Loluphi ulwazi ekufuneka uyazi ngaphambi kokusebenzisa i-Erlotinib-AASraw
I-AASraw ivelisa i-Cannabidiol (CBD) ipowder kunye ne-Hemp ebalulekileyo yeoyile ngobuninzi!

Erlotinib

 

  1. Yintoni u-Erlotinib?
  2. Usebenza njani u-Erlotinib?
  3. Zeziphi izifo ezenziwa ngu-Erlotinib?
  4. Usetyenziswa njani u-Erlotinib ngoku ekliniki?
  5. Ngawaphi abaguli apho i-Erlotinib isebenzayo?
  6. Yintoni i-Erlotinib Resistance?
  7. Zithini iingozi ezinxulunyaniswa ne-Erlotinib?
  8. Zeziphi iziyobisi okanye iziSongezo ezinxibelelana no-Erlotinib?
  9. Unyango lwe-FDA oluvunyiweyo lwe-Erlotinib
  10. isishwankathelo

 

Yintoni i Erlotinib

I-Erlotinib (i-CAS:183321-74-6ikwiklasi yeziyobisi eyaziwa ngokuba yi-tyrosine kinase inhibitors. Isebenza ngokuthintela ukusebenza kweprotein ebizwa ngokuba yi-epidermal growth factor receptor (EGFR). I-EGFR ifunyenwe kumphezulu weeseli zomhlaza kunye neeseli eziqhelekileyo. Isebenza njenge "eriyali," ifumana imiqondiso evela kwezinye iiseli nakwimeko-bume exelela iseli ukuba ikhule ize yahlule. I-EGFR idlala indima ebalulekileyo ekukhuleni nasekukhuleni ngokwasemzimbeni nangaphakathi ebuntwaneni kwaye inceda ukugcina ukubuyisela okuqhelekileyo iiseli ezindala nezonakalisiweyo kubantu abadala. Nangona kunjalo, iiseli ezininzi zomhlaza zinezixa ezikhulu ngokungaqhelekanga ze-EGFR kumphezulu wazo, okanye i-EGFR yazo itshintshiwe ngokutshintsha kweDNA ephethe ikhowudi yemfuza yeprotein. Isiphumo kukuba imiqondiso evela kwi-EGFR yomelele kakhulu, ekhokelela ekukhuleni kakhulu kweeseli kunye nokwahlulahlula, uphawu lomhlaza.

 

Ingaba kwenzeka njani Erlotinib Umsebenzi? 

Inkqubo yesenzo se-antitumor ye-erlotinib ayibonakaliswanga ngokupheleleyo. I-Erlotinib inqanda i-intracellular phosphorylation ye-tyrosine kinase ehambelana nayo i-epidermal growth factor receptor (EGFR). Ukucaciswa kokuthintelwa ngokubhekisele kwezinye i-tyrosine kinase receptors akubonakaliswanga ngokupheleleyo. I-EGFR ibonakaliswe kwiseli engaphezulu kweeseli eziqhelekileyo kunye neeseli zomhlaza.

 

Zenzani Izifo Erlotinib Nyanga ikakhulu? 

(1) Umhlaza wemiphunga

I-Erlotinib kumhlaza wesifo somhlaza ongasetyenziswanga ongasetyenziswanga xa wongezwa kwi-chemotherapy uphucula ukusinda ngokubanzi nge-19%, kunye nokuphuculwa kokuqhubeka kokuhamba (PFS) ngama-29%, xa kuthelekiswa ne-chemotherapy yodwa I-US Food and Drug Administration (FDA) yamkelwe. ierlotinib Ukunyanga isifo somhlaza wemiphunga ongasasebenziyo ekuhlaleni okanye osileleyo osileleyo ubuncinci kwirejimeni yonyango yokuqala.

