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Afatinib

 

  1. Afatinib yog dab tsi?
  2. Thaum Peb Xav Tau Afatinib?
  3. Afatinib Ua Haujlwm Li Cas?
  4. Puas yog Afatinib Pom Zoo los ntawm FDA? Ntsoov
  5. Dab Tsi Mob / Phiv Los sis Uas Afatinib Nqa?
  6. Dab Tsi Lwm Qhov Kev Tshawb Fawb Txog Afatinib?

 

Yuav ua li cas Is Afatinib?

Afatinib (CAS: 439081-18-2) yog hom tshuaj kho mob uas tseem tseem hu ua Giotrif. Nws yog siv los kho tsis mob qog nqaij hlav rau cov ntshav muaj ntshav tsawg (NSCLC) uas tau pib kis mus rau sab nraud lub ntsws lossis mus rau lwm qhov hauv lub cev. Nws kuj tseem siv tau los kho lwm tus mob qog nqaij hlav uas yog ib qho ntawm kev sim tshuaj.

Nws yog qhov zoo tshaj plaws los nyeem cov ntaub ntawv no nrog peb cov ntaub ntawv dav dav txog kev mob qog lossis hom mob cancer koj muaj. Koj tus kws kho mob yuav nrog koj tham txog cov kev kho no thiab qhov tshwm sim muaj feem ua ntej koj pom zoo (pom zoo) muaj kev kho mob. Thaum kho, koj yuav ntsib tus kws kho mob qog noj ntshav lossis tus kws tu neeg mob. Nov yog leej twg peb tau hais tseg thaum peb hais txog kws kho mob lossis kws tu neeg mob hauv cov ntaub ntawv no.

 

Thaum Peb Xav Tau Afatinib

Afatinib yuav raug siv los kho mob qog nqaij hlav cancer hauv hlwb tsis zoo-me me (NSCLC) uas muaj:

Kis mus rau cov ntaub so ntswg ib puag ncig (qib siab hauv zos)

Kis rau lwm qhov chaw ntawm lub cev (qib siab lossis metastatic).

Afatinib tsuas yog ua haujlwm rau cov qog ntshav uas muaj qhov txawv txav ntawm cov protein hu ua epidermal growth factor receptor (EGFR)). Kev kuaj yog ua tiav rau cov qog nqaij hlav cancer los ntawm kev kuaj me me lossis kev phais mob ua ntej dhau los tshawb xyuas qib EGFR. Qhov no qhia rau koj tus kws kho mob seb afatinib puas yuav ua haujlwm rau koj.

 

Ua Li Cas Afatinib Ua haujlwm?

Afatinib yog qhov muaj zog thiab xaiv, tsis muaj kev hloov pauv hauv tsev neeg ErbB blocker. Afatinib covalently khi rau thiab tsis tuaj yeem thaiv cov paib los ntawm txhua homo thiab heterodimers tsim los ntawm ErbB tsev neeg EGFR (ErbB1), HER2 (ErbB2), ErbB3 thiab ErbB4.

Hauv tshwj xeeb, afatinib covalently khi rau kinase cov chaw ntawm EGFR (ErbB1), HER2 (ErbB2), thiab HER4 (ErbB4) thiab tsis cuam tshuam qhov tsis kam tyrosine kinase autophosphorylation, uas ua rau muaj kev cuam tshuam ntawm ErbB cov paib. Qee yam kev hloov pauv hauv EGFR, suav nrog kev hloov pauv tsis-tiv thaiv nyob rau hauv nws lub kinase domain, tuaj yeem ua rau muaj autophosphorylation ntau ntxiv ntawm cov receptor, ua rau cov receptor ua kom muaj zog, qee zaum thaum tsis muaj ligand khi, thiab tuaj yeem txhawb nqa cell loj hlob hauv NSCLC. Kev tsis hloov pauv tau txhais tias yog cov tshwm sim hauv exons constituting kinase domain ntawm EGFR uas ua rau kom muaj kev ua kom muaj zog ntxiv thiab qhov twg cov kev ua tau zoo tau kwv yees los ntawm 1) cov kab mob muaj txiaj ntsig ua qog ntsws nrog cov koob tshuaj pom zoo ntawm afatinib thiab / lossis 2) kev txwv tsis pub muaj cellular proliferation. los yog EGFR tyrosine kinase phosphorylation ntawm qhov ntau ntawm afatinib muaj kev ruaj ntseg ntawm cov tshuaj pom zoo raws li cov kev qhia tau tseeb. Feem ntau pom ntawm cov kev hloov pauv yog exon 21 L858R hloov chaw thiab exon 19 tshem tawm.

