Kedu ozi ị ga-ama tupu i jiri Erlotinib - AASraw
AASraw na-emepụta Cannabidiol (CBD) ntụ ntụ na Hemp Ezigbo Mmanụ na nnukwu!

Erlotinib

 

  1. Gịnị bụ Erlotinib?
  2. Kedu ka Erlotinib si arụ ọrụ?
  3. Olee Ọrịa Erlotinib Na-agwọkarị
  4. Kedụ ka Erlotinib si arụ ọrụ ugbu a n'ụlọ ọgwụ?
  5. Kedu ndị ọrịa Erlotinib kacha arụ ọrụ?
  6. Kedu ihe bụ nguzogide Erlotinib?
  7. Kedu ihe ize ndụ ndị metụtara Erlotinib?
  8. Kedu ọgwụ ọjọọ ma ọ bụ mgbakwunye nwere mmekọrịta na Erlotinib?
  9. FDA kwadoro Erlotinib ọgwụgwọ
  10. Summary

 

Gịnị bụ Erlotinib

Erlotinib (CAS:183321-74-6) bụ nke otu ọgwụ ọgwụ ọjọọ a maara dị ka ndị na-emechi tyrosine kinase. Ọ na - arụ ọrụ site na igbochi ọrụ nke protein a na - akpọ epidermal growth factor receptor (EGFR). A na-ahụ EGFR n’elu ọtụtụ sel kansa yana sel ndị ọzọ. Ọ na-arụ ọrụ dị ka "antenna," na-enweta akara sitere na sel ndị ọzọ na gburugburu ebe obibi na-agwa sel ka ọ too ma kee. EGFR na-arụ ọrụ dị mkpa na uto na mmepe tupu ị mụọ nwa na n'oge ọ bụ nwata ma na-enyere aka ịnọgide na-agbanwe agbanwe nke ochie na mkpụrụ ndụ mebiri emebi na ndị okenye. Otú ọ dị, ọtụtụ mkpụrụ ndụ cancer nwere ọtụtụ EGFR n'elu ha, ma ọ bụ EGFR ha agbanweela site na mgbanwe nke DNA nke na-ebu mkpụrụ ndụ mkpụrụ ndụ maka protein. Ihe si na ya pụta bụ na akara ndị na-abịa site na EGFR siri ike nke ukwuu, na-eduga na uto mkpụrụ ndụ oke na nkewa, njirimara nke kansa.

 

Olee otú Erlotinib Ọrụ? 

Achọpụtaghị usoro nke antitumor na-arụ ọrụ nke erlotinib. Erlotinib na-egbochi intracellular phosphorylation nke tyrosine kinase metụtara na epidermal ibu ihe nnabata (EGFR). Achọpụtachaghị oke mgbochi banyere ndị ọzọ na-anabata tyrosine kinase. Egosiputara EGFR na sel sel nke sel na nke kansa.

 

Ihe Ọrịa Na-eme Erlotinib Ọkachasị? 

(1) Ọrịa kansa

Erlotinib na cancer cancer na-abụghị obere cell cancer mgbe etinyere ya na chemotherapy na-eme ka ndụ dum dịkwuo elu site na 19%, na ọganihu na-enweghị ọganihu (PFS) site na 29%, ma e jiri ya tụnyere ọgwụ naanị. erlotinib maka ọgwụgwọ nke ọrịa kansa na-enweghị obere cell cancer nke dara ma ọ dịkarịa ala otu usoro ọgwụgwọ chemotherapy.

N'ime ọrịa cancer akpa ume, egosila na erlotinib dị irè na ndị ọrịa nwere ma ọ bụ na-enweghị mmụba EGFR, mana ọ dị ka ọ dị irè karị na ndị ọrịa nwere mgbanwe EGFR. ọgwụgwọ (docetaxel ma ọ bụ pemetrexed). Ihe nzaghachi zuru oke bụ ihe dị ka 50% ka mma karịa usoro ọgwụgwọ nke abụọ. . E mepụtara ule maka mgbanwe EGFR site na Genzyme.

 

(2) Ọrịa Pancreatic

Na Nọvemba 2005, FDA kwadoro erlotinib yana gemcitabine maka ọgwụgwọ nke ọrịa kansa na-aga n'ihu, nke na-enweghị ike ịgbanwe, ma ọ bụ metastatic pancreatic.

