn triing dich cdn r l t khd khin.
Trong taang lai g i n , khi lieu p h i p d i l u tri
TCNCYH 87 (2)-2014
• TAP CHI NGHIEN CUU Y HOC trung dich cho ung t h a phoi khong t l bao nho
ph6 bien han nO'a tai Viet Nam, nghien ciru ed the p h i t tnen de giai quyet van de tren vdi sd laang m l u Idn han, de cho cac k i t qua cd y nghTa han v l mat t h i n g ke va daa ra dap'c c i c k i t l u i n chinh xac cho tirng nhdm benh nhan ung tha phoi khdng t l bao nho (ddt b i l n / khdng ddt bien EGFR, hut thuoc/khdng hiit thuoc, giai doan sdm/mudn, d i l u tn dich budc 1/bade 2. )
V. K^T LUAN
Tuy chua xae djnh d a a c sa eai thien ty le d i p irng toan bp sau 3 va 6 t h i n g d i l u tr;
nhang d i l u tr; dieh b i n g eriotinib da keo d i i daac thdi gian sdng benh khdng t i l n t r i l n va thdi gian sdng them toan bd a nhdm benh nhan ung tha phoi khdng t l b i o nhd giai doan mudn cd ddt b i l n gen EGFR,
Lo'i c a m O T I
NghiSn ciru daac hd tra kmh phi bdi D l tai cap n h i nudc "Nghien ciru x i c dinh ddt b i l n gen quylt dinh tinh d i p irng thudc trong d i l u tn ung thu dai trac t r i n g v i ung tha phdi"
Nhdm nghien ciru t r i n trong cam an sa giiip dd cua c i c can bd v i ddng nghiep tai Trung t i m Nghiin eiru Gen - Protein v i bd mdn Hda sinh - Trudng Dai hoc Y Ha Nor cung nha cac b i c sy tgi khoa Ung badu benh vien Hdu Nghl, Bach Mai, K Trung aang v i benh vien Lao phoi Trung aang.
TAI LIEU THAM KHAO
1. Jemal A, Bray F, Ward E et al (2011).
Global cancer statistics, CA Cancer J Clin. 61 (2), 69 - 90,
2. Chu Hdng ThSng. Le T r i n Ngoan, Le Hoai Chu-ffng, Vu Thj Nguyet A n h (2013).
Tinh hinh ta vong do ung tha tai Ha Ndi va T h i l Nguy6n, 2005 - 2008 Tap chi Thong Tin Y Dupc. 4. 5 0 - 5 4
3. Sato M, Shames DS, Gazdar AF, Minna JD (2007). A translational view of the molecular pathogenesis of lung cancer. J Thorac Oncol, 2, 327 - 343.
4. Wistuba li, Mao L, Gazdar AF (2002).
Smoking molecular damage in bronchial epithelium. Oncogene, 2 1 , 7298 - 7306
5. Pao W, Miller VA (2005). Epidermal grovrth factor receptor mutations, small- molecule kinase inhibitors, and non-small-cell lung cancer: current knowledge and future directions J Clin Oncol, 23(11), 2556 - 2568
6. Danphe W.B. and Daniel A.H (2006). A Blood-Based Test for Epidermal Grovrth Fac- tor Receptor Mutations in Lung Cancer, Clin Cancer Res , 12, 3875 - 3877
7. EGFR PCR Kit Handbook (2010).
www qiagen com
8. Therasse P., A r b u c k S.G. et al (2000).
New guidelines to evaluate the response to treatment in solid tumors European Organiza- tion for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada J Natl Cancer Inst, 92, 2 0 5 - 2 1 6
3. Schiller J H , Harrington D, Belani CP, ef al (2002). Comparison of four chemother- apy regimens for advanced non-small-cell lung cancer N Engl J Med, 346, 92 - 98
10. Mok T.S., Wu Y.L., Thongprasert S.
et al (2009). Gefitinib or Carboplatin-Paclitaxei in Pulmonary Adenocarcinoma N Eng J Med, 361(10), 9 4 7 - 9 5 8
11. Mitsudomi T, Morita S, Yatebe Y, et ai (2010). Gefitinib versus cisplatin plus doeetaxel in patients with non-small cell lung cancer harbouring mutations of the epidermal growth factor receptor {WJTOG3405) An open label, randomized phase 3 trial Lancet Oncol. 1 1 , 121 - 128
TAP CHI NGHIEN CU'U Y HOC -
12. Janne P.A., W a n g X. et al (2012). were never or light former smokers witf Randomized Phase II Tnal of Eriotinib alone or advanced lung adenocarcinoma CALBG with Carboplatin and Paclitaxel in patients who 30406 Tnal. J Clin Oncol, 30, 1 - 9 .
Summary
EFFECT OF TARGETED THERAPY IN ADVANCED NON-SMALL CELL LUNG CANCER PATIENTS HARBORING EGFR MUTATIONS
Targeted therapy is an effective method for treatment of non-small cell lung cancer (NSCLC) However, the response was demonstrated only in EGFR-mutated NSCLC patients, Objectivesof the study were to assess the overall response rate (ORR) for the targeted therapy in EGFR - mutated and non EGFR - mutated advanced NSCLC patients, (2) Comparing the progressive-free survival (PFS) and the overait survival (OS) after the targeted therapy of these two groups of patients 80 gefitinib or eriotinib - treated stage MIB/IV NSCLC patients were selected for this study; Identify mutation by sequencing and Scorpions ARMS techniques; Observe the response of the targeted treatment after 3 and 6 months, compare the PFS and OS of the subgroups, no complete response was observed after 3 and 6 months of targeted treatment ORR tends to decrease in non EGFR - mutated group compared with EGFR - mutated group There was a statistically significant improvement in both PFS and OS of EGFR - mutated group, Gefitinib or eriotinib can prolong the survival of the srdvanced NSCLC patients harbonng EGFR mutations Keywords: non small cell lung cancer; EGFR m u t a t i o n ; targeted t h e r a p y
TCNCYH 87 (2) 2014
