Dacomitinib Dacomitinib Ongororo: Maitiro Ekurapa NSCLC? -AASraw
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Dacominib

 

  1. FDA inobvumidza dacomitinib ye metastatic isiri-diki kenza yemapapu kenza
  2. Chii chinonzi Non-Mudiki Cell Lung Cancer?
  3. Dacomitinib kiriniki yekushandisa mune isiri-diki-sero kenza yemapapu
  4. Ongororo yeDacomitinib
  5. Dacomitinib Maitiro ekuita
  6. Dacomitinib Anoshandisa
  7. Dacomitinib Side Mhedzisiro
  8. Isiri-diki Cell Lung Cancer Kurapa: Dacomitinib VS Gefitinib
  9. Maitiro Ekutenga Dacomitinib Powder pamhepo?

 

FDA inobvumidza dacomitinib ye metastatic isiri-diki kenza yemapapu kenza

Musi waSeptember 27, 2018, Chikafu neDrug Administration chakabvumidza mapiritsi e dacomitinib (VIZIMPRO, Pfizer Pharmaceutical Company) yekurapa kwekutanga kwevarwere vane metastatic. isina-diki kenza yemapapu kenza (NSCLC) ine epidermal grow factor receptor (EGFR) exon 19 kubviswa kana exon 21 L858R inoshandura shanduko sezvinoonekwa nemuedzo unobvumidzwa neDFA.

Kubvumidzwa kwaive kwakavakirwa pane yakasarudzika, multicenter, yakavhurika-label, inoshanda inodzorwa kutongwa (ARCHER 1050; NCT01774721) achifananidza kuchengetedzeka uye kushanda kwe dacomitinib kune gefitinib mune 452 varwere vane unresectable, metastatic NSCLC. Varwere vaifanirwa kunge vasina kurapwa kwekutanga kwechirwere chemasastatic kana chirwere chinodzokororwa chine hushoma hwemwedzi gumi nembiri husina chirwere mushure mekupedza systemic isiri-EGFR TKI-ine kurapa; yeEastern Cooperative Oncology Boka mamiriro e12 kana 0; uye EGFR exon 1 kubvisa kana exon 19 L21R kutsiva shanduko. Varwere vaisarudzika (858: 1) kuti vagamuchire kana dacomitinib 1 mg muromo kamwe chete zuva nezuva kana gefitinib 45 mg muromo kamwe chete zuva nezuva kudzamara hosha ichiwedzera kana huturu husingagamuchirike.

Iko kutongwa kwakaratidza kuwedzera kukuru mukufambira mberi-kwemahara kupona; hapana kuvandudzwa kwehuwandu hwekupindura kana kupona kwese kwakaratidzwa. Iyo yepakati yekufambira mberi-yemahara kupona, sekumisikidzwa nedare rakazvimirira rekuongorora. yaive 14.7 uye 9.2 mwedzi mune iyo dacomitinib uye gefitinib maoko, zvichiteerana (hazard ratio 0.59; 95% CI: 0.47, 0.74; p <0.0001).

Ruzivo rwekutsvagisa rune yambiro uye chenjedzo yehutachiona hwepapu (ILD), manyoka, uye dermatologic maitiro akashata. Pakati pevarwere makumi mana nevana vakagamuchira dacomitinib, kukanganiswa kwakakomba kwakaitika mu394%. Mhedzisiro inowanzoitika yakaipa inokonzeresa kuregedza kweiyo dacomitinib yaive manyoka uye ILD. Iwo akajairika (> 27%) maitiro akashata e dacomitinib yaive manyoka, mapundu, paronychia, stomatitis, kuderera kwekuda kudya, ganda rakaoma, huremu hwakaderera, alopecia, chikosoro, uye pruritus).

 

Chii chinonzi Non-Mudiki Cell Lung Cancer?

Kenza yemapapu ndiyo kenza yakajairika pasi rese, iine anopfuura mamirioni maviri mitsva mitsva inowanikwa pasi rose muna 2018. Inenge 85 muzana yemakenza ese emapapu anoonekwa seasina-diki sero, uye ingangoita 75 muzana yeawo metastatic, kana yepamusoro, pakuongororwa. .