 

(3) Iguzogide ọgwụgwọ

Erlotinib jikọtara ya na ErbB1 na mkpebi 2.6A; agba elu na-egosi hydrophobicity. Dị ka ndị ọzọ na ATP na-asọmpi obere molecule tyrosine kinase inhibitors, dị ka imatinib na CML, ndị ọrịa na-amalite ngwa ngwa. N'ihe banyere erlotinib nke a na-eme na ọnwa 8-12 site na mmalite ọgwụgwọ. Ihe karịrị 50% nke nguzogide bụ ihe kpatara ntụgharị na ATP njikọ nke EGFR kinase ngalaba metụtara ngbanwe nke obere pola threonine residue na nnukwu nonpolar methionine residue (T790M). Odika 20% nke na-eguzogide ọgwụ na-eme site na amplification nke hepatocyte ibu ihe nnata ihe nnabata, nke na-eme ka ọrụ ERBB3 dabere na PI3K.

 

Erlotinib

 

Kedu Is Emmmmmmmmmmmmm Cmgbe Used In The Clinik?

Ndị United States Food and Drug Administration (FDA) nabatara Erlotinib na mbụ maka ndị ọrịa nwere ọrịa kansa na-abụghị obere cell cancer bụ ndị laghachiri mgbe opekata mpe ụdị ọgwụgwọ ọzọ. Na 2005, akwadoro ka ejiri ya na ọgwụ ọzọ, gemcitabine, maka ọrịa cancer pancreatic. Na 2010, ojiji ya gbasaa iji gụnye ọgwụgwọ mmezi maka ndị ọrịa nwere nnukwu ọrịa cancer na-abụghị obere cell cancer bụ onye ọrịa ya kwụsiri ike mgbe usoro ọgwụgwọ anọ dị na ọgwụ platinum, dị ka cisplatin ma ọ bụ karboplatin. Ndị ọrịa na-erlotinib na-anabata ọgwụ ahụ nke ọma. Mmetụta kachasị emetụta bụ akpụkpọ anụ na afọ ọsịsa.

 

In Wikwe Pna ndị isi Is Emmmmmmmmmmmmm MIberibe Ena-arụ ọrụ?

N'ime afọ iri gara aga, ndị dọkịta enwetawo ahụmịhe dị ukwuu na ndị na-emechi tyrosine kinase, dị ka erlotinib, nke na-egbochi EGFR. Ọ bịara doo anya na ọgwụ ndị a kachasị arụ ọrụ na ndị ọrịa kansa cancer nwere otu ụdị mmụgharị nke na-ebute protein EGFR na-adịghị mma. Ndị ọrịa a yikarịrị ka ha sitere na agbụrụ Asia, ụmụ nwanyị, yana ndị na-ese anwụrụ ọkụ nwere ụdị ọrịa kansa akpa ume nke a maara dị ka bronchoalveolar adenocarcinoma. Ya mere, na 2013, erlotinib ka akwadoro ka ọ bụrụ ọgwụgwọ izizi maka ngalaba a nke ndị ọrịa, ma ọ bụrụ na enweghi ike ịgwọ ọrịa kansa ha.

 

Kedu Is Emmmmmmmmmmmmm Rnkwado?

Erlotinib dị oke irè na mpaghara nke ndị ọrịa na-ebu mgbanwe EGFR. Otú ọ dị, ọbụna ndị ọrịa a ga-emesị malite igosipụta ọganihu nke kansa ha mgbe ihe dị ka ọnwa 12 nke ọgwụgwọ erlotinib gasịrị. Nke a bụ n'ihi mmepe nke iguzogide ọgwụ ahụ na mkpụrụ ndụ kansa cancer. N'ọtụtụ ọnọdụ, mmegide na-esite na mmepe nke mgbanwe nke abụọ na protein EGFR nke na-egbochi erlotinib ịbanye na ngalaba tyrosine kinase. Zọ ọhụụ ọhụụ maka ịgwọ ndị ọrịa a gụnyere tyatinine kinase inhibitor afatinib, naanị ya ma ọ bụ yana cetuximab (Erbitux), nke na-egbochi EGFR site na usoro dị iche.

 

Kedu ihe ize ndụ ndị metụtara Erlotinib?

N'ime ọmụmụ ihe, mmetụta kachasị emetụta ya na Erlotinib mgbe ejiri ya mee ihe maka monotherapy maka kansa cancer bụ ọkụ ọkụ (na-emetụta 75% nke ndị ọrịa), afọ ọsịsa (54%), agụụ na ike ọgwụgwụ (52% ọ bụla). Na nyocha nke Tarceva ejiri gemcitabine mee ihe maka kansa pancreatic, mmetụta ndị kachasị emetụta bụ ike ọgwụgwụ (na-emetụta 73% nke ndị ọrịa), ọkụ ọkụ (69%) na afọ ọsịsa (48%). Maka ndepụta ọghọm na mmachi na Erlotinib, lee mpempe akwụkwọ ngwugwu.

 

nke Drugs ma ọ bụ Smmeju Intecha Wimp Enkechi?

