TAP CHi Y HOC VIET NAM TAP 459 • THANG 10 - SO 2 - 2017 trang nhiem rubella d phu nit mang thai ed nguy
cd va hgi chu'ng rubella bam sinh tai Benh vien Phu san Trung udng, luan an tien sT y hgc, Tru'dng Dai hoc Y Ha Npi
4. Onakewhor JU, Chiwuzie 3 (2011).
Seroprevalanee survey of rubella infection in pregnancy at the University of Benin Teaching
Hospital, Benin City, Nigeria. Niger J Clin Pract , 2011Apr-3un;14(2): 140-5,
. Phan Thanh Hai (200S). Nghien ciili mptsdlydo,^
danh gia hieu qua cua Misoprostol trong pha thai tu 17 den 22 tuan tai Benh vien Phu San Thing ddng nam 2008, luan van tot nghiep bac sT chuyen khoa cap II, Tru'dng Dai hpc Y Ha Ngi, 57-58.
DANH GIA KET QUA DIEU TRI BO TRQ* UNG THU* VU GIAI DOAN IMIIA BANG P H A C Dib 4AC - 4D
TOM TAT
Myc tieu: Oanh gia ket qua dieu tri bo try va mot so doc tinh ciia phac do 4AC - 4D d benh nhan ung thiT vii glai doan ITIIIA. Doi lu'Ong va phu'dng phap nghien cuti: Nghien cii^j mo ta hoi CLTU C6 theo doi doc ^32 benh nhan ung thy vii giai doan IHIIA duUc phlu thuat triet can va dieu tri bo trd bang phae ilo4AC - 4D tei Beiih vien K t y thang 01/2013 den thang 08/2017. Ket qua: Tuoi mac benh trung binh la 47,5 ± 7,6, hay ^Sp nhat 40 - 49 chi^m 53,1%. Vi tri u vii 'A tren ngoai la 71,9%. UTBM tlie ong xam nhap (84,4%), do mo hoc 2 chiem chii yeu (71,9%). ER, PR, HER2 dUOng tinh tyong img la: 53,1%; 50%;
56,2%. Giai doan benh IIA, IIB, IIIA la: 43,8%; 25%;
31,3%. Ty le song them khong benh va song them toan bo 1, 2, 3 nam la: 100%; 91,4%; 86,9% va 100%; 95,5%; 95,5%. Doc tinh tren he huyet hoc la ha bach cau trung tinh do 1, 2 (43,8%), ha do 3 (12,5%), do 4 (6,2%); giarh huyet sac to chii yeu do 1 (71,9%), do 2 (3,1%), khong co dp 3, 4. Khong gap ha tieu cau va suy than. Tang men gan dp 1 la 31,2%, do 2 la 15,6%, tang men gan do 3 (3,1%), khong cd ta'ng men gan do 4. Ket luan: Phac do 4AC - 4D trong dieu tri bo trd UTV giai doan IHIIA mang lai ty le song them cao va dgc tinh chap nhan du'dc.
T^ khoa: ung thd vii giai doan II-IIIA, phac do 4AC-4D.
SUMMARY
EFFICACY AND TOXICITY OF ADJUVANT 4AC-4D I N PATIENTS W I T H STAGE I I - I I I A
BREAST CANCER
Purpose: Toacssess adjuvant result and toxicity of 4AC-4D regimen in patients with stage II-IIIA breast cancer. Patients and methods: 32 patients with stage II-IIIA postoperativebreast cancer treated byadjuvant 4AC - 4D regimen at National Cancer Hospital. Results: Theaverage age was47,5 ± 7,6 years; the most commonage wasfrom 40 to 49 years
^Binh vi$n Ung Bddu Nghe An
^Bd mon Ung thd Trddng Dai hpc y Ha Noi Chju b^ch nhiem ehinh: Le Thi Sydng Email: [email protected] Ngay nhan bai: 12.8.2017 Ngay phan bien khoa hpc: 29.9.2017 Ngay duyet bai: 6.10.2017
Le Thi Suong', Le Van Quang^
old (53,1%). The most common location of breast tumor was uoper outsidequarter (71,9%). The invasive ductal carcinoma was most common (84,4%), mainly grade 2 (71,9%). Disease free survival rate and overall survivalrate at 1, 2 and 3 years follow-up were 100%; 91,4%; 85,9% and 100%; 95,5%; 95,5%, respectively. Most common side effects afterS cycles were qrade 1 or 2, rarelv arade 3 or 4toxicities. Grade 1, 2 of hematoloqic toxicitv included: neutropenia (43,8%), anemia (75%), andnoneuphrotoxic and thrombocytopenia were observed.Grade 3 of neutropenia (12,5%). qrade 4 (6,2%).Grade 1 heoatotoxicitv was seen m 31.2%. qrade 2 (15,6%) and qrade 3 (3,1%), but no grade 4 hepatotoxicity was observed. Conclusion: 4AC-4Dregimenresults a high survival rate in the setting of postoperative patients with stagell-IIIA breast cancer, with an acceptable overall toxicity profile.