Egfr puroteni inobatsira maseru kukura uye kupatsanuka. Kana iyo EGFR geni ikashandurwa inogona kukonzera kuti puroteni ive yakanyanyisa kukonzeresa kuti maseru ekenza aumbe. EGFR shanduko dzinogona kuitika mu10 kusvika 35 muzana yematumbu eNSCLC pasi rese, uye shanduko dzinowanzoitika dzinobvisa mu exon 19 uye exon 21 L858R kutsiva, izvo pamwe chete zvinomiririra zvinopfuura makumi masere muzana ezita rinozivikanwa rinoshandura shanduko yeEGFR. Chirwere ichi chinosanganisirwa neakaderera kupona kwehuwandu uye kuwedzera kwechirwere kunoramba kuri dambudziko.

AASraw ndiye nyanzvi yekugadzira Dacomitinib.

Ndokumbirawo ubaye pano kuti uwane ruzivo Cont Cont us

 

Dacomitinib kiriniki yekushandisa mune isiri-diki-sero kenza yemapapu

Dacomitinib chizvarwa chechipiri EGFR tyrosine kinase inhibitor (TKI) iyo isingadzoreke kusunga uye inodzivirira EGFR / Her1, Her2 uye Her4 subtypes ine hunyanzvi hwakaenzana nemamwe maTKI. Mune iyo ARCHER 1050 kuyedza, kufambira mberi-kwemahara kuponeswa kwakagadziriswa ne dacomitinib kana ichienzaniswa ne gefitinib, ichitsigira dacomitinib seyekutanga-yekurapa sarudzo yekenza yepamberi isiri-diki-kenza yemapapu ine shanduko yeEGFR. Nezve kune yakakwira yakashata zviitiko mwero, kudzikiswa kwedosi hakuna kudzikisa kushanda kwe dacomitinib uye kunogona kudzikisira zvakanyanya kuitika uye kuomarara kwezviitiko zvakashata. Tichifunga nezvekushanduka kwenzvimbo yeEGFR-mutant isiri-diki-kenza yemapapu kenza, ramangwana musoro kumusoro kuenzanisa pakati pe dacomitinib na osimertinib inogona kupa ruzivo rwakakosha kuti rione rakaringana TKI kurapwa chirongwa.

 

Dacominib

 

Kuwanda kwakanyanya kweiyo Isiri-Diki Cell Lung Cancer yakamanikidza isu kufunga nezvesarudzo nzira dzekurapa, nzira dzekuwana nzira dzinoshanda. Dacominib kurapwa kuchakurudzirwa kune wese munhu. Tevere, ngatitarisei Dacominib:

 

Ongororo yeDacomitinib

Dacomitinib, yakagadzirirwa se (2E) -N-16-4- (piperidin-1-yl) asi-2-enamide, inotaurwa inonyatsosarudza quinazalone chikamu chechipiri-chizvarwa tyrosine kinase inhibitors iyo inozivikanwa nekusadzoreka kusunga pa iyo ATP dhata yeiyo epidermal yekukura factor receptor mhuri kinase domains. Dacomitinib imishonga yekurapa isiri-diki-cell lung carcinoma (NSCLC). Iyo inosarudza uye isingadzoreke inhibitor yeEGFR.

Dacomitinib yakagadzirwa naPfizer Inc uye yakatenderwa neFDA musi waGunyana 27, 2018. Humwe humbowo muzvinyorwa hunoratidza kugona kwekurapa kwa dacomitinib mune epithelial ovarian kenza modhi, kunyangwe kumwe kuongorora kuri kudikanwa.

Parizvino, Dacomitinib powder (CAS:1110813-31-4) inogona kupihwa neAASraw kubva kuChina.

 

Dacomitinib Maitiro ekuita

Dacomitinib isingachinjiki diki mamorekuru inhibitor yechiitiko chevanhu epidermal kukura factor receptor (EGFR) mhuri (EGFR / HER1, HER2, uye HER4) tyrosine kinases. Inoita zvisingadzoreke kuvharika kuburikidza ne covalent bonding kune iyo cysteine ​​masara munzvimbo dzinobatsira dze HER receptors. Hukama hwe dacomitinib hwakaratidzirwa kuve iine IC50 ye6 nmol / L.

