Waa maxay macluumaadka ay tahay inaad ogaato kahor intaadan isticmaalin Erlotinib - AASraw
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Erlotinib

 

  1. Waa maxay Erlotinib?
  2. Sidee Erlotinib u shaqeeyaa?
  3. Cudurro Maxay Erlotinib Si Weyn U Daweeyaan?
  4. Sidee Erlotinib hada loogu adeegsadaa bukaan socod eegtada?
  5. Bukaankee Ayuu Erlotinib Ugu Waxtar Badan Yahay?
  6. Waa maxay Cadaadiska Erlotinib?
  7. Maxay Khataraha La Xiriirinayaan Erlotinib?
  8. Waa Kuwee Daawooyinka ama Kaabisyada Dhexgalka Ah ee Erlotinib?
  9. FDA Ansixisay Daaweynta Erlotinib
  10. Summary

 

Waa maxay Erlotinib

Erlotinib (CAS:183321-74-6) wuxuu ka tirsan yahay nooc daroogo ah oo loo yaqaan 'tyrosine kinase inhibitors'. Waxay ku shaqeysaa iyadoo la xirayo shaqada borotiinka loo yaqaan 'epidermal growth factor receptor' (EGFR). EGFR waxaa laga helaa dusha sare ee unugyada kansarka iyo sidoo kale unugyada caadiga ah. Waxay u adeegtaa sidii "anteeno," iyadoo ka heleysa calaamadaha unugyada kale iyo bay'ada u sheegaysa unugga inuu koro oo uu qaybsamo. EGFR wuxuu door muhiim ah ka ciyaaraa koritaanka iyo horumarka dhalmada ka hor iyo inta lagu jiro carruurnimada waxayna ka caawisaa sidii loo ilaalin lahaa beddelka caadiga ah ee unugyada gaboobay iyo kuwa dhaawacmay ee dadka waaweyn. Si kastaba ha noqotee, unugyo badan oo kansar ah waxay leeyihiin xaddi badan oo aan caadi ahayn oo ah EGFR dusha sare, ama EGFR-kooda waxaa lagu beddelay isbeddel ku yimid DNA oo xambaarsan koodhka hidda-wadaha ee borotiinka. Natiijadu waxay tahay in calaamadaha ka imanaya EGFR ay aad u xoog badan yihiin, taas oo horseedaysa koritaanka unugyada iyo kala qaybsanaanta, astaamaha kansarka.

 

Sidee Erlotinib Shaqo? 

Farsamaynta ficil-celinta antitumor-ka ee erlotinib si buuxda uma sifoobo. Erlotinib wuxuu xakameynayaa fosforyaalka ilmo galeenka ee tyrosine kinase ee laxiriira Calaamadaha koritaan ee epidermal (EGFR). Khaaska ah ka-hortagga marka loo eego kuwa kale ee tyrosine kinase reseptors si buuxda looma aqoonsan. EGFR waxaa lagu muujiyey dusha sare ee unugyada unugyada caadiga ah iyo unugyada kansarka.

 

Waxa Cudurradu qabtaan Erlotinib Badanaa Daaweynta? 

(1) Kansarka sanbabada

Erlotinib oo kujira kansarka sanbabada ee unugyada aan yareyn ee aan lakala saari karin markii lagu daro kemotherabi wuxuu wanaajiyaa guud ahaan badbaadada 19%, iyo wanaajinta badbaadada horumarka bilaashka ah (PFS) ee 29%, marka la barbardhigo kemoterapi oo keliya. Maamulka Cuntada iyo Dawooyinka ee Mareykanka (FDA) ayaa ogolaaday erlotinib loogu talagalay daaweynta kansarka sanbabada ee unugyada unugyada yar-yar ama heer-ka-hooseeya ah ee ku guuldareystay ugu yaraan hal nidaam hore oo daaweynta kiimikada ah.

