U tlameha ho tseba tlhaiso-leseling efe pele u sebelisa Erlotinib - AASraw
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Erlotinib

 

  1. Erlotinib ke eng?
  2. Erlotinib e Sebetsa Joang?
  3. Erlotinib Haholo-holo e Phekola Mafu Afe?
  4. Erlotinib Hajoale e Sebelisoa Joang Tleliniking?
  5. Erlotinib e Atleha Haholo ho bakuli Bafe?
  6. Khanyetso ea Erlotinib ke Eng?
  7. Likotsi Tse Amanang le Erlotinib Ke Life?
  8. Ke Lithethefatsi life kapa Lisebelisoa tse Amanang le Erlotinib?
  9. Phekolo ea FDA ea Erlotinib
  10. Summary

 

Ke eng Erlotinib

Erlotinib (CAS:183321-74-6ke ea sehlopha sa lithethefatsi tse tsejoang e le tyrosine kinase inhibitors. E sebetsa ka ho thibela ts'ebetso ea protheine e bitsoang epidermal growth factor receptor (EGFR). EGFR e fumanoa ka holim'a lisele tse ngata tsa mofetše le lisele tse tloaelehileng. E sebetsa joaloka "lenakana," e amohela matšoao ho tsoa liseleng tse ling le tikolohong e bolellang sele hore e hole le ho ikarola. EGFR e bapala karolo ea bohlokoa kholong le kholo ea bokhachane le nakong ea bongoana mme e thusa ho boloka phepelo e tloaelehileng ea lisele tsa khale le tse senyehileng ho batho ba baholo. Leha ho le joalo, lisele tse ngata tsa mofetše li na le boholo bo sa tloaelehang ba EGFR bokaholimo ba tsona, kapa EGFR ea tsona e fetotsoe ke phetoho ea DNA e nang le khoutu ea lefutso ea protheine. Phello ke hore matšoao a tsoang ho EGFR a matla haholo, a lebisang ho kholo e kholo ea lisele le karohano, letšoao la mofets'e.

 

Joang Erlotinib O sebetsa? 

Mechini ea ketso ea antitumor ea erlotinib ha e tsejoe ka botlalo. Erlotinib e thibela phosphorylation ea ka hare ho sele ea tyrosine kinase e amanang le epidermal kholo khampani e amohelang (EGFR). Ho khetheha ha thibelo mabapi le li-receptor tse ling tsa tyrosine kinase ha ho so tsejoe ka botlalo. EGFR e hlahisoa ka holim'a lisele tsa lisele tse tloaelehileng le lisele tsa mofetše.

 

Seo Mafu a se Etsang Erlotinib Haholo-holo Phekola? 

(1) Kankere ea molomo

Erlotinib ka kankere ea matšoafo e seng e nyenyane e sa bonahaleng ha e eketsoa chemotherapy e ntlafatsa bophelo ka kakaretso ka 19%, le ho pholoha ho sa tsoelang pele (PFS) ka 29%, ha e bapisoa le chemotherapy feela. letsetse bakeng sa kalafo ea mofets'e oa lehae oa kankere ea matšoafo o tsoetseng pele kapa oa metastatic o hlotsoe bonyane tekanyetso e le 'ngoe ea chemotherapy ea pele.

Kankere ea matšoafo, erlotinib e bontšitsoe e sebetsa ho bakuli ba nang le kapa ba se nang liphetoho tsa EGFR, empa e bonahala e sebetsa haholo ho bakuli ba nang le liphetoho tsa EGFR. phekolo (docetaxel kapa pemetrexed). Tekanyo ea karabelo e akaretsang e ka ba 50% ho feta chemotherapy ea bobeli ea mokokotlo. Bakuli ba sa tsubeng, le ba tsubang ba neng ba tsuba pele, ba nang le adenocarcinoma kapa li-subtypes tse kang BAC ba na le monyetla oa ho ba le liphetoho tsa EGFR, empa liphetoho li ka hlaha mefuteng eohle ea bakuli . Teko ea phetoho ea EGFR e hlahisitsoe ke Genzyme.

