Page 79 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg

genotype and c g o e mn o p t l y e p t e e a n d dcoihmydprleotpeyrimi dinheydropyrimi deinheydrogenas ededheyfdicrioegnecny.as Iendt eJ fCicainecnecry.
ref. 3 – FU,
r me of . n 3 o –/ c F o Um , b mMoenuole/ncdoimjkbs MD e e t u l a e l n . d i j k s DPretraela. tment Psererutrmeautrmaceinl t s c e o r n u c me n u t r r a a t c i i o l n ca os na c pe rnet dr ai ct ti o o nr aosf saepvreerdeicatnodr of a f t s a e l v e r e a n d falutoarl opyrimidi fnleu-oarsospoycriaimteidi ntoex-iacsitsyo.ciated tBorxJicCitayn.cer
B2 0r 1J 7C ; a1 n1 c6 e: 1r 4 1 250-2147.;116:141 5P-u2b4M. ed PMubIMD:ed P28M4I2D7:087. 28427087.
3) during the second cycle. Because this was most
l 3 i k ) e d l u y r c i n a g u s t e h d e b s e y c o o x n a d l i p c y l a c t l i e n . , B t h e c e a o u x s a e l i t p h l a i s t i w n a d s o ms e o ws t a s dlikeeclryeacaseudsetdo b7y5%oxfarloipmlathine, thierdoxcayclilpelaotninwdaordses awnads diescroenatsienduetdo a7f5t%erftrhoemsitxhteh tchyicrdle.cycle onwards and Tdhisecodnotsien-uceodrraefctteerdthAeUsCixotfh5c-yFcUlei.n this patient was 1Th1e.2d7o1%se-ocfotrhreatctoefdcAonUtCrolfp5a-tFiUenitns.this patient was H11e.r2g7e1n%otoyfptehawtaosf*c2oAn/t(rdoul plaictiaetniotsn. of exon 17 and 1H8e)r. genotype was *2A/(duplication of exon 17 and 18).
NOTE: The patient was initially genotyped for *2A, *N1O3T,Ec:.2T8h4e6pAa>tTieanntdwca.s12in3i6tiGal>lyAg. eAndodtityipoendalfogern*e2A, v*a1r3ia, cn.t2s8w4e6rAe>nToatnfdouc.n1d23b6yGs>eAqu. Aendcdiintigoonfalaglle2n3e cvoardiianngtsexwoenrseanodt floaunnkdinbgyinsterqouneicnrceinggioonfs,aallf2te3r wcohdicinhgceoxpoynnsuamndbeflrasnokfinsgeqinuternocneics rweegrioenasn, alfytseerd. which copy numbers of sequences were analysed. 1606 *2A-negative patients from Deenen 2016 were 1ge6n0o6t*y2pAed-nfeograotitvhepr agteinenetvsafrioamntsD.eenen 2016 were gTeonxioctityypewdasfodreofitnhedr gaesntoexvicairtiyangtrsa.de ≥ 3, global Ttoxiiciity awsasndyetfoinxeicditya,s htoxspiciitayligsraatdioen≥a3s ,toglxoicbiatyl troelxaicteitdy haos sapniytatloisxaitciotyn,.hOonslpyitoaulitscaotmioensadsutroixnigcithye first rceylcaleteodfhcohsepmitoatlihseartaiopny. wOenrlye oinuctlcuodmede.s during the first cOyRcslewoefrcehaedmjuosttheedrafopryawger,eseinxcalundetdre. atment OreRgsimwenr.e adjusted for age, sex and treatment regimen.
Genotyping:
G- 1 e 9 n o c t a y r p r i i e n r g s : o f c . 2 8 4 6 A > T
- 139cacrarireiresrsoof f*1c.32846A>T
- 538cacrarireiresrsoof f*1c.31236A>G
- 58 carriers of c.1236A>G
Results:
ReRseuslutslt: for carriers compared to non-carriers of the
gRensueltvaforiracnatr:riers compared to non-carriers of the
Supplement
pharmacokinetically- g puhiadremdadcoskeinetically- agudimdeindisdtroasteion, eadnmabilneistsravtieon, felnuaobrolepsysraimveidine tflrueoartompeynritmwiditihne atrdeeaqtmuaetnetdwruitgh
ea dx pe oq su ua r t e e i dn r u g ceoxpmopsluerteliynDPD dcoemficpielentteplyaDtiPenDts.’ deficient patients.’ Dose-corrected AUC vDeorseu-scogrerneectaecdtiAviUtyC 2ve: rgseunsegaecnte. activity 02: 1ge1n2e71a%ct.
0A : u 1t h1 o2 r7 s 1’ %c o n c l u s i o n : ‘ANuotnheorosf’ cthoenclusion: i‘nNdoinveidoufalthDePYD ivnadriavindtusawl DerPeYfDound tvoarbiaenatsswoceiraetefoduwnidth gtolobealasesvoecriaeted with tg ol ox bi c ai tl ys . e Fv oe r r e
ct o. 2x8i c4i t6yA. >FTo ra n d c.12687496TA>GT and co.1m67b9inTe>dG, there was ecovimdebnincedf,otrhaenre was aesvsidoecniacteiofnorwaitnh galsosboacilasteiovnerwe ith
tg ol ox bi c ai tl ys . e I vn e ar ed d i t i o n , tDoPxYicDitcy.1I6n7a9dTd>iGtion, Da l P o Y n D e c w . 1 a 6 s 7 a 9 s T s o > c G i a t e d waloitnhehwaeams astosolocgiaicteald two i xt hi c i ht ya . e’ m a t o l o g i c a l toxicity.’
4
Int J Cancer. I2n0t1J8CJancer. 21051;184J2a(n2):424 1-453;104.P2u(2b)M:4e2d4 -P4M3 0I D. P: u b M e d P28M9I2D9:491. 28929491.
Level of eL ev vi de el no cf e secvoidre:n4ce score: 4 gene act. 1ge-1n.e5:act. 1C -T1C. -5A: E 4 CTC-AE 4
gene varianto:utcome vgaernieant outcome cv.a2r8ia4n6tA global toxicity >c.T2846A global toxicity >T
gastrointestinal toxicity hgasetmroaintotelosgtincal toxicity haematological toxicity
hospitalisation *13 gh l o o s b p a i t l a t l o i s x a i c t i i t o y n
*13 galosbtraolitnotxeisctitinyal toxicity gastrointestinal toxicity
haematological toxicity haematological toxicity hospitalisation hospitalisation
ORadj (95% CO I R) a d j ( 9 5 % NC I S ) , t r e n d f N o S r , a t nr e n d ifnocrraenase (inpc=r0e.a0s9e5) N(pS=0.095) NS, trend Nf o S r , a t nr e n d finocrraenase i(npc=r0e.a0s6e6) N(pS=0.066) N NS
NS, trend
f N o S r , a t nr e n d ifnocrraenase (inpc=r0e.a0s9e0) 2(p4=.90.(019.704) - 32544.9) (1S.)74- N3 5 S 4 , ) t r ( e S n ) d
f N o S r , a t nr e n d for an
table continues
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