Iyo ErbB kana Epidermal kukura chinhu (EGF) mhuri inoita chinzvimbo mukukura kwechipfuva, metastasis, uye kurapwa kurapa nekumisikidza yakadzika nzira yekushambadzira nzira senge dzakadai saRas-Raf-MAPK, PLCgamma-PKC-NFkB uye PI3K / AKT kuburikidza neiyo tyrosine kinase-inotyairwa phosphorylation pa carboxy-terminus.1 Around 40% yematambudziko anoratidza kukwidziridzwa kweEGFR geni uye 50% yematambudziko aripo EGFRvIII mutation inomiririra kubviswa kunounza kuenderera kumisikidza kweiyo tyrosine kinase domain yeiyo receptor.

 

Dacomitinib Anoshandisa

Dacomitinib inobvumidzwa kurapa: Isiri-diki kenza kenza yemapapu (NSCLC) ine metastasized (yakapararira kune zvimwe zvikamu zvemuviri). Iyo inoshandiswa sekutanga-mutsara kurapwa mune varwere vane mamota ane mamwe EGFR magene ekuchinja.

Dacomitinib iri kudzidziswawo mukurapwa kwemamwe marudzi ekenza.

 

Dacomitinib Side Mhedzisiro

Zvinhu zvakakosha zvekurangarira nezve mhedzisiro yemhedzisiro yedacomitinib:

▪ Vanhu vazhinji havazowani zvese zve dacomitinib mhedzisiro dzakanyorwa pano.

▪ Dacomitinib mhedzisiro inowanzo fungidzirwa maererano nekutanga kwavo, nguva uye kuomarara.

▪ Dacomitinib mhedzisiro ichavandudza mushure mekurapwa kwapera.

▪ Dacomitinib mhedzisiro inogona kunge ichikwanisika. Pane zvakawanda zvingasarudzika kudzikisira kana kudzivirira mhedzisiro yemhedzisiro yedacomitinib.

AASraw ndiye nyanzvi yekugadzira Dacomitinib.

Ndokumbirawo ubaye pano kuti uwane ruzivo Cont Cont us

 

Iyi inotevera mhedzisiro yakajairika (inoitika mune yakakura kupfuura 30%) yevarwere vanotora dacomitinib:

▪ Mapundu eganda

▪ Utachiona hwenzara kana fungal (paronychia)

▪ Ganda rakaoma

▪ Low albumin

▪ Yakaderera calcium

▪ Yakakwira shuga yeropa

▪ Manyoka

▪ Maronda emumuromo

▪ Kuderedza kudya

▪ Anemia (yakaderera hemoglobin)

▪ Yakaderera masero eropa machena

▪ Kuwedzera enzyme yechiropa

 

Aya mashoma mhedzisiro mhedzisiro (inoitika mu10-29%) yevarwere vanogamuchira dacomitinib:

▪ Kurwadziwa pachipfuva

▪ Kushaya hope

▪ Kurasikirwa nebvudzi

▪ Kuvava

▪ Kutsvuka, kuzvimba, uye kurwadziwa muzvanza zvemaoko uye / kana pasi petsoka

▪ Low potasium, magnesium uye sodium mwero

▪ Kuonda

▪ Nausea

▪ Kuzvimbirwa

▪ Marwadzo emakumbo

▪ Kurwadziwa kwemhasuru

▪ Kushaya simba / kushaya simba

▪ Kuzvimba kana hutachiona hwemaziso

▪ Yakawedzera serum creatinine

▪ Kukosora, zviratidzo zvemumhino nezviratidzo, kunetseka kufema uye hutachiona hwepamusoro hwekufema

Haasi ese mhedzisiro akanyorwa pamusoro. Mhedzisiro mhedzisiro isingawanzo - inoitika mune isingasviki gumi muzana yevarwere - haina kunyorwa pano. Asi iwe unofanirwa kugara uchizivisa mupi wako wezvehutano kana iwe uchinge uchinge uchinge uchinge uchinge uchinge uchinge uchinge uchinge uchinge uchiona zviratidzo