CYP3A4 bụ enzyme na imeju na-agbaji ma na-enyere aka iwepụ erlotinib site na ahụ. Ọgwụ ndị na-egbochi CYP3A4 nwere ike ime ka erlotinib dị elu na ahụ, na nnukwu ọkwa nwere ike ibute nsị site na erlotinib. Drugsdị ọgwụ ndị a gụnyere atazanavir (Reyataz), clarithromycin (Biaxin), indinavir (Crixivan), itraconazole (Sporanox), ketoconazole (Nizoral), nefazodone (Serzone), nelfinavir (Viracept), ritonavir (Norvir), Invavir; telithromycin (Ketek), na voriconazole (VFEND). Na ndị ọrịa na-anata ọgwụ ndị a, enwere ike ịdị obere erlotinib iji gbochie nsị.

Drugsfọdụ ọgwụ na-eme ka mkpochapụ nke erlotinib dịkwuo elu site na ịba ụba ọrụ nke CYP3A4 enzymes. Nke a na - ebelata ogo erlotinib na ahụ ma nwee ike belata mmetụta ya. Ihe atụ nke ọgwụ ndị dị otú ahụ gụnyere rifampicin (Rifadin), rifabutin (Mycobutin), rifapentine (Priftin), phenytoin (Dilantin), carbamazepine (Tegretol), phenobarbital na St. John's Wort. A ghaghị izere ọgwụ ndị a na ndị ọrịa na-ewere erlotinib, ma ọ bụrụ na ọ ga-ekwe omume. Ọ bụrụ na ọgwụ ndị ọzọ abụghị nhọrọ, enwere ike ịchọ ọgwụ dị elu nke erlotinib. Sịga na-ebelata ịta erlotinib n'ime ọbara. A dụrụ ndị ọrịa ka ha kwụsị ị smokingụ sịga.

Ọgwụ nke na-ebelata mmepụta nke acid n'ime afọ ga-ebelata absorption nke erlotinib. Ya mere, ekwesighi ka erlotinib gbochie proton pump inhibitors (PPI's, dịka ọmụmaatụ, omeprazole [Prilosec, Zegerid]), erlotinib kwesịrị inye 10 awa tupu ndị na-egbochi H2-receptor blockers (dịka ọmụmaatụ, ranitidine [Zantac]) ma ọ bụ elekere abụọ mgbe na-ewere H2-receptor blocker.

Ochichi nke antacids kwesiri ka ewepu ya na ochichi nke erlotinib site na otutu awa. Ejikọtara Erlotinib na ọnụọgụ ọbara na-arịwanye elu, ọkachasị na ndị ọrịa na-ewere warfarin (Coumadin). Ọrịa na-warfarin kwesịrị ekwu anya.

 

FDA kwadoro Erlotinib Ọgwụgwọ

Na October 18, 2016, US Food and Drug Administration gbanwere ihe ngosi maka erlotinib (TARCEVA, Astellas Pharm Global Development Inc.) maka ọgwụgwọ nke ọrịa kansa na-abụghị obere cell (NSCLC) iji belata ndị ọrịa bụ ndị etuto ha nwere mmụba ihe na-akpata epidermal growth receptor (EGFR).

Mgbanwe aha a na-emetụta ndị ọrịa nwere NSCLC na-enweta mmezi ma ọ bụ ọgwụgwọ nke abụọ ma ọ bụ karịa. Ihe ngosi ndị a ga-ejedebe na ndị ọrịa ahụ etuto ha nwere EGFR exon nhichapụ 19 ma ọ bụ gbanwee 21 L858R ngbanwe ngbanwe dị ka nyocha nke FDA gosipụtara. Ihe ngosi akara nke mbụ na-ejedebe na ndị ọrịa nwere nhichapụ EGFR exon 19 ma ọ bụ ntụgharị 21 mgbanwe mgbanwe.

Ihe mgbakwunye ntinye aha a dabere na nsonaazụ nke ọnwụnwa IUNO, nke a na-ahụkarị, nke abụọ kpuru ìsì, nke a na-achịkwa ebebo, nnwale nke erlotinib nke a na-eme dị ka ọgwụgwọ mmezi na ndị ọrịa 643 nwere nnukwu NSCLC ndị na-enwetabeghị ọrịa ọrịa ma ọ bụ nsị na-adịghị anakwere na ya n'oge usoro anọ nke usoro mbu nke dabeere na platinum. Ndị ọrịa ndị etuto ha nwere na-arụ ọrụ mgbanwe EGFR (nhichapụ 19 exon ma ọ bụ ntụgharị 21 L858R exon) ewepụrụ na ikpe a. Ejiri 1: 1 mechie ndị ọrịa iji nweta erlotinib ma ọ bụ placebo ọnụ otu ugboro kwa ụbọchị (322 erlotinib, 321 placebo) ruo mgbe ọrịa na-aga n'ihu ma ọ bụ na-adịghị anabata toxicity. N'ịgbaso ịga n'ihu na ọgwụgwọ mbụ, ndị ọrịa ruru eru ịbanye na akara ngosi. Pasent 77 nke ndị ọrịa na-esiteghị na erlotinib abanye na ngalaba mmeghe ma nata chemotherapy, ebe XNUMX% nke ndị ọrịa na-etinye onwe ha na placebo abanye na ngalaba mmeghe ma nata erlotinib.

