Binciken Dacomitinib Dacomitinib: Yaya Ake Magance NSCLC? - AASraw
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Dacomitinib

 

  1. FDA ta amince da dacomitinib don ƙananan ƙananan ƙwayoyin cuta na huhu
  2. Menene Ciwon ungaramar Cellaramar Namiji?
  3. Aikace-aikacen asibiti na Dacomitinib a cikin ƙananan ƙwayoyin cuta na huhu
  4. Binciken Dacomitinib
  5. Dacomitinib Tsarin aikin
  6. Dacomitinib Yana Amfani
  7. Gurbin Dacomitinib
  8. Maganin Ciwon ungaramar Cellaramar ƙwayar ƙwayar :aramar: Dacomitinib VS Gefitinib
  9. Yadda zaka Sayi Foda Dacomitinib akan layi?

 

FDA ta amince da dacomitinib don ƙananan ƙananan ƙwayoyin cuta na huhu

A ranar 27 ga Satumba, 2018, Hukumar Abinci da Magunguna ta amince da allunan dacomitinib (VIZIMPRO, Kamfanin Magungunan Magunguna na Pfizer) don maganin layin farko na marasa lafiya da cutar metastatic cututtukan daji na kansa marasa kansar (NSCLC) tare da mai karɓar haɓakar haɓakar epidermal (EGFR) exon 19 sharewa ko exon 21 L858R maye gurbin maye gurbi kamar yadda aka gano ta hanyar gwajin FDA.

Amincewa ya dogara ne akan bazuwar, multicenter, bude-lakabin, aiki sarrafawa gwaji (ARCHER 1050; NCT01774721) kwatanta aminci da ingancin dacomitinib zuwa gefitinib a cikin marasa lafiya 452 tare da unresectable, metastatic NSCLC. Ana buƙatar marasa lafiya ba su da magani na farko don cututtukan cututtukan ƙwayar cuta ko maimaita cuta tare da mafi ƙarancin watanni 12 ba tare da cuta ba bayan kammala tsarin ba EGFR TKI mai dauke da magani; matsayin performanceungiyar haɗin gwiwar Onungiyar Gabas ta Tsakiya na 0 ko 1; da EGFR exon 19 sharewa ko exon 21 L858R maye gurbin maye gurbi. An rarraba marasa lafiya (1: 1) don karɓar koyon dacomitinib 45 MG baki ɗaya sau ɗaya a kowace rana ko gefitinib 250 MG da baki sau ɗaya kowace rana har zuwa ci gaban cuta ko cutar da ba za a yarda da ita ba.

Gwajin ya nuna gagarumin ci gaba a rayuwa-ba ta ci gaba; babu ci gaba a cikin ƙimar amsawa gaba ɗaya ko rayuwa gabaɗaya da aka nuna. Rayuwa mara matsakaiciyar ci gaba, kamar yadda kwamitin nazari mai zaman kansa ya ƙaddara. ya kasance watanni 14.7 da 9.2 a cikin dakomitinib da gefitinib makamai, bi da bi (yanayin haɗari 0.59; 95% CI: 0.47, 0.74; p <0.0001).

Bayanin da aka tsara ya ƙunshi gargaɗi da kiyayewa game da cututtukan huhu na ciki (ILD), gudawa, da cututtukan cututtukan fata. Daga cikin marasa lafiya 394 da suka karɓi dacomitinib, munanan halayen mukan faru a cikin 27%. Mafi yawan halayen halayen da suka haifar da dakatarwa a cikin dacomitinib sune gudawa da ILD. Mafi yawan halayen (> 20%) mummunan tasirin dacomitinib sune gudawa, kurji, paronychia, stomatitis, rage ci, bushe fata, rage nauyi, alopecia, tari, da pruritus).

 

Menene Ciwon ungaramar Cellaramar Namiji?

Ciwon daji na huhu shine mafi yawan cutar kansa a duniya, tare da fiye da sababbin mutane miliyan biyu da aka gano a duniya a shekara ta 2018. Kimanin kashi 85 cikin ɗari na dukkanin cututtukan huhu an gano su a matsayin ƙananan ƙwayoyin cuta, kuma kusan kashi 75 cikin ɗari na waɗannan suna metastatic, ko ci gaba, a ganewar asali .