Cudurka kansarka sanbabada, erlotinib waxaa loo muujiyey inuu waxtar u leeyahay bukaanada qaba ama aan laheyn isbedelada EGFR, laakiin wuxuu umuuqdaa inuu waxtar badan u leeyahay bukaanada qaba isbeddelada EGFR. Nolosha guud, badbaadada horusocodka la'aan iyo halsano halsano ah waxay lamid tahay heerka labaad daaweynta (docetaxel ama pemetrexed). Qiyaasta guud ee jawaabta waxay qiyaastii 50% kafiicantahay heerka labaad ee kimikalka. Bukaanka aan sigaarka cabbin, iyo kuwa caba sigaar cabayaashii hore, adenocarcinoma ama noocyo hoosaadyo ah sida BAC waxay u badan tahay inay yeeshaan isbadalada EGFR, laakiin isbadalku wuxuu ku dhici karaa dhamaan noocyada bukaanada . Tijaabad ku saabsan isbeddelka EGFR waxaa soo saaray Genzyme.

 

(2) Kansarka Pankreatic

Bishii Nofeembar 2005, FDA waxay oggolaatay erlotinib oo ay weheliso gemcitabine si loogu daaweeyo kansarka xannuunka maxalliga ah ee horumarsan, aan la xakamayn karin, ama metastatic.

AASraw waa soo saaraha xirfadlaha ah ee Erlotinib.

Fadlan halkan guji si aad u hesho macluumaadka xigashada: Nala soo xiriir

 

(3) Diidmada daaweynta

Erlotinib wuxuu ku xidhan yahay ErbB1 marka la eego xalka 2.6A; Midabka dusha sare ayaa muujinaya hydrophobicity.Sida ATP-yada kale ee loo yaqaan 'molecule tyrosine kinase inhibitors' yar yar ee tartamaya, sida imatinib ee CML, bukaanku si dhakhso leh ayey u yeeshaan iska caabin. Xaalada erlotinib tani caadi ahaan waxay dhacdaa 8-12 bilood laga bilaabo bilowga daaweynta. In ka badan 50% ee iska caabinta waxaa sababa isbeddel ku yimaada jeebka ATP ee ku xiran EGFR kinase domain oo ku lug leh beddelista hadhaaga yar ee polar threonine oo leh haraaga weyn ee nonhlar methionine (T790M) .Qiyaas ahaan 20% ee caabbinta daroogada waxaa sababa kordhinta hepatocyte factor factor receptor, kaas oo wada ERBB3 firfircoonaanta firfircoonaanta PI3K.

 

Erlotinib

 

Sidee Is Erlotinib Cmarmar Used In The Clinic?

Erlotinib waxaa markii ugu horeysay ansixiyay Maamulka Cuntada iyo Dawooyinka ee Mareykanka (FDA) si loogu isticmaalo bukaanada qaba kansarka sanbabada ee unugyada aan yareyn oo soo noq noqday ka dib ugu yaraan hal nooc oo daaweyn ah. Sannadkii 2005, waxaa loo oggolaaday in lagu daro daawo kale, gemcitabine, oo loogu talagalay kansarka xannuunsan ee horumarsan. Sannadkii 2010, isticmaalkiisa waxaa loo ballaariyay in lagu daro daaweynta dayactirka ee bukaannada qaba kansarka sanbabada ee unugyada aan yareyn oo cudurkoodu uu xasilloon yahay ka dib afar wareeg oo daaweyn ah oo lagu daweeyay dawada ku saleysan platina, sida cisplatin ama karboplatin. Bukaannada qaata erlotinib badanaa waxay u dulqaataan daroogada si aad u wanaagsan. Saameynaha ugu caansan waa firiiric maqaarka ah iyo shuban biyood.

 

In Wtaas Piyo Is Erlotinib MOST Ewaxtar leh?