Isi ikpe nke ikpe ahụ bụ nlanarị n'ozuzu ya. Nsonaazụ gosipụtara na nlanarị na-esote ọgwụgwọ na erlotinib adịghị mma karịa placebo a na-elekọta dị ka ndozi na ndị ọrịa nwere etuto NSCLC anaghị ebute EGFR-na-emegharị mmụba. Enweghị ọdịiche dị na nnwere onwe na-enweghị ọganihu n'etiti ogwe aka erlotinib na ogwe aka placebo.

FDA agaghị achọ ahịa azụmaahịa ọhụụ ma ọ bụ rịọ maka itinye akwụkwọ maka azụmaahịa dabere na nsonaazụ ikpe IUNO.

 

Summary

Erlotinib bụ ọgwụ sịntetik edepụtara maka ọgwụgwọ ọrịa kansa. A kwadoro ya ịgwọ ọrịa cancer akwara na-abụghị obere, nnukwu ọrịa cancer prostate metastatic, na maka ọrịa kansa. Nyochaa mmetụta, usoro onunu ogwu, mmekọrịta ọgwụ, ịdọ aka na ntị na ịkpachapụ anya, yana ozi nchekwa afọime tupu ojiji Erlotinib.

 

Reference

[1] Thomas L. Petty, MD (2003). "Nchọpụta nke Azịza Tumor na vlanahụ na Erlotinib na Ndị Ọrịa Na-enweghị Ọrịa Ọrịa Na-adịghị." Akwụkwọ bụ Clinical Oncology. 1 (17): 3–4.

[2] "FDA Na-akwado Roche Ule dị ka CDx maka Tarceva maka Treatgwọ Cerfọdụ Ndị NSCLC Ọrịa". GenomeWeb. Weghachite 10 Jenụwarị 2020.

[3] Dudek AZ, Kmak KL, Koopmeiners J, et al. (2006). "Skin rash na bronchoalveolar histology kwekọrọ na uru ahụike na ndị ọrịa na-emeso gefitinib dị ka ọgwụgwọ maka ọgwụgwọ mbụ ma ọ bụ metastatic nke na-abụghị obere cell cancer cancer". Ọrịa Cancer. 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: Ihe na-akpata insulin-dị ka onye na-anabata ihe ma nweta nguzogide gefitinib (ZD1839; Iressa) na ara mmadụ na mkpụrụ ndụ kansa cancer. Ọrịa Cancer Endocr. 2004 Dec; 11 (4): 793-814.

[5] Kobayashi K, Hagiwara K (2013). "Epidermal na-akpata ihe nnabata ihe nnabata (EGFR) mmụba na ahaziri ọgwụ na elu nonsmall cell lung cancer (NSCLC)". Oncology ezubere iche. 8 (1): 27–33. ma ọ bụ: 10.1007 / s11523-013-0258-9. PMC 3591525. PMID 23361373.

[6] Cohen, Martin H .; Johnson, John R.; Chen, Yeh-Fong; Sridhara, Rajeshwari; Pazdur, Richard (August 2005). "Nchịkọta nkwenye ọgwụ FDA: erlotinib (Tarceva) mbadamba". Onye Oncologist. 10 (7): 461–466.

[7] Blum G, Gazit A, Levitzki A: Mkpụrụ asọmpi asọmpi nke IGF-1 receptor kinase. Mmiri nyocha. 2000 Dec 26; 39 (51): 15705-12.

[8] "Ọgwụ cancer: Courtlọikpe Kasị Elu na-ekwe ka Cipla wepụ arịrịọ megide Roche". Oge akụnụba. 16 June 2017. Edere site na mbụ na 24 Disemba 2019. Weghachite 23 Disemba 2019.

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

[10] Chen X, Ji ZL, Chen YZ: TTD: Usoro Ebumnuche Ọgwụ. Nucleic Acids Nweghachi. 2002 Jenụwarị 1; 30 (1): 412-5.

[11] Filppula AM, Neuvonen PJ, Backman JT: In vitro ntule nke mmetụta na-adabere na oge na CYP2C8 na ọrụ CYP3A site na iri na anọ protein kinase inhibitors. Mwepu Ọgwụ Ọgwụ. 2014 Jul; 42 (7): 1202-9. ma ọ bụ: 10.1124 / dmd.114.057695. Epub 2014 Apr 8.

0 amasị
14068 Echiche

Ị nwere ike na-amasị

Comments na-emechi.