Keywords: Stage II-IIIAbreast cancer, 4AC - 'ID regimen.
I. OAT VAN OE
Ung t h y vii (UTV) la loai ung thy pho bien nhat d phu nff nhieu nyde tren the gidi. Theo hiep hpi ung thy My yde tinh co khoang 234.190 ngydi My dydc chan doan UTV xam nhap va khoang 40.730 chet vi benh tai My trong nam 2015. Tai Viet Nam, UTV ciing dirng hang dau trong cac loai ung t h y cita phu nu". Theo ghi nhan ung t h y tai Ha Npi giai doan 2001-2004 ty le mac UTV ehuan theo tuoi la 29,7/100.000 dan va d thanh phd Ho Chi Minh ty le nay la 19,1/100.000 dan.
Mac dii CO khoang hdn 90% UTV dydc phat hien d giai doan sdm con kha nang phau thuat dydc nhyng nghien ciru cung da ehi ra rang ed hdn 50% chet vi benh neu chi phau thuat ddn thuan trong 30 nam theo ddi. Vi vay dieu trj bo trd sau phau thuat dydc ehi dinh eho giai doan nay nham muc dich tieu diet nhutig vi di can giiip cai thien thdi gian song them khong benh va thdi gian song them toan bp. Oieu tri bo trd cho UTV giai doan sdm bao gom hoa chat va lieu phap npi tiet, dieu trj dich Her-2, xa tri khi co chi djnh. Tir nam 1976 den nay da co rat nhieu thif
VIETNAM MEDICAL JOURHAL W°2 - OCTOBER - 2017 nghiem lam sang va eac nghien^ciTu Idn khang
dinh dydc vai tro ciia hoa chat bo trd trong dieu tri UTV. Tir nhii'ng nghien cu'u dd cac thuoc Anthraeylin, Cyclophosphamid, Taxan da trd thanh nen tang cho dieu trj bo trd UTV giai doan sdm.Trong thir nghiem lam sang ECOG-E1199 da chi ro ldi ich ve eai thien song them khong benh (DPS) 5 nam d nhdm benh nhan dydc dieu trj 4AC-4Docetaxel 3 tuan la 81,2% hoac 4AC- 12Paclitaxel hang tuan la 81,5%, cdn d nhdm dydc dieu tri bang 4AC-4Paclitaxel 3 tuan thi DPS 5 nam la 76,9%. Tai Viet Nam da co rat nhieu cong trinh nghien ciiu ve dieu trj bo trd trong UTV giai doan sdm nhyng chya co nghien eifu nao ve bo trd bang phae do 4AC-4Docetaxel.
Vi vay, chiing toi tien hanh nghien ciTu de tai nay vdi muc tieu-.Danh gia Iretqua dieu tri va mot so doc tfnh cua phac do bd trd 4A C-'fD tren binh nhin UTV giai doan II-IIIA.
II. OOI TU'ONG VA PHUCnsiG PHAP NGHIEN CCTU 2.1. Ddi tu'dng nghien cu'u: Bao gom eac benh nhan UTV giai doan I I - IIIA da dydc phau thuat triet can, dieu trj hoa chat bo trd phac do 4AC- 4Docetaxel tai benh vien K tir thang 1/2013 den thang 8/2017.