Egfr furotin ne wanda ke taimakawa kwayoyin girma da rarrabuwa. Lokacin da aka canza jigidar EGFR zai iya haifar da furotin ya zama mai aiki sosai wanda hakan zai haifar da kwayar cutar kansa. Canjin EGFR na iya faruwa a 10 zuwa 35 bisa dari na ciwan NSCLC a duniya, kuma maye gurbi mafi yawan aiki shine sharewa a cikin exon 19 da exon 21 L858R maye gurbin, wanda haɗuwa sama da kashi 80 cikin XNUMX na sanannun kunna maye gurbi na EGFR. Cutar tana da alaƙa da ƙananan ƙimar rayuwa da ci gaban cutar har yanzu ƙalubale ne.

AASraw shine ƙwararren masanin kamfanin Dacomitinib.

Da fatan za a danna nan don bayanin zance: Saduwa da mu

 

Aikace-aikacen asibiti na Dacomitinib a cikin ƙananan ƙwayoyin cuta na huhu

Dacomitinib shine ƙarni na biyu na EGFR tyrosine kinase inhibitor (TKI) wanda ba zai yiwu ba ya ɗaure kuma ya hana EGFR / Her1, Her2 da ƙananan subtypes tare da ingancin kwatankwacin sauran TKIs. A cikin gwajin ARCHER 4, rayuwa ta ci gaba ba tare da ci gaba ba ta inganta ta dacomitinib idan aka kwatanta da gefitinib, tallafawa dacomitinib a matsayin zaɓin jiyya na farko don ci gaba da ƙananan ƙwayoyin cuta na ƙananan ƙwayoyin cuta tare da maye gurbin EGFR. Dangane da ƙananan abubuwan da ke faruwa, ragin kashi bai rage tasirin dacomitinib ba kuma zai iya rage tasirin tasirin da tsananin abubuwan da suka faru. Idan aka yi la'akari da yanayin canjin cutar ta EGFR-mutant wanda ba karamar kwayar cutar sankara ba, nan gaba kai tsaye zuwa kwatancen kai tsakanin dacomitinib da osimertinib na iya samar da muhimman bayanai don kayyade jadawalin maganin TKI mafi kyau.

 

Dacomitinib

 

Babban abin da ya haifar da Lananan ungwayar Cutar Sanyi ya tilasta mana yin tunani game da zaɓuɓɓukan magani, ta yaya za a sami ingantattun hanyoyin? Dacomitinib za a bada shawara ga kowa da kowa. Gaba, bari mu duba Dacomitinib:

 

Binciken Dacomitinib

Dacomitinib, an tsara shi azaman (2E) -N-16-4- (piperidin-1-yl) amma-2-enamide, wani yanki ne mai matukar zabi quinazalone na masu hanawa na tyrosine kinase na ƙarni na biyu wanda ke da alaƙa da mawuyacin hali a yankin ATP na haɓakar haɓakar haɓakar haɓakar mahaɗan dangi. Dacomitinib magani ne don maganin ƙananan ƙwayoyin cuta na ƙananan ƙwayoyin cuta (NSCLC). Yana da mai hanawa kuma mai hanawa EGFR.

Dacomitinib ya ci gaba da kamfanin Pfizer Inc kuma FDA ta amince da shi a ranar 27 ga Satumba, 2018. Wasu shaidu a cikin wallafe-wallafen suna ba da shawarar yiwuwar warkewar dacomitinib a cikin samfurin kwayar cutar kanjamau na epithelial, kodayake ana buƙatar ƙarin bincike.

A yanzu, Dacomitinib foda (CAS:1110813-31-4) za a iya bayar da ta AASraw daga China.