 

(2) Kankere ea Pancreatic

Ka Pherekhong 2005, FDA e ile ea amohela erlotinib e kopantsoe le gemcitabine bakeng sa kalafo ea mofetše oa lehae o tsoetseng pele, o ke keng oa qojoa kapa oa metastatic.

AASraw ke moetsi ea hloahloa oa Erlotinib.

Ka kopo tlanya mona bakeng sa tlhaiso-leseling e qotsitsoeng: Lethathamo la rona

 

(3) Ho hanyetsa kalafo

Erlotinib e tlamiloe ho ErbB1 ho qeto ea 2.6A; 'Mala oa bokaholimo o bonts'a hydrophobicity.Joalo ka tse ling tsa tlholisano ea ATP ea molek'hule e nyane tyrosine kinase inhibitors, joalo ka imatinib ho CML, bakuli ba qala ho hanyetsoa kapele. Tabeng ea erlotinib sena hangata se etsahala likhoeli tse 8-12 ho tloha qalong ea kalafo. Ho hanyetsoa ho fetang 50% ho bakoa ke phetoho ea pokothong e tlamang ea ATP ea domain ea EGFR kinase e kenyelletsang ho emisoa ha masala a manyenyane a polar threonine ka masalla a maholo a methapo ea methone (T790M) .Palo e ka bang 20% ​​ea ho hanyetsa lithethefatsi e bakoa ke ho hola ha hepatocyte grow factor receptor, e tsamaisang ts'ebetso ea ERBB3 e itšetlehileng ka PI3K.

 

Erlotinib

 

Joang Is Erlotinib Cka potlako Used In The Clesela?

Erlotinib e ile ea amoheloa ka lekhetlo la pele ke Tsamaiso ea Lijo le Lithethefatsi ea United States (FDA) hore e sebelisoe ho bakuli ba nang le mofetše o seng o monyane oa lisele tsa matšoafo o neng o khutletse kamora mofuta o mong oa kalafo. Ka 2005, e ile ea amoheloa hore e sebelisoe hammoho le sethethefatsi se seng, gemcitabine, bakeng sa mofetše o tsoetseng pele oa pancreatic. Ka 2010, ts'ebeliso ea eona e ile ea atolosoa ho kenyelletsa kalafo ea tlhokomelo bakeng sa bakuli ba nang le mofetše o seng o monyane oa lisele tsa matšoafo eo lefu la hae le neng le tsitsitse kamora ho phekoloa makhetlo a mane ka sethethefatsi se thehiloeng ho platinamo, joalo ka cisplatin kapa carboplatin. Bakuli ba nkang erlotinib hangata ba mamella sethethefatsi hantle. Litla-morao tse tloaelehileng ke ho phatloha ha letlalo le lets'ollo.

 

In Which Patients Is Erlotinib Mbochabela Ee fokolang?

Lilemong tse leshome tse fetileng, lingaka li fumane boiphihlelo bo boholo ka tyrosine kinase inhibitors, joalo ka erlotinib, e thibelang EGFR. Ho hlakile ka ho eketsehileng hore meriana ena e sebetsa hantle ho feta ho bakuli bao kankere ea matšoafo e na le mofuta o itseng oa phetoho o hlahisang protheine e sa tloaelehang ea EGFR. Bakuli bana ho ka etsahala hore ebe ke ba lesika la Asia, basali, ebile ha ho mohla ba tsubang ba nang le mofuta oa mofetše oa matšoafo o tsejoang ka hore ke bronchoalveolar adenocarcinoma. Kahoo, ka 2013, erlotinib e ile ea amoheloa hore e be kalafo ea pele bakeng sa sehlopha sena sa bakuli, haeba mofetše oa bona o ne o ke ke oa phekoloa ka bongaka.

 

Eng Is Erlotinib Rthuso?

