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Afatinib

 

  1. Yintoni i-Afatinib?
  2. Xa sifuna i-Afatinib?
  3. Isebenza njani i-Afatinib?
  4. Ngaba i-Afatinib yamkelwe yi-FDA? Ngokuqinisekileyo
  5. Yeyiphi iRisk / Side effects Ngaba i-Afatinib izisa?
  6. Luluphi Olunye Uphando Nge-Afatinib?

 

Intoni Is Afatinib?

Afatinib (CAS: 439081-18-2sisiyobisi sonyango ekujoliswe kuso esaziwa njengeGiotrif. Isetyenziselwa ukunyanga umhlaza wamaphaphu ongekho mncinci (NSCLC) osele uqalile ukusasazeka ngaphandle kwemiphunga okanye kwamanye amalungu omzimba. Ingasetyenziselwa ukunyanga eminye imihlaza njengenxalenye yesilingo seklinikhi.

Kungcono ukufunda olu lwazi ngolwazi lwethu ngokubanzi malunga nomhlaza wemiphunga okanye uhlobo lomhlaza onawo. Ugqirha wakho uza kuthetha nawe malunga nolu nyango kunye neziphumo zalo ezinokubakho ngaphambi kokuba uvume (imvume) ukuba ufumane unyango. Ngexesha lonyango, uya kubona ugqirha womongikazi okanye umongikazi. Nguye lo sithetha ngaye xa sikhankanya ugqirha okanye umongikazi kolu lwazi.

 

Xa Sifuna Afatinib

I-Afatinib inokusetyenziselwa ukunyanga umhlaza wamaphaphu ongaqhelekanga (NSCLC) one:

Ukusasazeka kwezicubu ezikufutshane (ekuhlaleni)

Sasazeka kwamanye amalungu omzimba (phambili okanye kwimastastatic).

I-Afatinib isebenza kuphela kwiicancer ezinefom engaqhelekanga yeprotein ebizwa ngokuba yi-epidermal growth factor receptor (I-EGFR). Uvavanyo lwenziwa kwiiseli zomhlaza ezivela kwi-biopsy okanye kutyando lwangaphambili ukujonga inqanaba le-EGFR. Oku uxelela ugqirha wakho ukuba i-afatinib kungenzeka ikusebenzele.

 

Ingaba kwenzeka njani Afatinib Umsebenzi?

I-Afatinib inamandla kwaye iyakhetha, ibhlokhi yosapho ye-ErbB engenakuphinda ibuye. I-Afatinib ibophelela ngokudibeneyo kwaye ibhloka ibuye umva ukusayina kuyo yonke i-homo kunye neeheterodimers ezenziwe ngamalungu osapho e-ErbB i-EGFR (ErbB1), HER2 (ErbB2), ErbB3 kunye ne-ErbB4.

Ngokukodwa, i-afatinib ibophelela ngokudibeneyo kwimimandla ye-kinase ye-EGFR (i-ErbB1), i-HER2 (i-ErbB2), kunye ne-HER4 (i-ErbB4) kunye ne-irosversible inhibits tyrosine kinase autophosphorylation, ekhokelela ekuthotyelweni komqondiso we-ErbB. Utshintsho oluthile kwi-EGFR, kubandakanya utshintsho olunganyangekiyo kwisizinda sayo se-kinase, kunokubangela ukwanda kwe-autophosphorylation ye-receptor, ekhokelela ekusebenzeni kwe-receptor, ngamanye amaxesha ngokungabikho kokubopha kwe-ligand, kwaye inokuxhasa ukwanda kweseli kwi-NSCLC. Utshintsho olunganyangekiyo luchazwa njengolo lwenzeka kwisiseko se-kinase ye-EGFR ekhokelela ekonyukeni kokuvuselelwa kwe-receptor kwaye apho ukusebenza kuxelwa kwangaphambili yi-1) eklinikhi yokuchaphazeleka kwesisu kunye nedosi ekhuthazwayo ye-afatinib kunye / okanye 2) inhibition yokwanda kweselula okanye i-EGFR tyrosine kinase phosphorylation kugxininiso lwe-afatinib oluzinzileyo kumthamo ocetyiswayo ngokweendlela eziqinisekisiweyo. Ezona zifunyanwa zixhaphakileyo kwezi nguqulelo zenziwa endaweni ka-21 L858R endaweni yoko kunye nokucinywa okungu-19.