 

Dacomitinib Tsarin aikin

Dacomitinib shine mai hana ƙaramar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ɗan adam mai karɓa mai karɓa (EGFR) (EGFR / HER1, HER2, da HER4) tyrosine kinases. Yana samun nasarar hanawa ta hanyar haɗuwa mai haɗuwa zuwa ragowar cysteine ​​a cikin ƙananan yankuna na masu karɓar HER. Dangin dacomitinib an nuna yana da IC50 na 6 nmol / L.

Iyalin ErbB ko epidermal girma factor (EGF) iyali suna taka rawa wajen haɓakar tumo, metastasis, da juriya na jiyya ta hanyar kunna hanyoyin karɓar siginar ƙasa kamar Ras-Raf-MAPK, PLCgamma-PKC-NFkB da PI3K / AKT ta hanyar tyrosine phosphorylation da ke motsa kinase a karboxy-terminus.1 Kusan 40% na shari'oin sun nuna kara kwayar halittar EGFR kuma kashi 50% na shari'ar suna gabatar da maye gurbin EGFRvIII wanda yake wakiltar gogewa wanda ke samar da ci gaba da ci gaba na tyrosine kinase yankin na mai karɓar.

 

Dacomitinib Yana Amfani

An yarda da Dacomitinib don magance: Nonananan ƙananan ƙwayoyin cuta na huhu (NSCLC) wanda ya inganta (yada zuwa wasu sassan jiki). An yi amfani dashi azaman magani na farko a marasa lafiya wanda ciwowar su yana da wasu maye gurbi na EGFR.

Dacomitinib kuma ana nazarin shi a maganin wasu nau'ikan cutar kansa.

 

Gurbin Dacomitinib

Mahimman abubuwa don tunawa game da tasirin dacomitinib:

▪ Mafi yawan mutane ba za su fuskanci duk tasirin tasirin dacomitinib an jera su nan ba.

Effects Abubuwan illa na Dacomitinib galibi ana iya faɗi game da farkon su, tsawon su da kuma tsananin su.

Effects Illolin cutar Dacomitinib zasu inganta bayan an kammala magani.

Effects Dacomitinib sakamakon illa na iya zama mai sauƙin sarrafawa. Akwai zaɓuɓɓuka da yawa don rage ko hana illa na dacomitinib.

AASraw shine ƙwararren masanin kamfanin Dacomitinib.

Da fatan za a danna nan don bayanin zance: Saduwa da mu

 

Wadannan sakamako masu illa na yau da kullun sune (faruwa a cikin fiye da 30%) ga marasa lafiya da ke shan dacomitinib:

Rash Kumburin fata

Infection Cutar ƙwayar ƙusa ko fungal (paronychia)

Skin Fata mai bushewa

▪ Kananan albumin

Calcium Kananan alli

Levels Yawan matakan glucose na jini

Arrhea Gudawa

So Ciwon baki

Ite Rage sha'awa

▪ Anemia (ƙananan haemoglobin)

▪ countaran ƙaran ƙwayoyin jini

Asedara yawan enzymes na hanta

 

Waɗannan ƙananan sakamako ne masu illa (faruwa a cikin 10-29%) ga marasa lafiya masu karɓar dacomitinib:

Pain Ciwon kirji

Som Rashin bacci

Loss Rashin gashi

Yin ƙaiƙayi

▪ Ja, kumburi, da zafi a tafin hannaye da / ko tafin ƙafa

Potassiumarancin potassium, magnesium da sodium

Loss Rage nauyi

▪ Nausa

▪ Maƙarƙashiya

▪ Jin zafi

Pain Ciwon tsoka

Rauni / rashin kuzari

Kumburi ko ciwon ido

▪ serara yawan ƙwayoyin halitta

▪ Tari, alamun hanci da alamominsa, wahalar numfashi da cututtukan fili na sama

Ba duk larurar illa ce aka lissafa a sama ba. Hanyoyin da ke da wuya - suna faruwa a ƙasa da kusan kashi 10 cikin XNUMX na marasa lafiya - ba a lissafa su a nan. Amma koyaushe ya kamata ka sanar da mai ba ka kiwon lafiya idan ka fuskanci wasu alamu na daban.