Tieu ehuan Ida chon
-Benh nhan nu' ddric chan doan UTBM vu xam lan giai doan I I - IIIA.
-Oudc dieu tri hoa chat bo trd sau phau thuat bang phac do 4AC - 4D, sau dd dieu tri npi tiet, xa trj khi co ehi dinh.
-khong mac ung t h y khac ngoai UTV.
-Cd ho sd lyu trii'day dii.
-Cd thong tin sau dieu trj.
Tiiu ehuan loai trif:
-Khong dii eac tieu chuan tren.
2.2. Phu'dng phap nghien cu'u: Phydng phap nghien eifu md ta hoi ciru32 benh nhan LTTV giai doan I I - IIIA da dydc phau thuat triet can, dieu trj hoa chat bo trd phac do 4AC-4 Docetaxei tai benh vien K tir thang 1/2013 den thang 8/2017.
Phu'dng phap thu thap sd lieu: Thu thap so lieu theo mau bSnh an nghien ciru.
1,^2.3. Phan tich va xCt ly so lieu: Thu thap
%\Y.d ly sd lieu bang phan mem SPSS 16.0.
III. KET QUA NGHIEN CLTU VA BAN LUAN 3.1. Dac diem nhom benh nhan nghien eifu
Tudr. Nhdm tuoi 40-49 hay gap trong nghien eiru eiia ehiing tdi la 17/32 (53,i%), tuoi trung binh mac benh: 47,6 ± 7,6. Ket qua phu hdp vft Tran Hiep, do tuoi 41-50 chiem 51,16%'. Phii hdp vdi Nguyin Dieu Linh, do tuoi 41-50 chiem 47,5%. So sanh vdi cac tac gia phydng Tay thi dp tuoi trung binh mac UTV trong cac nghien cdu la 50; 51 tuoi. Day la mot yeu to khac biet kha quan trong chifng td do tuoi mac UTV tai Vilt Nam CO xu hydng tre lidn cac nddc Phydng Tiy tif do de cac nha dich t l hoc cting nhy bac si'lam sang cd chien lydc chii y phat hien sdm hdn tinh trang benh nhan UTV tre tuoi tai Viet Nam.
Vi tri u. Trong nghien cu'u eiia chung t6i, ty le gap UTV trai la 17/32 (53,1%), cao hdn so vcfi UTV phai. Hay gap nhat la UTV V4 tren ngoai chiem 23/32 (71,9%). Ket qua eua ehiing toi cung phii hdp vdi nghien eifu eiia Tran Hiep, UTV trai chiem 5 4 , 1 % ; u V* tren ngoai chiem 56,32%, eQng nhy nghien ciru ciia Nguyen Dieu Linh vi tri u vii trai ehiem 58,1%. Le Hong Quang Cling ghi nhan ty le UTV trai ehiem gan 55% va u VA tren ngoai ehiem 6 2 , 1 % .
Md binh hgc
- Loai mo benh hpc: Loai mo benh hoc UTV hay gap nhat chimg toi ghi nhan dydc la th§'ong XN chiem 27/32 (84,4%), the tieu thiiy XN chieni 1/32 (3,1%), the tiiy ehiem 1/32 (3,1%).
Ket qua eiia chung toi phii hdp vdi Ta Van Tc(
UTV the 6ng_ xam nhap ehiem ty le eao nhat 79%, the tieu thiiy cliiem 2,9%; phii hdp vdi Tran Hiep the ong xam nhap ehiem 93,76%. Ket qua eiia ehiing toi eung phii hdpy van loai mo benh hpc hay gap nhat trong UTV van la UTBI>1 the dng xam nhap kinh dien ehiem khoang 75%.
- Dp mo benh hpc: 27 benh nhan trang nghien eifu ciia chiing toi xac dinh dydc do mo hpc, t / le dp 2 eao nhat 23/32 (71,9%). 06 mS benh hoc trong UTV cung la yeu to cjuan^rpng giiip tien lydng va gdp phan hydng dan dieu tri bo trd. Op mo hpc cang cao thi dp ac tinh cang cao, tien lydng cang xau. Ket qua nay phu hdp vdi nghien eiru eiia Ta Van Td UTV the ong xam nhap do mo hpc 2 chiem ty le cao 71,4%, dp 1 chiem 12,5%, do 3 chiem 16,4%.