Kumhlaza wemiphunga, i-erlotinib ibonakalisiwe iyasebenza kwizigulana ezinazo okanye ezingenalo uguquko lwe-EGFR, kodwa kubonakala ngathi iyasebenza ngakumbi kwizigulana ezinokutshintsha kwe-EGFR. Ngokubanzi ukusinda, ukuqhubeka kokuhamba kunye nokuhlala unyaka omnye kuyafana Unyango (i-docetaxel okanye i-pemetrexed). Iqondo lokuphendula lilonke li malunga neepesenti ezingama-50 ngcono kunekhemotherapy yodidi lwesibini oluqhelekileyo. Izigulana ezingatshayiyo, kunye nabantu ababekade betshaya, abane-adenocarcinoma okanye ii-subtypes ezinje nge-BAC kunokwenzeka ukuba babe nokutshintsha kwe-EGFR, kodwa utshintsho olunokwenzeka kuzo zonke iintlobo zezigulana . Uvavanyo lokutshintsha kwe-EGFR luphuhliswe yiGenzyme.

 

(2) Umhlaza wePancretic

Ngo-Novemba u-2005, i-FDA yamkela i-erlotinib ngokudibanisa ne-gemcitabine kunyango lwe-pancreatic yomhlaza ekuhlaleni.

I-AASraw ngumenzi wobugcisa we-Erlotinib.

Nceda ucofe apha ngolwazi locaphulo: Unxibelelwano nathi

 

(3) Ukuxhathisa kunyango

U-Erlotinib ubotshelelwe kwi-ErbB1 kwisisombululo esingu-2.6A; Umbala ongaphezulu ubonakalisa i-hydrophobicity.Njengezinye i-ATP ezikhuphisanayo ezincinci ze-tyrosine kinase inhibitors, ezinje nge-imatinib kwi-CML, abaguli bakhula ngokukhawuleza. Kwimeko ye-erlotinib oku kwenzeka rhoqo kwiinyanga eziyi-8-12 ukusuka ekuqaleni konyango. Ngaphezulu kwe-50% yokuxhathisa kubangelwa kukutshintsha kwesixokelelwano sokubopha se-ATP kwisizinda se-EGFR kinase esibandakanya ukutshintshwa kwentsalela encinci ye-polar threonine ngentsalela enkulu ye-methonine engekho mthethweni (T790M) .Phantse i-20% yokunganyangeki ngamachiza kubangelwa kukukhulisa i-hepatocyte yokukhula kwe-factor receptor, eqhuba i-ERBB3 yokuxhomekeka kokusebenza kwe-PI3K.

 

Erlotinib

 

Njani Is Ewboxa Cngokukhawuleza Used In The CIlaphu?

U-Erlotinib waqale wavunywa yi-United States yokutya kunye noLawulo lweeDrug (FDA) ukuba isetyenziswe kwizigulana ezinomhlaza wesifo somhlaza wamaphaphu ongekho mncinci oye wabuya emva kolunye uhlobo lonyango. Ngo-2005, yavunywa ukuba isetyenziswe ngokudibanisa nelinye ichiza, i-gemcitabine, yomhlaza wepancreatic. Ngo-2010, ukusetyenziswa kwayo kwandisiwe ukubandakanya unyango lwezonyango kwizigulana ezinomhlaza wamaphaphu wesifo esingekho esincinci esinezifo esizinzileyo emva kwemijikelo emine yonyango ngesiyobisi esenziwe ngeplatinam, njengecisplatin okanye icarboplatin. Izigulana ezithatha i-erlotinib zihlala ziyinyamezela ichiza kakuhle. Iziphumo ebezingalindelekanga zixhaphakileyo kukuqhawuka kolusu kunye norhudo.

 

In Wyho Pati Is Ewboxa Mbucala ngasekhohlo Eyintsomi?

Kule minyaka ilishumi idlulileyo, oogqirha baye bafumana amava amaninzi nge-tyrosine kinase inhibitors, njenge-erlotinib, ethintela i-EGFR. Kuye kwacaca ngakumbi ukuba la machiza asebenza kakuhle kwizigulana ezinazo umhlaza wemiphunga ithwala uhlobo oluthile lotshintsho olukhokelela kwiprotheyini engaqhelekanga ye-EGFR. Ezi zigulana kunokwenzeka ukuba zivela kwimvelaphi yaseAsia, abasetyhini, kwaye bangaze batshaye abanomhlaza wemiphunga obizwa ngokuba yi-bronchoalveolar adenocarcinoma. Ke, ngo-2013, i-erlotinib yamkelwa njengonyango lokuqala lweli qelana lezigulana, ukuba umhlaza wabo awunakuphiliswa ngotyando.