 

Maganin Ciwon ungaramar Cellaramar ƙwayar ƙwayar :aramar: Dacomitinib VS Gefitinib

Daga cikin marasa lafiya da ke da cutar ta EGFR-tabbatacce, wanda ba shi da ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar cuta (NSCLC), dacomitinib na farko yana inganta rayuwa ba tare da ci gaba ba (PFS) a kan gefitinib, bisa ga binciken 3 na zamani da aka buga a The Lancet Oncology.Dacomitinib

Earnin farko na EGFR-tyrosine kinase inhibitors (TKIs), gami da gefitinib, ana amfani da su a layin farko don marasa lafiya masu cutar EGFR-matsayi, wanda ya kasance tsakanin 10% da 44% na dukkanin huhu adenocarcinomas. Nazarin da ya gabata bai ƙayyade ko ƙarni na biyu EGFR-TKI sun fi na farkon ƙarni iri-iri ba.

Don wannan lakabin bude, binciken da bazuwar (ARCHER 1050; ClinicalTrials.gov Identifier: NCT01774721), wanda marubutan suka lura shine farkon bincike na 3 don kwatanta ƙarni na biyu EGFR-TKI tare da ƙarni na farko EGFR-TKI a cikin wannan saitin , masu bincike sun sanya marasa lafiya 452 don karɓar dacomitinib (227 marasa lafiya) ko gefitinib (225 marasa lafiya). Marasa lafiya tare da metastases na kwakwalwa ba su cancanci ba.

A bin biyan kuɗi na watanni 22.1, PFS na tsakiya ya kasance watanni 14.7 don dacomitinib vs watanni 9.2 don gefitinib; analyididdigar ƙananan ƙungiyoyi kuma sun fi dacewa dacomitinib. An rubuta cikakkun amsoshi goma sha biyu a cikin rukunin dacomitinib vs 4 a cikin kungiyar gefitinib. Responseididdigar amsawar maƙasudin sun kasance, duk da haka, (75% na dacomitinib da 72% don gefitinib; P = .4234).

Marasa lafiya ashirin da ɗaya waɗanda ke karɓar dacomitinib suna da mummunan haɗari da ya shafi mummunan sakamako (AE); wannan gaskiya ne ga marasa lafiya 10 da ke karɓar gefitinib. An bayar da rahoton mutuwar da ke da alaƙa da cutar ga marasa lafiya 2 masu karɓar dacomitinib vs 1 don gefitinib.

Marubutan sun kammala da cewa “maganin dacomitinib ya fi gefitinib game da [PFS] da kuma tsawon lokacin da za a ba da amsa a layin farko na marasa lafiya da cutar EGFR-maye gurbi-tabbatacce NSCLC kuma ya kamata a yi la’akari da sabon zaɓin magani ga wannan yawan. ”

 

Yadda zaka Sayi Foda Dacomitinib akan layi?

Akwai masu yawa / masana'antun furotin dacomitinib a cikin kasuwa, nemo na gaske yana da mahimmanci ga dukkan mutanen da ke buƙatar wannan samfurin cikin gaggawa. Lokacin da muka yanke shawarar siyan foda dacomitinib a kasuwa, muna buƙatar ƙarin koyo game da shi, ku san yadda ake amfani da shi kuma shi ne aikin aiwatarwa, kowane haɗari lokacin da muke shan garin dacomitinib powder. Bugu da kari, farashi da inganci dole ne damuwar mu kafin mu siya.

Bayan mun bincika bayanan daga kasuwa, idan aka kwatanta yawancin masu samarwa, AASraw ya zama kyakkyawan zaɓi ga waɗanda suke son siyan yawancin abubuwa foda dacomitinib, ana sarrafa sarrafa su sosai a ƙarƙashin yanayin cGMP, ana iya sa ido kan ingancin kowane lokaci kuma suna iya samar da duk rahotannin gwaji lokacin da kuke yin oda. Amma game da farashin dacomitinib foda / farashi, yakamata yayi daidai, a idanuna. Saboda na sami farashi da yawa daga masu kawowa daban-daban, idan aka kwatanta da inganci, ina tsammanin aasraw ba zai zama mummunan zaɓi ba.