Hda md mien dich ,,^^.Bang 3.1. Hda
\ Thu t h e hoc 16 tren u
ER PR HER2
mo mien dich Dirtfn n 17 16 18
g tinh
»/o 53,1
50 56,2
Am tinh 15 16 14
46,9
%
50 43,8
Tonq n 32 32 32
»/o 100 100 100
TAP CHi Y HOC VlgT NAM TAP 459 - THANG 10 - s 6 2 • 2017 Ty le boe 16 ER tren mo u ciia chung toi la
17/32 chiem 5 3 , 1 % . Ty le boe Ip PR la 15/32 (50%). Ty le boe 16 HER2 tren m6 u cao chiem 56,2% (trong dd Her2 2-i- la 15,6%; Her2 3+ la 40,6%). Ket qua nay phii hdp vdi Nguyen Phue Duy Quang ty le ER, PR dydng tinh lan lydt la 53,3%; 46,7%; phii hdp vdi Ta Van Td ty le ER, PR dydng tinh lan lydt la 5 9 , 1 % ; 51,4%; HER2 3+ chiem 3 5 , 1 % . Ty le bpc 16 ER cita ehiing toi tydng dydng so vdi cac tac gia nhy Malaysia,
Singapore, Thai Lan dao ddng tir 53,8% den 65%. Tuy nhien so vdi cae tac gia Phydng Tay b/
le bpc Ip ER, PR eao hdn han. Theo Sparano J A thi t / le bdc lo ER va hoac PR la 7 0 , 1 % ; cting nhy nghien ciru Sandra M. Swain, MD thi ty le bpc Ip ER la 75%, HER2 3+ la 18,9%. Oieu nay chu'ng to khong cd sy tydng dong hoan toan ve ban chat sinh hpc benh UTV giii'a dan cy Chau A so vdi dan cyCliau Au.
Phan loai giai doan benh Bang 3.2. Phan ioai giai doan benh
Giai doan benh Phan Ioai tiieo nhom giai
doan
IIA IIB IIIA Tonq
So benh nhan 14
8 10 32
TV ie »/o 43,8
25 31,2
100 Bang 3.2 chi ra; glai doan IIA chiem ty le eao
hdn vdi 14/32 (43,8%). Giai doan IIB ehiem 25%, n i A ehiem 31,2%.Theo Tran Hiep thi giai doan IIA ehiem 24,96%; giai doan IIB (54,24%).
sy khac biet nay la do nghien ciru cita Tran Hiep chi ghi nhan d nhdm benh nhan tijr giai doan I-UB.
3.2. Thdi gian song t h e m Thdlgian song them khdng benh
Bieu ^3.1. Ty le song them khdng benh Tat ca 32 benh'nhan ciia chung toi deu dydc theo doi ^ y dii, khong benh nhan nao bi mat thong tin theo doi. Ket qua: t / le song them khong benh tai thdi diem 1 nam, 2 nam, 3 nam tydng ifng la 100%; 91,4%; 86,9% (trong do ed 1 b|nh nhan di can nao vao thang thif 16, 1 benli nhan di can xydng vao thang thir 23 va 1
\knh nhan di can gan vao thang thir 33).
' So vdi Tran Van Thuan b/ ie song them khong benh 1 nam, 2 nam, 3 nam, 4 nam tydng irng la: 97,53%; 88,38%; 80,05%; 75,51%; ket qua ciia Chung toi cao hdn. Dieu nay ciing de ly giai vi nghien cu'u cua Tran Van Thuan ehi bo trd bang 4 ddt AC. Cae nghien eiru tren the gidi da ehi ra rang khi them Taxan tuan t y sau 4 ddt AC trong dieu trj bo t r d UTV thi ty le song therri khong benh ciii thien cd y nghia thong ke so vdi
bo trd 4AC ddn thuan. Cung nhy theo ket qua nghien cinj song them ciia tac gia Nguyen Dieu Linh thi ty le song them ciia nhdm dydc dieu trj bo trd bang phac do 4AC tai thdi diem 1 nam,2 nam, 3 nam, 4 nam lan lydt la 100%; 96,7%;
93,5%; 90,3%; nhom benh nhan bo trd bang TAC thi ty le song them 1 nam, 2 nam, 3 nam, 4 nam tydng u'ng la 98,4%, 95,%, 88,9%; 74,6%.