 

Intoni Is Ewboxa RUncedo?

U-Erlotinib usebenza ngokukuko kwiseti yezigulana ezithwele utshintsho lwe-EGFR. Nangona kunjalo, naba baguli ekugqibeleni baya kuqala ukubonisa ukuqhubela phambili komhlaza emva kweenyanga ezili-12 zonyango lwe-erlotinib. Oku kungenxa yophuhliso lokuchasana neziyobisi kwiiseli zomhlaza ezisele. Kwiimeko ezininzi, ukuxhathisa kubangelwa kukuphucuka kwesibini kwiprotheyini ye-EGFR ethintela i-erlotinib ekunciphiseni i-domain ye-tyrosine kinase. Iindlela ezintsha zokunyanga ezi zigulana zibandakanya i-tyrosine kinase inhibitor efatinib esandula ukwenziwa, iyodwa okanye idityaniswe ne-cetuximab (Erbitux), ethintela i-EGFR ngendlela eyahlukileyo.

 

Zithini iingozi ezinxulunyaniswa ne-Erlotinib?

Kwizifundo, iziphumo ebezingalindelekanga ezixhaphakileyo nge-Erlotinib xa isetyenziswa njenge-monotherapy yomhlaza wamaphaphu yayirhabaxa (ichaphazela iipesenti ezingama-75 zezigulana), isifo sorhudo (iipesenti ezingama-54), ukuphelelwa ngumdla wokutya nokudinwa (52% inye). Kwisifundo seTarceva esetyenziswe ngokudibeneyo ne-gemcitabine yomhlaza wepancreatic, iziphumo ebezingalindelekanga eziqhelekileyo kukudinwa (kuchaphazela iipesenti ezingama-73 zezigulana), irhashalala (69%) kunye norhudo (48%). Uluhlu olupheleleyo lweziphumo ebezingalindelekanga kunye nezithintelo nge-Erlotinib, jonga iphetshana lephakheji.

 

Yeyiphi Diiragi okanye Sizixhobo INteract Wzi Ei-rlotinib?

I-CYP3A4 yi-enzyme esibindini esiqhekezayo kwaye sinceda ukuphelisa i-erlotinib emzimbeni. Iziyobisi ezithintela i-CYP3A4 zinokubangela amanqanaba aphezulu e-erlotinib emzimbeni, kwaye amanqanaba aphezulu anokubangela ityhefu evela kwi-erlotinib. Ezi ziyobisi zibandakanya i-atazanavir (Reyataz), i-clarithromycin (i-Biaxin), indinavir (Crixivan), itraconazole (Sporanox), ketoconazole (Nizoral), nefazodone (Serzone), nelfinavir (Viracept), ritonavir (Norvir), saquasevir (Invilase) I-telithromycin (Ketek), kunye ne-voriconazole (VFEND). Kwizigulana ezifumana la machiza, idosi esezantsi ye-erlotinib inokufuneka ukuthintela ityhefu.

Amanye amachiza andisa ukususwa kwe-erlotinib ngokwandisa umsebenzi we-CYP3A4 enzymes. Oku kunciphisa amanqanaba e-erlotinib emzimbeni kwaye kunokunciphisa ukusebenza kwayo. Imizekelo yala machiza aquka i-rifampicin (Rifadin), i-rifabutin (i-Mycobutin), i-rifapentine (i-Priftin), i-phenytoin (i-Dilantin), i-carbamazepine (i-Tegretol), i-phenobarbital kunye ne-St. La machiza kufuneka athintelwe kwizigulana ezithatha i-erlotinib, ukuba kunokwenzeka. Ukuba ezinye iziyobisi azikho ukhetho, iidosi eziphezulu ze-erlotinib zinokufuneka. Ukutshaya icuba kunciphisa uxinzelelo lwe-erlotinib egazini. Izigulana ziyacetyiswa ukuba ziyeke ukutshaya.

Iziyobisi ezinciphisa ukuveliswa kweasidi esiswini ziya kunciphisa ukufunxwa kwe-erlotinib. Ke ngoko, iiproton pump inhibitors (ii-PPI's, umzekelo, omeprazole [Prilosec, Zegerid]) akufuneki zenziwe nge-erlotinib, kwaye i-erlotinib kufuneka ifakwe iiyure ezili-10 ngaphambi kwe-H2-receptor blockers (umzekelo, ranitidine [Zantac]) okanye iiyure ezimbini ukuthatha i-H2-receptor blocker.