Tobankii sano ee la soo dhaafey, daaweeyayaashu waxay khibrad aad u weyn ka heleen la tacaaliyeyaasha tyrosine kinase, sida erlotinib, oo xannibaya EGFR. Waxaa si isa soo taraysa u cadaatay in dawooyinkani ay sida ugu fiican ugu shaqeeyaan bukaanada kuwaas oo kansarka sanbabada wuxuu xambaarsan yahay nooc isbeddel gaar ah oo keena borotiin aan caadi ahayn oo EGFR ah. Bukaanadani waxay u badan tahay inay ka soo jeedaan Aasiya, haween, weligoodna aan sigaar cabbin oo qaba nooc ka mid ah kansarka sambabka ee loo yaqaan 'bronchoalveolar adenocarcinoma'. Sidaa darteed, 2013, erlotinib waxaa loo oggolaaday inuu noqdo daaweynta ugu horreysa ee koox-hoosaadkan bukaan-socodka ah, haddii kansarkooda aan lagu daaweyn karin qalliin.

 

Waa maxay Is Erlotinib Rtaageero?

Erlotinib wuxuu si aad ah waxtar ugu leeyahay hoosaadka bukaanada qaba isbeddelada EGFR. Si kastaba ha noqotee, xitaa bukaannadan ayaa ugu dambeyntii bilaabi doona inay muujiyaan horumarka kansarkooda ka dib qiyaastii 12 bilood ee daaweynta erlotinib. Tani waxay sabab u tahay horumarka caabbinta daawada ee unugyada kansarka haraaga. Xaalado badan, caabbinta waxay ka dhalataa horumarinta isbeddel labaad ee borotiinka EGFR ee ka hortagaya erlotinib inuu ku xirnaado cinwaanka tyrosine kinase. Hababka cusub ee lagu daaweynayo bukaannadan waxaa ka mid ah dhowaan soo-saare tyrosine kinase inhibitor afatinib, keligiis ama lagu daro cetuximab (Erbitux), oo xakameynaya EGFR iyada oo loo adeegsanayo farsamo ka duwan.

 

Maxay Khataraha La Xiriirinayaan Erlotinib?

Daraasadaha, waxyeelooyinka ugu badan ee ka yimaada Erlotinib markii loo isticmaalay daaweynta monotherapy ee kansarka sanbabada waxay ahaayeen finan (saameyn ku yeeshay 75% bukaannada), shuban (54%), rabitaanka cuntada iyo daal (52% midkiiba). Daraasada Tarceva ee loo isticmaalo gemcitabine ee kansarka ganaca, waxyeelada ugu badan waxay ahayd daal (saameyn ku yeelatay 73% bukaanka), finan (69%) iyo shuban (48%). Liiska buuxa ee dhibaatooyinka soo raaca iyo xaddidaadda Erlotinib, fiiri buug-yaraha xirmada.

 

Waa kuwee Droogaga ama Shagaajinta Idareemo Wimp Erlotinib?

CYP3A4 waa enzyme ku jira beerka oo burbura isla markaana ka caawiya ka takhalusida erlotinib jirka. Daawooyinka xakameynaya CYP3A4 waxay sababi karaan heerar sare ee erlotinib ee jirka, heerarka sarena waxay sababi karaan sunta ka timaada erlotinib. Daawooyinka noocan ah waxaa ka mid ah atazanavir (Reyataz), clarithromycin (Biaxin), indinavir (Crixivan), itraconazole (Sporanox), ketoconazole (Nizoral), nefazodone (Serzone), nelfinavir (Viracept), ritonavir (Norvir), sainav; telithromycin (Ketek), iyo voriconazole (VFEND). Bukaannada qaata daawooyinkan, qadar yar oo ah erlotinib ayaa loo baahan karaa si looga hortago sunta.

Daawooyinka qaarkood waxay kordhiyaan baabi'inta erlotinib iyagoo kordhinaya waxqabadka enzymes-ka 'CYP3A4'. Tani waxay yareysaa heerarka erlotinib ee jirka waxayna yareyn kartaa saameyntiisa. Daawooyinka noocaan ah waxaa kamid ah rifampicin (Rifadin), rifabutin (Mycobutin), rifapentine (Priftin), phenytoin (Dilantin), carbamazepine (Tegretol), phenobarbital iyo St. John's Wort. Daawooyinkan waa in laga fogaadaa bukaannada qaata erlotinib, haddii ay suurogal tahay. Haddii daawooyinka kale aysan ikhtiyaar u ahayn, qiyaaso badan oo ah erlotinib ayaa loo baahan karaa. Sigaarka sigaarku wuxuu kaloo yareeyaa isku-darka erlotinib ee dhiiga. Bukaanka waxaa lagula talinayaa inay joojiyaan sigaar cabista.