Ngaphaya koko, i-afatinib ibonakalise ukuthintelwa kwe-autophosphorylation kunye / okanye kwi-vitro ekwandeni kwemigca yeseli ebonisa uhlobo lwasendle lwe-EGFR nakwabo baveza i-EGFR exon 19 ekhutshiweyo yokucinywa, i-exon 21 L858R, okanye ezinye izinto ezingafaniyo ezingaguqukiyo, kugxininiso lwe-afatinib kwizigulana. Ukongeza, i-afatinib inqanda in vitro ukwanda kwemigca yeeseli ngokugqithileyo kwi-HER2.

I-AASraw ngumenzi wobugcisa we-Afatinib.

Nceda ucofe apha ngolwazi locaphulo: Unxibelelwano nathi

 

Ngaba Afatinib Yamkelwe yi-FDA? Ngokuqinisekileyo

Ukuvunywa kubonelela ngendlela entsha yonyango lodidi lwesibini kwizigulana ezinodidi lwesibini olukhulu lweseli esincinci umhlaza wemiphunga (NSCLC), emele malunga ne-20-30% yamatyala e-NSCLC

Ukuvunywa kusekwe kwiziphumo zesifundo se-LUX-Lung 8, esibonakalise ukuphucula okuphucukileyo kokuphila kunye nokuqhubeka kokuphila ngaphandle kokuthelekiswa neTarceva (erlotinib) kwizigulana ezine-squamous cell carcinoma yemiphunga

Afatinib sele yamkelwe kumazwe angaphezu kwama-60 kunyango lwezigulana ezineentlobo ezahlukileyo ze-NSCLC yotshintsho lwe-EGFR

Afatinib

Yintoni umngcipheko/Imiphumela Ngaba Afatinib Zisa? 

Izinto ezibalulekileyo ekufuneka uzikhumbule malunga neziphumo ebezingalindelekanga ze-afatinib:

Uninzi lwabantu alunakufumana zonke iziphumo ebezingalindelekanga ezidwelisiweyo.

▪ Iziphumo ebezingalindelekanga ze-Afatinib zihlala ziqikelelwa ngokuqala kwazo, ubude bexesha, kunye nobukhali bazo.

Iziphumo ebezingalindelekanga ze-Afatinib zihlala zibuyela umva kwaye ziya kuphela emva kokuba unyango lugqityiwe.

▪ Iziphumo ebezingalindelekanga ze-Afatinib zinokulawulwa. Kukho iindlela ezininzi zokunciphisa okanye ukuthintela iziphumo ebezingalindelekanga ze-afatinib.

 

Iziphumo ebezingalindelekanga zixhaphakile (zenzeka ngaphezulu kwe-30%) kwizigulana ezithatha i-afatinib:

▪ Urhudo

▪ Ukuqhuma kwamabala (iqela leemeko zolusu ezifana namabala)

Izilonda zomlomo

▪ IParonychia (usulelo lweenzipho)

▪ Umlomo owomileyo

 

Ezi ziziphumo ebezingalindelekanga eziqhelekileyo (ezenzeka nge-10-29%) kwizigulana ezifumana i-afatinib:

▪ Ukunciphisa ukutya

▪ Ukurhawuzelela

▪ Ukwehla kobunzima

▪ Impumlo iyopha

▪ ICystitis (usulelo lwesinyi)

▪ I-Cheilitis (ukudumba kwemilebe)