Ukulawulwa kwee-antacids kufuneka kwahlulwe kulawulo lwe-erlotinib ngeeyure ezininzi. U-Erlotinib unxulunyaniswe nomngcipheko wokopha, ngakumbi kwizigulana ezithatha i-warfarin (Coumadin). Izigulana ezithatha i-warfarin kufuneka zijongwe kufutshane.

 

I-FDA ivunyiwe Erlotinib impatho

Ngo-Okthobha i-18, i-2016, i-US yokutya kunye noLawulo lweeDrug yaguqula umqondiso we-erlotinib (TARCEVA, Astellas Pharm Global Development Inc.) kunyango lomhlaza wesifo somhlaza ongasencinci (I-NSCLCukunciphisa umda ekusebenziseni kwizigulana ezinamathumba aneempawu ezithile zokukhula kwe-epidermal factor factor (EGFR).

Utshintsho lweelebheli lusebenza kwizigulana ezine-NSCLC ezifumana ulondolozo okanye unyango lwelayini yesibini okanye nangaphezulu. Ezi zikhombisi ziya kunqunyanyiswa kwizigulana ezinamathumba ane-EGFR exon 19 ukususwa okanye i-exon 21 L858R yokutshintsha endaweni njengoko kufunyenwe kuvavanyo oluvunyiweyo lwe-FDA. Umgca wokuqala obonakalisiweyo ngaphambili wawunqunyelwe kwizigulana ezine-EGFR exon 19 ukususwa okanye i-exon 21 yokutshintsha endaweni.

Olu ncediso lweelebheli lusekwe kwiziphumo zovavanyo lwe-IUNO, ilingo elingenamkhethe, elingaboniyo kabini, elilawulwa yi-placebo, ulingo lwe-erlotinib olulawulwa njengonyango lokugcina kwizigulana ezingama-643 ezine-NSCLC ezihambele phambili ezingakhange zibenako ukuqhubela phambili kwesifo okanye ityhefu engamkelekanga ngexesha lemijikelezo emine iplatinotherapy yodidi lokuqala olusekwe kwiplatinam. Izigulana ezinamathumba agcina kusebenze utshintsho lwe-EGFR (exon 19 ukususwa okanye i-exon 21 L858R mutations) azifakwanga kolu vavanyo. Izigulana zazingena-1: 1 ukufumana i-erlotinib okanye i-placebo ngomlomo kube kanye yonke imihla (322 erlotinib, 321 placebo) kude kube kukuqhubela phambili kwesifo okanye ityhefu engamkelekanga. Ukulandela ukuqhubela phambili kunyango lokuqala, abaguli babefanelekile ukuba bangene kwinqanaba lelebhile evulekileyo. Iipesenti ezingama-77 zezigulana ezingahleliwe kwi-erlotinib zangena kwisigaba esivulekileyo seelebheli kwaye zafumana ichemotherapy, ngelixa i-XNUMX% yezigulana ezingena kwi-placebo zangena kwisigaba selebuli evulekileyo kwaye zafumana i-erlotinib.

Indawo yokugqibela yokuphela kwetyala yayikukusinda ngokubanzi. Iziphumo zabonisa ukuba ukusinda kulandela unyango nge-erlotinib kwakungekho bhetele kune-placebo elawulwa njengokugcinwa kwizigulana ezinesifo se-NSCLC semastatic esingagcini utshintsho lwe-EGFR. Akukho mahluko ekusindeni ngaphandle kokuqhubela phambili phakathi kwengalo ye-erlotinib kunye nengalo ye-placebo yaqwalaselwa.

I-FDA ayizukufuna iimfuno ezintsha zentengiso okanye icele ukuzibophelela emva kokuthengisa ngokusekwe kwiziphumo zolingo lwe-IUNO.

I-AASraw ngumenzi wobugcisa we-Erlotinib.