Ntxiv mus, afatinib qhia txog kev cuam tshuam ntawm autophosphorylation thiab / lossis nyob rau hauv vitro loj hlob ntawm cov xovtooj ntawm hais tawm yam tsis muaj hom EGFR thiab nyob rau hauv cov lus tshaj tawm xaiv EGFR exon 19 kev hloov mus rau kev sib hloov, exon 21 L858R kev hloov pauv, lossis lwm qhov tsawg dua qhov tsis muaj kev cuam tshuam kev sib hloov, ntawm afatinib ntau hauv cov neeg mob. Tsis tas li ntawd, afatinib inhibited hauv vitro loj hlob ntawm cov xovtooj ntawm txoj kab ntau dhau hER2.

AASraw yog lub chaw tsim tshuaj kev lag luam ntawm Afatinib.

Thov nyem ntawm no rau cov ntaub ntawv hais: dawb paugHu rau peb

 

Yuav ua li cas Afatinib FDA pom zoo? Ntsoov

Kev Pom Zoo muab txoj kev xaiv thib ob rau kev kho mob rau cov neeg mob nrog lub thib ob loj tshaj plaws sub-hom ntawm cov xov tooj ntawm tes tsis mob ntsws cancer (NSCLC), sawv cev txog 20-30% ntawm NSCLC cov neeg mob

Kev pom zoo yog txiav txim siab los ntawm LUX-Lung 8 txoj kev tshawb nrhiav, uas qhia tau tias muaj kev ua neej zoo tag nrho thiab tsis muaj kev vam meej nyob nrog piv rau Tarceva (erlotinib) hauv cov neeg mob uas muaj squamous cell carcinoma ntawm ntsws

Afatinib twb tau txais kev pom zoo hauv ntau dua 60 lub teb chaws rau kev kho mob ntawm cov neeg mob uas muaj cov yam ntxwv sib txawv ntawm EGFR kev sib hloov-zoo NSCLC

Afatinib

Dab Tsi Yuav Pheej Hmoo/ Sab sij huam Puas yog Afatinib Nqa? 

Cov khoom tseem ceeb kom nco qab txog cov kev mob tshwm sim los ntawm afatinib:

People Cov neeg feem coob yuav tsis pom tag nrho ntawm afatinib phiv uas teev tseg.

▪ Afatinib phiv feem ntau tuaj yeem kwv yees hais txog lawv qhov pib, ntev, thiab mob hnyav.

Effects Afatinib phiv yuav luag txhua qhov thim rov qab thiab yuav ploj mus tom qab kev kho tiav.

Effects Afatinib phiv yuav tswj tau heev. Muaj ntau txoj hauv kev los txo qis lossis tiv thaiv qhov tshwm sim ntawm afatinib.

 

Cov kev mob tshwm sim hauv qab no yog tshwm sim (tshwm sim hauv ntau dua 30%) rau cov neeg mob noj afatinib:

. Mob plab zawv

Ne Pob txuv tawv (pawg neeg tawv nqaij zoo li pob txuv)

Outh qhov ncauj tawm

Ony Paronychia (kis mob ntsia hlau)

Mouth Qhov ncauj qhuav

 

Cov no yog cov tshwm sim tsawg dua (tshwm sim hauv 10-29%) rau cov neeg mob tau txais afatinib:

Tsis qab los noj mov

Khaus

Loss Poob phaus

▪ qhov ntswg ntshav

▪ Cystitis (zais zis)

Il Cheilitis (mob rau daim di ncauj)