Erlotinib e sebetsa haholo ho bakuli ba nang le liphetoho tsa EGFR. Leha ho le joalo, le bona bakuli qetellong ba tla qala ho bonts'a tsoelo-pele ea mofetše oa bona kamora likhoeli tse ka bang 12 tsa kalafo ea erlotinib. Sena se bakoa ke nts'etsopele ea ho hanyetsa lithethefatsi liseleng tsa mofets'e tse setseng. Maemong a mangata, khanyetso e bakoa ke nts'etsopele ea phetoho ea bobeli ho protheine ea EGFR e thibelang erlotinib ho hokela lefapheng la tyrosine kinase. Mekhoa e mecha ea ho phekola bakuli bana e kenyelletsa tyrosine kinase inhibitor afatinib e sa tsoa ntlafatsoa, ​​e le mong kapa e kopane le cetuximab (Erbitux), e thibelang EGFR ka mochini o fapaneng.

 

Likotsi Tse Amanang le Erlotinib Ke Life?

Lithutong, litla-morao tse atileng haholo le Erlotinib ha e sebelisoa e le monotherapy bakeng sa mofetše oa matšoafo e ne e le leqeba (le amang bakuli ba 75%), letshollo (54%), ho hloka takatso ea lijo le mokhathala (52% ka 'ngoe). Phuputsong ea Tarceva e sebelisitsoeng hammoho le gemcitabine bakeng sa mofetše oa pancreatic, litla-morao tse tloaelehileng ke mokhathala (o amang bakuli ba 73%), lekhopho (69%) le letshollo (48%). Bakeng sa lenane le felletseng la litla-morao le lithibelo le Erlotinib, bona pampitšana ea sephutheloana.

 

eo Dlimmete kapa Slisebelisoa Interact With Erlotinib?

CYP3A4 ke enzyme sebeteng e senyehang mme e thusa ho felisa erlotinib 'meleng. Lithethefatsi tse thibelang CYP3A4 li ka baka maemo a phahameng a erlotinib 'meleng,' me maemo a phahameng a ka baka chefo e tsoang ho erlotinib. Lithethefatsi tse joalo li kenyelletsa atazanavir (Reyataz), clarithromycin (Biaxin), indinavir (Crixivan), itraconazole (Sporanox), ketoconazole (Nizoral), nefazodone (Serzone), nelfinavir (Viracept), ritonavir (Norvir), saquasevir (Invvase) telithromycin (Ketek), le voriconazole (VFEND). Bakeng sa bakuli ba fumanang lithethefatsi tsena, ho ka hlokahala tekanyo e tlase ea erlotinib ho thibela chefo.

Lithethefatsi tse ling li eketsa ho felisoa ha erlotinib ka ho eketsa ts'ebetso ea li-enzyme tsa CYP3A4. Sena se fokotsa maemo a erlotinib 'meleng mme se ka fokotsa sephetho sa ona. Mehlala ea lithethefatsi tse joalo e kenyelletsa rifampicin (Rifadin), rifabutin (Mycobutin), rifapentine (Priftin), phenytoin (Dilantin), carbamazepine (Tegretol), phenobarbital le St. John's Wort. Meriana ena e lokela ho qojoa ho bakuli ba nkang erlotinib, ha ho khonahala. Haeba meriana e meng e se khetho, ho ka hlokahala litekanyo tse phahameng tsa erlotinib. Ho tsuba sakerete ho boetse ho fokotsa mohopolo oa erlotinib maling. Bakuli ba eletsoa hore ba tlohele ho tsuba.

Lithethefatsi tse fokotsang tlhahiso ea asiti ka mpeng li tla fokotsa ho kenella ha erlotinib. Ka hona, proton pump inhibitors (mohlala, li-PPI, omeprazole [Prilosec, Zegerid]) ha ea lokela ho fuoa le erlotinib, mme erlotinib e lokela ho fuoa lihora tse 10 pele ho li-block block tsa H2 (mohlala, ranitidine [Zantac]) kapa lihora tse peli kamora moo. ho nka block block ea H2.