 

Isiri-diki Cell Lung Cancer Kurapa: Dacomitinib VS Gefitinib

Pakati pevarwere vane EGFR-yakanaka, isiri- huro metastatic isiri-diki kenza yemapapu kenza (NSCLC), yekutanga-mutsara dacomitinib inovandudza kufambira mberi-kusununguka kupona (PFS) pamusoro pegefitinib, sekureva kwechikamu chechitatu kudzidza kwakaburitswa muThe Lancet Oncology.Dacominib

Chizvarwa chekutanga EGFR-tyrosine kinase inhibitors (TKIs), kusanganisira gefitinib, inoshandiswa mumutsara wekutanga wevarwere vane EGFR-chinzvimbo chirwere, icho chinoumba pakati pe10% ne44% yemapapu adenocarcinomas ese. Ongororo yapfuura haina kusarudza kana chechipiri-chizvarwa EGFR-TKIs chakakwirira kune yekutanga-chizvarwa dzakasiyana.

Kune iri rakavhurika-rekodhi, kudzidza kwakasarudzika (ARCHER 1050; ClinicalTrials.gov Chitupa: NCT01774721), iyo yakanyorwa nevanyori ndiyo yekutanga chikamu 3 kudzidza kuenzanisa yechipiri-chizvarwa EGFR-TKI neyekutanga-chizvarwa EGFR-TKI mune ino mamiriro , vatsvagiri vakanyoresa varwere ve452 kuti vagamuchire dacomitinib (227 varwere) kana gefitinib (225 varwere). Varwere vane metastases yehuropi vaisakodzera.

Pakuteedzana kwepakati pemwedzi makumi maviri neshanu, median PFS yaive 22.1 mwedzi ye dacomitinib vs 14.7 mwedzi yegefitinib; subgroup inoongorora zvakare inofarira dacomitinib. Mhinduro gumi nembiri dzakazara dzakanyorwa mu dacomitinib boka vs 9.2 muboka regefitinib. Izvo zvinangwa zvekupindura mitengo zvaive, zvakadaro, zvakafanana (4% ye dacomitinib uye 75% yegefitinib; P = .72).

Varwere makumi maviri nemumwe vanogamuchira dacomitinib vane chiitiko chakakomba chine chekuita nekurapa (AE); izvi zvaive zvechokwadi nezvevarwere gumi vanogamuchira gefitinib. Kurapa-kwakabatana kurapa kwakaudzwa kwevarwere vaviri vanogashira dacomitinib vs 10 yegefitinib.

Vanyori vakapedzisa kuti "dacomitinib kurapwa kwaive kwakakwirira kupfuura gefitinib zvine chekuita ne [PFS] uye nguva yekupindura mukurapa kwekutanga kwevarwere vane EGFR-mutation-positive NSCLC uye inofanirwa kutarisirwa senzira nyowani yekurapa yevagari. ”

 

Maitiro Ekutenga Dacomitinib Powder pamhepo?

Kune vazhinji vatengesi / vagadziri ve dacomitinib powder mumusika, kutsvaga chaiko kwakakosha kwazvo kuvanhu vese vanoda chigadzirwa ichi nekukurumidza. Kana isu tasarudza kutenga dacomitinib powder mumusika, tinofanirwa kudzidza rumwe ruzivo nezvazvo, kuziva mashandisiro uye mashandiro ekuita, chero njodzi patinotora dacomitinib powder…. Uye zvakare, mutengo uye mhando zvinofanirwa kuve zvatinonetseka tisati tazvitenga.

Mushure mekunge taongorora dhata kubva kumusika, tichienzanisa vatengesi vazhinji, AASraw inotarisa sarudzo dzakanaka kune avo vanhu vanoda kutenga zvakawanda dacomitinib upfu, kugadzirwa kwavo kwaidzorwa zvakanyanya pasi peCGMP mamiriro, hunhu hunogona kuteverwa chero nguva uye ivo vangangopa ese miedzo yekuyedza kana iwe ukairaira. Kana iri iyo dacomitinib yeupfu inodhura / mutengo, inofanira kuve zvine musoro, mumaziso angu. Nekuti ini ndawana mitengo yakawanda kubva kune vakasiyana vatengesi, zvichienzaniswa nehunhu, ndinofunga aasraw ichave isiri yakaipa sarudzo.