▪ Ua npaws

Yp Mob Hypokalemia (ntshav qab zib tsawg)

J Mob pob ntseg (qhov muag liab)

In Kabmob Ntshav (los ntswg)

Z Kev nce siab hauv lub siab enzymes

Tsis yog tag nrho cov kev mob tshwm sim muaj npe saum toj no. Qee qhov tsis tshua muaj tshwm sim (tshwm sim hauv tsawg dua 10 feem pua ​​ntawm cov neeg mob) tsis muaj npe nyob ntawm no. Nco ntsoov qhia rau koj tus kws saib xyuas kev noj qab haus huv yog tias koj muaj cov tsos mob txawv txawv.

 

Dab Tsi Lwm Qhov Kev Tshawb Fawb Txog Afatinib?

 Afatinib (BIBW 2992) kev txhim kho hauv cov ntsws tsis mob ntsws-mob hlwb tsawg tsawg

Afatinib (BIBW 2992), tus tshiab aniline – quinazoline derivative, ruaj khov thiab tsis ncaj lub hom phiaj rau kev ua haujlwm ntawm kinase ntawm txhua tus neeg nquag ErbB receptor tsev neeg. Cov txiaj ntsig ntawm Preclinical qhia tau hais tias afatinib ua tau zoo hauv cov qauv mob ntsws, nrog rau cov uas muaj EGF receptor (EGFR) hloov pauv tau cov tshuaj tiv thaiv thawj tiam EGFR inhibitors. Afatinib tseem tab tom tshawb nrhiav hauv qhov kev pab cuam LUX-Lung, uas yuav soj ntsuam afatinib ua kev kho thib ib hauv cov neeg mob EGFR-kev hloov pauv (LUX-Lung 2, 3 thiab 6) thiab raws li txoj kev kho zaum ob - lossis thib peb hauv cov neeg mob uas tau kis cov tshuaj tiv thaiv gefitinib thiab / lossis erlotinib (LUX-Lung 1, 4 thiab 5). LUX-Lung 1 thiab 2 tau ua kom pom, hauv lawv pawg phiajcim, qhov nce ntawm cov kabmob tswj tau tus kabmob nce ntawm 58 thiab 86%, feem, thiab lub sijhawm ntev ntawm kev vam meej-tsis muaj sia nyob. Cov Kev Ntsuam Xyuas Ntxiv III tam sim no raug ntsuas tam sim no los soj ntsuam afatinib hauv kev sib xyaw nrog paclitaxel (LUX-Lub Qhov Siab 5), thiab piv nrog cisplatin / pemetrexed (LUX-Lung 3) lossis cisplatin / gemcitabine (LUX-Lung 6).

AASraw yog lub chaw tsim tshuaj kev lag luam ntawm Afatinib.

Thov nyem ntawm no rau cov ntaub ntawv hais: dawb paugHu rau peb

 

 Afatinib hauv zos siab heev thiab metastatic chordoma

Nov yog Theem 2 sim qhia txog qhov ua tau zoo ntawm a tsom cov tshuaj mob cancer hu ua afatinib. Afatinib inhibits EGFR protein, uas ntseeg tau tias yuav koom nrog kev tsav tsheb kev loj hlob ntawm chordoma hlav. Txoj kev tshawb no yog tsim tshwj xeeb rau cov neeg mob chordoma uas muaj 18 xyoo lossis laus dua nrog cov mob ua pob lossis mob pob zeb. Tam sim no qhib ntawm Leiden University Medical Center (LUMC) thiab Tsev Kawm Qib Siab University London Tsev Kho Mob (UCLH) thiab yuav qhib ntawm Istituto dei Nazionale Tumori (INT) hauv Milan lub hlis tom ntej. Tus thawj tswjfwm kev sojntsuam rau kev kawm no yog Dr. Hans Gelderblom ntawm LUMC, Dr. Silvia Stacchiotti ntawm INT, thiab Dr. Sandra Strauss ntawm UCLH.