Nceda ucofe apha ngolwazi locaphulo: Unxibelelwano nathi

 

isishwankathelo

I-Erlotinib sisiyobisi sokwenziwa esenzelwe unyango lomhlaza. Kuyamkelwa ukunyanga umhlaza wemiphunga ongekho mncinci, umhlaza weprostate ongaphazamisekiyo, kunye nomhlaza wepancreatic. Ukuphonononga iziphumo ebezingalindelekanga, idosi, ukuhlangana kweziyobisi, izilumkiso kunye nokuthintela, kunye nolwazi lokhuseleko lokukhulelwa ngaphambi ukusebenzisa Erlotinib.

 

isingqiniso

[1] UThomas L. Petty, MD (2003). "Ukuchongwa kwempendulo yeThumba kunye nokuSinda nge-Erlotinib kwizigulana ezinomhlaza ongalunganga-wesifo semiphunga". Ijenali ye-Oncology yeklinikhi. Eyoku-1 (17): 3-4.

[2] "I-FDA ivuma uvavanyo lweRoche njengeCDx yeTarceva yokuNyanga abaguli abathile beNSCLC". IGenomeWeb. Ukufunyanwa kwe-10 kaJanuwari 2020.

[3] UDudek AZ, uKmak KL, uKoopmeiners J, et al. Ukuchaneka (2006). "Ukuqhaqha kwesikhumba kunye ne-bronchoalveolar histology inxibelelana noncedo lweklinikhi kwizigulana eziphathwe nge-gefitinib njengonyango lonyango lwangaphambili okanye lwe-metastatic non-small cell cancer". Umhlaza wemiphunga. 51 (1): 89–96.

[4] UJones HE, Goddard L, Gee JM, Hiscox S, Rubini M, Barrow D, Knowlden JM, Williams S, Wakeling AE, Nicholson RI: Insulin-like ukukhula factor-I receptor signaling kwaye ndafumana ukumelana ne-gefitinib (ZD1839; Iressa) in iiseli zomhlaza webele kunye neprotate yomhlaza. Umhlaza we-Endocr Relat. NgoDisemba wama-2004; 11 (4): 793-814.

[5] UKobayashi K, uHagwarawara K (2013). "Utshintsho lwe-Epidermal factor factor receptor (EGFR) kunye nonyango olwenzelwe wena kumhlaza wesifo somhlaza wamaphaphu (NSCLC)". I-Oncology ekujoliswe kuyo. Eyesi-8 (1): 27-33. ikhonkco: 10.1007 / s11523-013-0258-9. I-PMID 3591525.

[6] UCohen, uMartin H .; UJohnson, uJohn R .; Chen, Yeh-Fong; USridhara, uRajeshwari; IPazdur, uRichard (Agasti 2005). "Isishwankathelo sokuvunywa kweziyobisi ze-FDA: iipilisi ze-erlotinib (Tarceva)". Oncologist. 10 (7): 461-466.

[7] IBlum G, iGazit A, i-Levitzki A: Inxalenye yokhuphiswano lwee-inhibitors ze-IGF-1 receptor kinase. IBhayoloji. 2000 ngoDisemba 26; 39 (51): 15705-12.

[8] "Isiyobisi somhlaza: INkundla ePhakamileyo ivumela uCipla ukuba arhoxise isibheno ngokuchasene neRoche". Amaxesha oQoqosho. Ngomhla we-16 kweyeSilimela ngowama-2017.

[9] UDelbaldo C, uFaivre S, uRaymond E: [Ukukhula kwe-Epidermal factor inhibitors]. UMfu Med Interne. Ngo-2003 uJun; 24 (6): 372-83.

[10] I-Chen X, i-Ji ZL, i-Chen YZ: i-TTD: Ugcino lwedatha ekujolise kuyo kunyango. Nucleic Acids Res. Ngo-2002 uJan 1; 30 (1): 412-5.

[11] I-Filppula AM, i-Neuvonen PJ, i-Backman JT: Uvavanyo lwe-in vitro lweziphumo zokuxhomekeka kwexesha ezixhomekeke kwi-CYP2C8 kunye nomsebenzi we-CYP3A nge-protein kinase inhibitors ezilishumi elinesine. Ukuchithwa kweMetab yeziyobisi. NgoJulayi 2014; 42 (7): 1202-9. ikhonkco: 10.1124 / dmd.114.057695. Epub 2014 ngoMatshi 8.

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