Nghien eiru eiia ehiing toi eung cd ket qua cao hdn so vdi nghien ciTu eiia tac gia Do Thj Kim Anh vdi ty le sdng them khong benh 1 nam, 2 nam, 3 nam, 4 nam tydng irng la 90,6%;
7 9 , 1 % ; 77%; 73%.
Ket qua song them khong benh cita chiing tdi so vdi nghien eiru ECOG 1199 la tydng dydng. Nghien eiru ECOG 1199 la mot nghien eiru vdi c9 mau ldn 4950 benh nhan UTV sau phau thuat chia deu ngau nhien thanh 4 nhom nhan bo i:rd bang eac phae do 4AC-4D; 4AC-4P;
4AC-Doeetaxel tuan; 4AC- Paelitaxel tuan. Mijc tieu ehinh eiia nghien ciru la thdi gian song them khong benh. Ket qua ciia nghien ciTu nay khi so sanh vdi nhii'ng benh nhan nhan dieu trj ehuan bang phac do 4AC-4 Paelitaxel moi 3 tuan thi HR=1,23 d nhdm nhan bo trd bang 4AC-4D moi 3 tuan (p=0,02) Nghien ciru nay tiep tue dydc theo doi vdi thdi gian theo doi trung vj 12,1 nam thi sdng them khong benh van cai thien cd y nghTa thong ke d nhom dieu tri bo' trd phae do 4AC-4D so vdi nhom dieu tri bo trd 4AC-4P moi 3 tuan. Cijng chinh dya tren ket qua ciia nghien eifu nay ma hien tai hydng dan thyc hanh eiia NCCN cho UTV da chuyen phae do 4AC- 4Paelitaxel moi 3 tuan ra khoi danh sach cae phac do bo trd cho UTV. Tuy thdi gian theo dol song them trong nghien cii'u ciia chiing tdi chya dai nhyng ket qua ciia ehiing toi nhy vay la rat kha quan.
VIETNAI^ MEDICAL JOURNAL N°2 • OCTOBER - 2017 Thdlgian sdng them toin bd
Bieu dd 3.2. Ty IS sdng thim toan bd
Nghien ciiu cita chung toi vdi thdi gian theo doi song them toan bp eon ngan, trong thdi gian theo doi chung toi chi ghi nhan dyde mottruSng hdp benh nhan tir vong vao thang thdXJ do d[
can nao. Ty le song them toan bo tai thdi diem 1 nam, 2 nam, 3 nam lan lydt la 100%; 95,5%' 95,5%. Trong nghien cu'u ECOG 1199 thi ty |g song them toan bo 5 nam khi dieu trj fao trd bang phae do 4AC-4D la 87,3% tuy nhien cai thien khong co y nghla thong ke so vdi phae do bo trd 4AC-4Paclitaxel moi 3 tuan [4]. Do vay chiing tdi chi xin ghi nhan ket qua ve thdi gian song them toan bp ehif khong ban luan nhieu.
3.3. Mot SO dpc tinh cua phac do Ddc tinh tren huyet hgc, gan than Bang 3.3. 06c tinh tren huyet hoc, gan than
fioc tinh tren huyet hoc, gan.
than BC tonq
BCTT Hb SCOT SGPT Sot giam BC
tio aoctinn ( n = j , ^ ) n ( % )
eso
15 (46,9) 12 (37,5) 8(25) 17 (53,1)
16 (50) S o l n C/o) 12 (37,5)
7 (21,9) 23 (71,9) 14 (43,1) 10 (31,2)
Do 2 n («/o) 4(12,5) 7 (21,9)
1 (3,1) 1(3,1) 5 (15,6)
S o 3 n (Vo) 1 (3,1) 4(12,5) 0 0 1 (3,1)
e 6 4 n (%)
0 2 (6,2)
0 0 0 3 (9,4%)
Bang 3.3 ehi ra ty le giam bach cau tong chiem 53,1%; ehii yeu giam bach eau dp 1 (37,5%), dp 2 (12,5%), giam bach cau tong dp 3 it gap (3,1%). Giam bach cau trung tinh thydng gap chiem 62,5%, trong do dp 3, do 4 ehiem ty le khong eao lan lydt la 12,5%; 6,2%.