 

reference

[1] Kobayashi Y, Fujino T, Nishino M, et al. EGFR T790M da C797S maye gurbi a matsayin hanyoyin haɓaka juriya zuwa dacomitinib. J Thorac Oncol. 2018; 13 (5): 727-731. Doi: 10.1016 / j.jtho.2018.01.009.

[2] Kris MG, Camidge DR, Giaccone G, et al. Target aberrations HER2 kamar yadda direbobi masu aiki a cikin cututtukan huhu: lokaci na II na gwaji na pan-HER tyrosine kinase inhibitor dacomitinib a cikin marasa lafiya tare da HER2-mutant ko ƙari ƙari. Ann Oncol. 2015; 26 (7): 1421-1427. Doi: 10.1093 / annonc / mdv383.

[3] Park K, Tan EH, O'Byrne K, et al. Afatinib da gefitinib a matsayin maganin farko na marasa lafiya tare da maye gurbi na EGFR-tabbatacce ba ƙaramin kwayar cutar huhu ba (LUX-Lung 7): lokaci na 2B, lakabin buɗewa, gwajin gwajin bazuwar. Lancet Oncol. 2016; 17 (5): 577-589. Doi: 10.1016 / S1470-2045 (16) 30033-X.

[4] Lacouture ME, Keefe DM, Sonis S, et al. Nazarin lokaci na II (ARCHER 1042) don kimanta maganin prophylactic na dacomitinib wanda ya haifar da cututtukan fata da cututtukan ciki a cikin ciwon daji na ƙananan ƙwayoyin cuta. Ann Oncol. 2016; 27 (9): 1712-1718. Doi: 10.1093 / annonc / mdw227.

[5] Reckamp KL, Giaccone G, Kamarar DR, et al. Gwajin 2 na lokaci na dacomitinib (PF ‐ 00299804), mai hanawa, mai hanawa pan HER (mai karɓar haɓakar haɓakar ɗan adam epidermal) mai hanawa, a cikin marasa lafiya da ke fama da cutar kansar huhu mai ƙaramar ƙwayar cuta bayan gazawar chemotherapy da erlotinib. Ciwon daji. 2014; 120 (8): 1145-1154. Doi: 10.1002 / cncr.28561.

[6] Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET haɓakawa yana haifar da juriya gefitinib a cikin cutar sankarar huhu ta kunna siginar ERBB3. Kimiyya. 2007; 316 (5827): 1039-1043. Doi: 10.1126 / kimiyya.1141478.

[7] Liu X, Wang P, Zhang C, et al. Mai karɓar haɓakar haɓakar Epidermal (EGFR): Tauraruwa mai tasowa a zamanin da ya dace da maganin kansar huhu. Oncotarget. 2017; 8 (30): 50209-50220.

[8] Girard N. Inganta sakamako a cikin EGFR maye gurbi-tabbatacce NSCLC: wace tyrosine kinase inhibitor kuma yaushe? Future Oncol 2018.

[9] Inoue A, Kobayashi K, Maemondo M, et al. Sakamakon ƙarshe na ƙarshe na NEJ002, gwajin lokaci na III wanda aka kwatanta gefitinib zuwa carboplatin (CBDCA) tare da paclitaxel (TXL) azaman farkon layin farko don ƙananan ƙwayoyin cuta na ƙananan ƙwayoyin cuta (NSCLC) tare da maye gurbin EGFR. J Jarin Oncol 2011; 29: 7519.

[10] Sequist LV, Yang JC, Yamamoto N, et al. Karatun III na afatinib ko cisplatin tare da haɗuwa a cikin marasa lafiya tare da cututtukan huhu adenocarcinoma tare da maye gurbin EGFR. J Jarin Oncol 2013; 31: 3327-34.

[11] Lin JJ, Cardarella S, Lydon CA, et al. Rayuwa ta Shekaru Biyar a cikin EGFR-Mutant Metastatic Lung Adenocarcinoma Wanda aka Kula dashi tare da EGFR-TKIs. J Thorac Oncol 2016; 11: 556-65.

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