Epidermal Growth Factor Receptor (EGFR) yog ib qhov protein nyob ntawm tej qe ncig thoob plaws lub cev. Feem ntau, EGFR pab tswj hwm kev loj hlob ntawm tes thiab ua lub luag haujlwm hauv kev kho cov qhov txhab kom zoo. Hauv qee cov qog nqaij hlav, suav nrog feem ntau chordomas, EGFR dhau los ua kev ntxim nyiam, ua rau cov kabmob kheesxaws nce mus rau qhov tsis tuaj yeem tswj tau.

Cov tshuaj uas thaiv EGFR hu ua "EGFR inhibitors" tau pom zoo kho ntau hom mob qog nqaij hlav cancer. Afatinib yog EGFR inhibitor uas tau pom zoo tam sim no los kho cov qog ntshav tsis yog-me me thiab tau raug kuaj hauv lwm cov qog ntshav.

Ob peb EGFR inhibitors tau pom tias qeeb lossis nres kev loj hlob ntawm chordoma hlwb thiab chordoma hlav hauv cov nas. Ntawm txhua qhov EGFR inhibitors tau sim, afatinib tau ua haujlwm zoo tshaj plaws hauv cov qauv nas ntawm chordoma. Hauv qee cov qauv ua niam txiv, nws ua rau qeeb ntawm txoj kev loj hlob ntawm cov qog, thaum nyob rau lwm tus nws ua rau cov qog ua kom loj dua. Qhov kev sim no txhawm rau txiav txim siab seb puas yog afatinib tuaj yeem ua rau me ntsis tuaj yeem ploj los yog tshem tawm qhov kev loj hlob ntawm cov qog chordoma hauv cov neeg mob uas muaj cov kab mob rov qab los yog mob.

 

reference

[1] Schubert-Zsilavecz, M, Wurglics, M, Neue Arzneimittel Frühjahr 2013. (hauv German)

[2] Spreitzer H (13 Tsib Hlis 2008). “Neue Wirkstoffe - Tovok”. Österreichische Apothekerzeitung (hauv German) (10/2008): 498.

[3] Li D, Ambrogio L, Shimamura T, Kubo S, Takahashi M, Chirieac LR, li al. (Lub Yim Hli 2008). "BIBW2992, ib qho tsis paub txog EGFR / HER2 inhibitor ua tau zoo nyob rau hauv kev tiv thaiv kabmob ntsws ua rau mob ntsws". Oncogene. 27 (34): 4702–11. doi: 10.1038 / onc.2008.109. PMC 2748240. PMID 18408761.

[4] “Giotrif: EPAR -Txoj Cai Qhia” (PDF). Lub Chaw Haujlwm Tshuaj Noj European. Boehringer Ingelheim International GmbH. 16 Lub Kaum Hli 2013. Tshawb Dua 28 Lub Ib Hlis 2014.

[5] Kobayashi Y, Togashi Y, Yatabe Y, Mizuuchi H, Jangchul P, Kondo C, li al. (Lub Kaum Ob Hlis 2015). "EGFR Exon 18 Cov Kev Sib Hloov Hauv Lub Cev Mob Hlwb Mob ntsws: Cov Ntshav Zog Ntawm Cov Hluav Taws Xob ntawm Augmented rhiab rau Afatinib lossis Neratinib li piv nrog Thawj- lossis Thib-TKIs Tiam Tshiab". Cov Chaw Kho Mob Soj Ntsuam. 21 (23): 5305–13. doi: 10.1158 / 1078-0432.CCR-15-1046. PMID 26206867.

[6] Lin NU, Winer EP, Wheatley D, Carey LA, Houston S, Mendelson D, li al. (Lub Rau Hli 2012). "Lub sijhawm II kawm ntawm afatinib (BIBW 2992), tus neeg tsis tuaj yeem hloov pauv ntawm ErbB tsev neeg, hauv cov neeg mob HER2-zoo metastatic mob cancer mis hloov tom qab trastuzumab". Kev Tshawb Fawb Lub Qog Mis thiab Kev Kho Mob. 133 (3): 1057–65. doi: 10.1007 / s10549-012-2003-y. PMC 3387495. PMID 22418700.

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