Daawooyinka yareeya soo saarista aashitada ee caloosha ayaa yareyn doonta nuugista erlotinib. Sidaa darteed, proton pump inhibitors (PPI's, tusaale ahaan, omeprazole [Prilosec, Zegerid]) waa inaan lagu maamulin erlotinib, erlotinibna waa in la qaataa 10 saacadood kahor H2-receptor blockers (tusaale ahaan, ranitidine [Zantac]) ama laba saacadood kadib qaadashada xannibaadaha H2-receptor.

Maamulka dawooyinka antacids waa in laga soocaa maamulka erlotinib dhawr saacadood. Erlotinib waxaa lala xiriiriyay halista sii kordheysa ee dhiigbaxa, gaar ahaan bukaanada sidoo kale qaata warfarin (Coumadin). Bukaanka qaata warfarin waa in si dhaw loola socdaa.

 

FDA ayaa la ansixiyey Erlotinib Daaweynta

Bishii Oktoobar 18, 2016, Maamulka Cuntada iyo Dawooyinka ee Mareykanka ayaa wax ka beddelay tilmaanta erlotinib (TARCEVA, Astellas Pharm Global Development Inc.) ee daaweynta kansarka sanbabada ee unugyada yaryar (NSCLC) si loo xaddido isticmaalka bukaannada burooyinkoodu ay leeyihiin isbeddello isbeddel qaata ah oo loo yaqaan 'epidermal growth factor receptor' (EGFR)).

Isbedelka calaamadeynta wuxuu quseeyaa bukaanada qaba NSCLC ee hela dayactirka ama daaweynta khadka labaad ama ka weyn. Tilmaamahan ayaa ku koobnaan doona bukaanada burooyinka burooyinkoodu leeyihiin EGFR exon 19 tirtirid ama ay dhaafaan 21 L858R beddelaadyada beddelka ah sida lagu ogaaday baaritaanka ay ansixisay FDA. Tilmaanta hore ee xariiqda hore waxay ku xaddidnayd bukaanada qaba EGFR exon 19 tirtir ama exon 21 beddelid beddelaad ah.

Kordhinta calaamaddan waxay ku saleysan tahay natiijooyinka tijaabada IUNO, kala-sooc, indho-indhoole, xakamaynta xakamaynta, tijaabinta erlotinib oo loo bixiyo daaweynta dayactirka ee 643 bukaan ah oo leh heer sare oo NSCLC ah oo aan horay u soo marin cudurka ama sun aan la aqbali karin intii lagu jiray afar wareeg oo daaweynta kiimiko ee safka hore ee ku saleysan platina Bukaannada burooyinka ay leeyihiin firfircoonaanta isbeddelka EGFR (exon 19 tirtir ama exon 21 L858R mutations) ayaa laga reebay tijaabadan. Bukaannada waxaa loo kala soocay 1: 1 si ay u helaan erlotinib ama placebo hadal ahaan hal mar maalintii (322 erlotinib, 321 placebo) illaa cudurka uu ka sii socdo ama sun aan la aqbali karin. Ka dib markii la sii waday daaweynta bilowga ah, bukaanku waxay xaq u yeesheen inay galaan marxalad calaamadeysan oo furan. Boqolkiiba konton bukaanada loo qoondeeyay erlotinib waxay galeen wajiga calaamada furan waxayna heleen daweynta kiimoteraabiga ah, halka 77% bukaanada loo kala saaray placebo ay galeen wajiga calaamada furan waxayna heleen erlotinib.