Tsamaiso ea li-antacids e lokela ho arohanngoa le tsamaiso ea erlotinib ka lihora tse 'maloa. Erlotinib e amahanngoa le kotsi e eketsehileng ea ho tsoa mali, haholo ho bakuli ba nkang warfarin (Coumadin). Bakuli ba nkang warfarin ba lokela ho beoa leihlo haufi-ufi.

 

FDA E amohetse Erlotinib Treatment

Ka la 18 Mphalane 2016, Tsamaiso ea Lijo le Lithethefatsi ea Amerika e ile ea fetola sesupo sa erlotinib (TARCEVA, Astellas Pharm Global Development Inc.) bakeng sa kalafo ea mofets'e o seng o monyane oa lisele tsa matšoafo (NSCLC) ho fokotsa ts'ebeliso ho bakuli bao lihlahala tsa bona li nang le phetoho e khethehileng ea li-epidermal growth factor receptor (EGFR).

Phetoho ea ho ngola e sebetsa ho bakuli ba nang le NSCLC ba fumanang tlhokomelo kapa kalafo ea mohala oa bobeli kapa o moholo. Matšoao ana a tla lekanyetsoa feela ho bakuli bao lihlahala tsa bona li nang le tloso ea EGFR exon 19 kapa li-exon 21 L858R tse fetotsoeng joalo ka ha ho fumanoe ke tlhahlobo e lumelletsoeng ke FDA. Pontšo ea mohala oa pele pejana e ne e lekantsoe ho bakuli ba nang le tloso ea EGFR exon 19 kapa liphetoho tse 21 tsa phetoho.

Tlatsetso ena ea ho ngola e ipapisitse le sephetho sa teko ea IUNO, teko ea erlotinib e sebetsitsoeng joalo ka kalafo ea tlhokomelo ho bakuli ba 643 ba nang le NSCLC e tsoetseng pele ba neng ba e-so ho ka ba le ts'oaetso ea mafu kapa chefo e sa amoheleheng nakong ea lipotoloho tse nne tsa chemotherapy ea methapo ea pele ea platinamo. Bakuli bao lihlahala tsa bona li neng li kentse liphetoho tsa EGFR (exon 19 deletions or exon 21 L858R mutations) ba ile ba qheleloa ka thoko tekong ena. Bakuli ba ne ba entsoe 1: 1 ho amohela erlotinib kapa placebo ka molomo hang ka letsatsi (322 erlotinib, 321 placebo) ho fihlela tsoelo-pele ea mafu kapa chefo e sa amoheleheng. Kamora tsoelo-pele ea kalafo ea pele, bakuli ba ne ba tšoaneleha ho kena mohatong o bulehileng. Liphesente tse mashome a mahlano tsa bakuli ba kenang erlotinib ba ile ba kena mohatong o bulehileng 'me ba fumana chemotherapy, ha bakuli ba 77% ba hlophiselitsoe ho placebo ba kena mohatong o bulehileng mme ba amohela erlotinib.

Sephetho sa mantlha sa nyeoe e bile ho pholoha ka kakaretso. Liphetho li bonts'itse hore ho pholoha kamora kalafo ea erlotinib ho ne ho se betere ho feta placebo e tsamaisoang e le tlhokomelo ho bakuli ba nang le lihlahala tsa metastatic NSCLC tse sa bolokeng liphetoho tse sebelisang EGFR. Ha ho phapang pakeng tsa phallo e se nang tsoelo-pele lipakeng tsa letsoho la erlotinib le letsoho la placebo le bonoeng.

FDA e ke ke ea hloka litlhoko tse ncha tsa kamora ho bapatsa kapa ea kopa boitlamo ba kamora papatso ho ipapisitse le sephetho sa nyeoe ea IUNO.

AASraw ke moetsi ea hloahloa oa Erlotinib.