Sot giam bach cau chiem 9,4%. Thieu mau cting rat hay gap chiem 75%, ehu yeu dp 1 (71,9%).
Tang men gan thydng gap mifc dp nhe, tang men gan SGPT chi gap 3 , 1 % . Khong gap ha tieu cau eung nhy khong eo doe tinh tren than. Ket qua nghien eifu cua EC0C5 E-1199 thi d nhom dydc dieu trj bo trd bang phae do 4AC-4D ty le ha bach cau da nhan trung ti'nh d6 3, 4 kha eao ehiem 45%, ty le sot ha bach cau chiem 16%.
Nhy vay so vdi ket qua ciia ECOG E-1199 thi ty te dpc tinh dp 3, 4 cung nhy sot ha bach cau ciia chiing toi it gap hdn, ket qua nay cd the do trong nghien eifu ciia chiing toi lieu hda chat dieu trj eho benh nhan ehi bang 90-95% lieu hoa ehat phac do chuan va chiing toi co sir dung thudc kich bach cau dy phong chu dpng do vay ma giam dydc ty le ha bach rau eung nhy sot ha bach rau.
V. KET LUAN
^Qua 32 benh nhan UTV giai doan II-IIIA dydc bo trd bang phac do 4AC-4D chung toi thay phac do cho b/ le song them khong benh rao, t / le song them 1,2, 3 nam lal00%; 91,4%; 86,9%;
ben canh do doe tinh tren he huyet hoc va g than chii yeu la dp 1, 2, ha bach cau trung tinh dp 3 chiem 12,5%, do 4 (6,2%), sot ha bach cau la 9,4%. Nhy vay, phae do 4AC-4D eai thien ty le song them khong benh trong dieu trj bo trd UTV giai doan II-IIIA va dpc tinh co the kiem soatdiTdc.
TAI LIEU T H A M KHAO
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2. Nguyen Van Hieu (2015). Ung thu'vii. Benh bpc ung thd, Nha xuat ban y hoc Ha Noi, 235- 255.
3. Sparano JA, Wang M, Martino S, et al. Pha III study of Doxorubicin- Cyclophosphamid followed by Paelitaxel or Docetaxei given every 3 weeks or weekly in operable breast cancer. Results of intergroup tnal E1199 [abstract]. J Clin oncol 2007, 4. Tran Hiep (2010). Nhan xet ka qua bydc dau dieu tn ung thu" vu glai doan sdm bang phau liiuat Aiichlncloss tai benh vien da khoa linh Binh Oinh, Tap chi yhoc TP Ho ChiMinh,tap 14, so 4, tr: 414 - 421, 5. Nguyen Dieu Linh ( 2 0 i 3 ) . Nghien ciiu i^u tn
ung thy vu glai doan I I - IIIA bang hoa chat bo trd phac do TAC va AC tai benh vien K. Luan an tien si y hoc. Tru'dng Dai hoc y Ha Noi.
6. Ngiiyen Van thuan, Nguyen Ba Du'c va rs (2006). Danh gia ket qua dieu tri bo trd hoa chat phac do Adriamycin-Cyclophosghamid ket hOp vOi dieu tri noi tiet tren benh nhan ung thU vu giai doan Il-m". Tap chi y hoc Thanh Pho Ho Chi Mmh, taplO, so4.
/ . LS Hong Quang (2012). Nghien ciru gia tn cua sinh thiet hach eya tren benh nhan ung thy vu.
Luan an tien sT y hoe. Trydng Dal hpc y Ha Npi.