 

Reference

[1] Kobayashi Y, Fujino T, Nishino M, et al. EGFR T790M neC797S shanduko senzira dzekuwana kuramba dacomitinib. J Thorac Oncol. 2018; 13 (5): 727-731. doi: 10.1016 / j.jtho.2018.01.009.

[2] Kris MG, Camidge DR, Giaccone G, uye al. Targeting HER2 aberrations sevatyairi vanokonzeresa mukenza yemapapu: chikamu II kutongwa kwepan-HER tyrosine kinase inhibitor dacomitinib mune varwere vane HER2-mutant kana akasimbisa matumbu. Ann Oncol. 2015; 26 (7): 1421-1427. doi: 10.1093 / annonc / mdv383.

[3] Paki K, Tan EH, O'Byrne K, et al. Afatinib maringe gefitinib seyekutanga-kurapwa kurapwa kwevarwere vane EGFR mutation-yakanaka isiri-diki-maseru kenza yemapapu (LUX-Lung 7): chikamu 2B, yakavhurika-chitaridzi, kurongwa kwakarongedzwa kutongwa. Lancet Oncol. 2016; 17 (5): 577-589. doi: 10.1016 / S1470-2045 (16) 30033-X.

[4] Lacouture INI, Keefe DM, Sonis S, et al. Chikamu chechipiri II kudzidza (ARCHER 1042) kuongorora prophylactic kurapwa kwe dacomitinib-inosimudzira dermatologic uye gastrointestinal zviitiko zvakashata mune yepamusoro isiri-diki-sero kenza yemapapu Ann Oncol. 2016; 27 (9): 1712-1718. doi: 10.1093 / annonc / mdw227.

[5] Reckamp KL, Giaccone G, Camidge DR, et al. Chikamu chechipiri kutongwa kwe dacomitinib (PF ‐ 2), pani yemuromo, isingadzoreke- HER (human epidermal grow factor receptor) inhibitor, mune varwere vane epamberi isiri-diki kenza yemapapu yemapapu mushure mekukundikana kwemakemikari epamberi uye erlotinib. Gomarara. 00299804; 2014 (120): 8–1145. doi: 1154 / cncr.10.1002.

[6] Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET kukwidziridzwa kunotungamira kune gefitinib kuramba mumukenza wemapapu nekumikidza chiratidzo cheEERBB3. Sayenzi. 2007; 316 (5827): 1039-1043. doi: 10.1126 / science.1141478.

[7] Liu X, Wang P, Zhang C, et al. Epidermal kukura factor receptor (EGFR): Nyeredzi iri kusimuka munguva yemushonga chaiwo wekenza yemapapu. Oncotarget. 2017; 8 (30): 50209-50220.

[8] Girard N. Kugadzirisa mhedzisiro muEGFR shanduko-yakanaka NSCLC: ndeipi tyrosine kinase inhibitor uye riini? Ramangwana Oncol 2018.

[9] Inoue A, Kobayashi K, Maemondo M, et al. Yekupedzisira mhedzisiro yekupona mhedzisiro yeNEJ002, danho rechitatu kuyedza kuenzanisa gefitinib kune carboplatin (CBDCA) pamwe paclitaxel (TXL) seyekutanga-kurapwa kurapwa kwekenza isiri-diki maseru kenza yemapapu (NSCLC) ine EGFR shanduko. J Clin Oncol 2011; 29: 7519.

[10] Tsvaga LV, Yang JC, Yamamoto N, et al. Chikamu chechitatu III cheafatinib kana cisplatin pamwe pemetrexed mune varwere vane metastatic lung lung adenocarcinoma ine EGFR shanduko. J Clin Oncol 2013; 31: 3327-34.

[11] Lin JJ, Cardarella S, Lydon CA, et al. Kupona Kwemakore mashanu muEGFR-Mutant Metastatic Lung Adenocarcinoma Yakagadziriswa neEGFR-TKIs. J Thorac Oncol 2016; 11: 556-65.

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