Ka kopo tlanya mona bakeng sa tlhaiso-leseling e qotsitsoeng: Lethathamo la rona

 

Summary

Erlotinib ke sethethefatsi se entsoeng bakeng sa kalafo ea mofetše. E amohetsoe ho alafa mofetše o seng o monyane oa lisele tsa matšoafo, mofets'e oa "metastatic" o tsoetseng pele o sa sebetseng le mofetše oa pancreatic. Hlahloba litla-morao, litekanyetso, litšebelisano tsa lithethefatsi, litemoso le litemoso, le tlhaiso-leseling ka polokeho ea bokhachane pele tshebediso Erlotinib.

 

Reference

[1] Thomas L. Petty, MD (2003). "Liqeto tsa karabelo ea hlahala le ho pholoha le Erlotinib ho bakuli ba nang le mofets'e o seng oa lisele tse nyane" Leqephe la Clinical Oncology. 1 (17): 3-4.

[2] "FDA e Amohela Teko ea Roche joalo ka CDx bakeng sa Tarceva ea ho Phekola Bakuli ba Bang ba NSCLC". GenomeWeb. E khutlisitsoe ka la 10 Pherekhong 2020.

[3] Dudek AZ, Kmak KL, Koopmeiners J, le al. (2006). "Ho phatloha ha letlalo le bronchoalveolar histology ho amahanngoa le melemo ea bongaka ho bakuli ba alafshoang ka gefitinib e le kalafo bakeng sa mofets'e o neng o tšoeroe pele kapa kankere ea methapo e seng e nyane ea mofets'e". Kankere ea Lung. 51 (1): 89-96.

[4] Jones HE, Goddard L, Gee JM, Hiscox S, Rubini M, Barrow D, Knowlden JM, Williams S, Wakeling AE, Nicholson RI: Insulin-like factor factor-I receptor signaling mme ke fumane ho hanyetsa gefitinib (ZD1839; Iressa) ho lisele tsa kankere ea matsoele le ea senya ea motho. Kankere ea Endocr Relat. Lilemo tsa 2004; 11 (4): 793-814.

[5] Kobayashi K, Hagiwara K (2013). "Phetoho ea Epidermal factor factor (EGFR) le kalafo e ikhethileng ho mofets'e o tsoetseng pele oa nonsmall cell cancer (NSCLC)". Oncology e shebiloeng. 8 (1): 27-33. doi: 10.1007 / s11523-013-0258-9. PMC 3591525. PMID 23361373.

[6] Cohen, Martin H .; Johnson, John R .; Chen, Yeh-Fong; Sridhara, Rajeshwari; Pazdur, Richard (Phato 2005). "Kakaretso ea tumello ea lithethefatsi ea FDA: matlapa a erlotinib (Tarceva)". Ngaka ea Oncologist. 10 (7): 461-466.

[7] Blum G, Gazit A, Levitzki A: Substrate tlholisano ea li-inhibitors ea IGF-1 receptor kinase. Lik'hemik'hale. 2000 Phato 26; 39 (51): 15705-12.

[8] "Lithethefatsi tsa mofets'e: Lekhotla le ka Holimo-limo le lumella Cipla ho hula boipiletso khahlanong le Roche". Linako Tsa Moruo. La 16 Phuptjane 2017. E bolokiloe ho tsa mantlha ka la 24 Tšitoe 2019. E khutlisitsoe ka la 23 Tšitoe 2019.

[9] Delbaldo C, Faivre S, Raymond E: [Epidermal growth factor inhibitors]. Rev Med Interne. 2003 Pherekano; 24 (6): 372-83.

[10] Chen X, Ji ZL, Chen YZ: TTD: Database ea Target ea Phekolo. Nucleic Acids Res. 2002 Pherekhong 1; 30 (1): 412-5.

[11] Filppula AM, Neuvonen PJ, Backman JT: Tekolo ea in vitro ea litlamorao tse itšetlehileng ka nako ho CYP2C8 le ts'ebetso ea CYP3A ka li-protein kinase inhibitors tse leshome le metso e mene. Ho Laola Metab ea Lithethefatsi. 2014 Phupu; 42 (7): 1202-9. doi: 10.1124 / dmd.114.057695. Sephetho 2014 Apr 8.

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