Dhamaadka ugu dambeeya ee maxkamadaynta ayaa ahayd badbaado guud. Natiijooyinka waxay muujiyeen in badbaadada ka dib daaweynta erlotinib aysan ka fiicneyn placebo oo loo maamuley dayactirka bukaanada qaba burooyinka NSCLC ee metatatic ah ee aan ku xirneyn isbeddellada EGFR. Ma jiro farqi u dhexeeya badbaadada horumarka-ka-madax-bannaan ee u dhexeeya cududda erlotinib iyo gacanta xuubka dhagaha ayaa la arkay.

FDA uma baahna shuruudaha cusub ee suuq-geynta ka dib ama ma codsan doonto ballan-qaadyada suuq-geynta kadib oo ku saleysan natiijooyinka tijaabada IUNO.

AASraw waa soo saaraha xirfadlaha ah ee Erlotinib.

Fadlan halkan guji si aad u hesho macluumaadka xigashada: Nala soo xiriir

 

Summary

Erlotinib waa dawo synthetic loo qoro si loogu daweeyo kansarka. Waxaa loo oggol yahay in lagu daaweeyo kansarka sanbabada ee unugyada aan yareyn, kansarka qanjirka 'prostate cancer' ee aan latareyn karin, iyo kansarka ganaca. Dib u eeg waxyeellooyinka, qiyaasta, isdhexgalka daroogada, digniinta iyo taxaddarrada, iyo macluumaadka badbaadada uurka kahor isticmaalka Erlotinib.

 

Tixraaca

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[2] "FDA Waxay Ansixineysaa Baaritaanka Roche oo ah CDx loogu talagalay Tarceva ee lagu daaweynayo Bukaannada NSCLC qaarkood". GenomeWeb. Raadin 10 Janaayo 2020.

[3] Dudek AZ, Kmak KL, Koopmeiners J, iyo al. (2006). "Furuq-furka maqaarka iyo cilladda 'bronchoalveolar histology' waxay la xiriirtaa faa iidada bukaan-socodka ee bukaanada lagu daweeyay gefitinib oo ah daaweyn horay loogu daweeyay kansarka sanbabada ee unugyada aan sii yarayn '. Kansarka Sambabka. 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: Calaamadaha koritaanka insulin-u eg ee calaamadaha i-qaadashada iyo helitaanka iska caabbinta gefitinib (ZD1839; Iressa) ee naasaha aadanaha iyo unugyada kansarka qanjirka 'prostate'. Kansarka Cudurka Endocr Relat. 2004 Dec; 11 (4): 793-814.

[5] Kobayashi K, Hagiwara K (2013). "Isbeddelka Epidermal factor factor receptor (EGFR) isbeddellada iyo daaweynta shakhsi ahaaneed ee kansarka sanbabada ee unugyada aan caadiga ahayn (NSCLC)". Onkolojiyada Bartilmaameedka ah. 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 (Ogosto 2005). "Koobida oggolaanshaha daroogada ee FDA: kiniinnada erlotinib (Tarceva)". Dhakhtarka Oncologist. 10 (7): 461–466.

[7] Blum G, Gazit A, Levitzki A: Substrate tartameyaasha ka hortagga ee IGF-1 reseptor kinase. Bayoolaji. 2000 Diis 26; 39 (51): 15705-12.

[8] "Daroogada Kansarka: Maxkamadda Sare waxay u oggolaaneysaa Cipla inay ka noqoto rafcaanka ka dhanka ah Roche". Waqtiyada Dhaqaalaha. 16 Juunyo 2017. Waxaa laga keydiyay asalka 24-kii Diseembar 2019. Waxaa laga soo xigtay 23 Diseembar 2019.

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

[10] Chen X, Ji ZL, Chen YZ: TTD: Macluumaadka Bartilmaameedka Daaweynta. Nucleic Acids Res. 2002 Janaayo 1; 30 (1): 412-5.

[11] Filppula AM, Neuvonen PJ, Backman JT: Qiimaynta ficil-celinta ee saameynta xannibaadda waqtiga-ku-tiirsan ee CYP2C8 iyo waxqabadka CYP3A ee afar iyo toban kahortagayaasha kinase protein. Daroogada Metab. 2014 Jul; 42 (7): 1202-9. doi: 10.1124 / dmd.114.057695. Epub 2014 Apr 8.

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