▪ Umkhuhlane

▪ IHypokalemia (potassium ephantsi)

▪ Isidumbu (iso elipinki)

▪ Irhinorrhea (ukuphuma kwempumlo)

▪ Ii-enzymes zesibindi eziphakamileyo

Ayizizo zonke iziphumo ebezingalindelekanga ezidweliswe apha ngasentla. Ezinye ezinqabileyo (ezenzeka ngaphantsi kweepesenti ezili-10 zezigulane) azibhalwanga apha. Soloko wazisa umboneleli wakho wezempilo ukuba ufumana naziphi na iimpawu ezingaqhelekanga.

 

Olunye uPhando malunga Afatinib?

 I-Afatinib (i-BIBW 2992) yophuhliso lomhlaza ongalunganga weseli

I-Afatinib (i-BIBW 2992), inoveli ye-aniline-quinazoline evela kuyo, engenakuphinda ibuye ibuye ijolise ekujongeni umsebenzi we-kinase wangaphakathi kuwo onke amalungu osapho e-ErbB receptor. Iziphumo zangaphambi kokubonisa zibonisa ukuba i-afatinib iyasebenza kwiimodeli zomhlaza wemiphunga, kubandakanya nezo zinokufunyanwa kwe-EGF receptor (EGFR) enganyangekiyo kwisizukulwana sokuqala se-EGFR inhibitors. I-Afatinib isaphandwa kwinkqubo ye-LUX-Lung, eza kuvavanya i-afatinib njengonyango lodidi lokuqala kwizigulana ezine-EGFR-activating mutations (LUX-Lung 2, 3 and 6) nanjengolwesibini okanye owesithathu unyango lonyango kwizigulana abafumene ukuxhathisa kwi-gefitinib kunye / okanye i-erlotinib (i-LUX-Lung 1, 4 kunye ne-5). I-LUX-Lung 1 kunye ne-2 babonakalisile, ngokwamaqela abo ekujolise kuwo, ukonyuka okubonakalayo kwinqanaba lokulawula isifo le-58 kunye ne-86%, ngokwahlukeneyo, kunye nokwandiswa okubalulekileyo kokuqhubeka kokungabikho. Olunye uvavanyo lweklinikhi yesiGaba sesi-III luyaqhubeka ukuvavanya i-afatinib ngokudibeneyo ne-paclitaxel (LUX-Lung 5), kwaye xa kuthelekiswa ne-cisplatin / pemetrexed (LUX-Lung 3) okanye i-cisplatin / gemcitabine (LUX-Lung 6).

I-AASraw ngumenzi wobugcisa we-Afatinib.

Nceda ucofe apha ngolwazi locaphulo: Unxibelelwano nathi

 

 I-Afatinib kwindawo ehamba phambili kunye ne-metastatic chordoma

Olu luvavanyo lweSigaba 2 lokufunda ngokusebenza kwefayile ye- iziyobisi zomhlaza ekujoliswe kuzo ibizwa ngokuba yi-afatinib. I-Afatinib inqanda iprotheni ye-EGFR, ekukholelwa ukuba iyabandakanyeka ekuqhubeni ukukhula kwamathumba e-chordoma. Olu phononongo luyilelwe ngokukodwa abaguli be-chordoma abaneminyaka eyi-18 okanye nangaphezulu abanezilonda eziphindaphindayo okanye zemastatic. Okwangoku ivuliwe eLeiden University Medical Centre (LUMC) nakwisibhedlele i-University College London (UCLH) kwaye izakuvulwa e-Istituto dei Nazionale Tumori (INT) eMilan kwiinyanga ezizayo. Abaphandi abaziintloko kolu phononongo nguGqirha Hans Gelderblom kwi-LUMC, uGqirha Silvia Stacchiotti kwi-INT, kunye noGqirha Sandra Strauss e-UCLH.

I-Epidermal Growth Factor Receptor (EGFR) yiprotein efumaneka kumphezulu weeseli ezithile emzimbeni wonke. Ngokuqhelekileyo, i-EGFR inceda ukulawula ukukhula kweseli kwaye idlala indima ekuphiliseni inxeba. Kwezinye i-cancer, kubandakanywa ezininzi i-chordomas, i-EGFR iyasebenza, iholele iiseli zomhlaza ukuba zande ngaphandle kolawulo.

Iziyobisi ezithintela i-EGFR ebizwa ngokuba yi "EGFR inhibitors" zamkelwe ukunyanga iintlobo ezahlukeneyo zomhlaza. I-Afatinib yi-EGFR inhibitor evunyiweyo ngoku ukunyanga umhlaza wamaphaphu ongaqhelekanga kunye nokuvavanywa kwezinye iintlobo zethumba.

I-EGFR inhibitors ezininzi ziye zaboniswa ukuba zithothise okanye ziyeke ukukhula kweeseli ze-chordoma kunye ne-chordoma tumors kwiimpuku. Kuzo zonke ii-inhibitors ze-EGFR kuvavanyiwe, i-afatinib yayiyeyona isebenzayo kwiimodeli zegundane ze-chordoma. Kwezinye iimodeli zeempuku, kuye kwacothisa ukukhula kwamathumba, ngelixa kwezinye kubangele ukuba amathumba anciphe kakhulu. Olu vavanyo lujolise ekuqinisekiseni ukuba i-afatinib inganciphisa okanye iyeke ukukhula kwezihlunu ze-chordoma kwizigulana ezinesifo esiphindaphindayo okanye se-metastatic.

 

isingqiniso

[1] ISchubert-Zsilavecz, M, iWurglics, M, Neue Arzneimittel Frühjahr 2013. (ngesiJamani)

[2] USpreitzer H (13 ngoMeyi 2008). "Neue Wirkstoffe - Tovok". I-resterreichische Apothekerzeitung (ngesiJamani) (10/2008): 498.

[3] U-Li D, u-Ambrogio L, u-Shimamura T, u-Kubo S, u-Takahashi M, u-Chirieac LR, et al. (Agasti 2008). "I-BIBW2992, i-EGFR / HER2 inhibitor engenakuphinda isebenze kwiimodeli zomhlaza wemiphunga". Oncogene. 27 (34): 4702–11. ikhonkco: 10.1038 / onc.2008.109. I-PMC 2748240. PMID 18408761.

[4] "IGiotrif: I-EPAR -Ingcaciso yeMveliso" (PDF). IArhente yamaYeza yaseYurophu. I-Boehringer Ingelheim yamanye amazwe i-GmbH. Ngomhla we-16 kweyeDwarha ngo-2013. Ibuyisiwe i-28 kaJanuwari 2014

[5] UKobayashi Y, Togashi Y, Yatabe Y, Mizuuchi H, uJangchul P, uKondo C, et al. (UDisemba 2015). "I-EGFR Exon 18 iinguqu kwiCancer Lung: I-Molecular Predictors of Augmented Sensitivity to Afatinib okanye iNeratinib xa kuthelekiswa ne-First-or Third-Generation TKIs". Uphando ngomhlaza weklinikhi. 21 (23): 5305–13. ikhonkco: 10.1158 / 1078-0432.CCR-15-1046. IINKCUKACHA:

[6] Lin Lin, Winer EP, Wheatley D, Carey LA, Houston S, Mendelson D, et al. (Juni 2012). "Isigaba sesi-II sifundo se-afatinib (i-BIBW 2992), i-ErbB blocker yosapho engenakuguqulwa, kwizigulana ezinesifo somhlaza webele se-HER2 esihamba emva kwetrastuzumab". Umhlaza wamabele uphando kunye nonyango. 133 (3): 1057-65. ikhonkco: 10.1007 / s10549-012-2003-y. I-PMID 3387495.

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