Kuwunika kwa Dacomitinib Dacomitinib: Kodi Mungamuthandize Bwanji NSCLC? - AASraw
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Chidwi

 

  1. FDA ivomereza dacomitinib ya khansa yam'mapapo yam'mapapo osakhala yaying'ono
  2. Kodi Khansa Yam'mapapo Yomwe Sili Ying'ono Ndi Chiyani?
  3. Kugwiritsa ntchito kuchipatala kwa Dacomitinib mu khansa ya m'mapapo yosakhala yaying'ono
  4. Ndemanga ya Dacomitinib
  5. Njira ya Dacomitinib yogwirira ntchito
  6. Ntchito za Dacomitinib
  7. Zotsatira za Dacomitinib
  8. Chithandizo cha Khansa ya M'mapapo Yaying'ono: Dacomitinib VS Gefitinib
  9. Kodi Mungagule Bwanji Dacomitinib Powder pa intaneti?

 

FDA ivomereza dacomitinib ya khansa yam'mapapo yam'mapapo osakhala yaying'ono

Pa Seputembara 27, 2018, Food and Drug Administration idavomereza mapiritsi a dacomitinib (VIZIMPRO, Pfizer Pharmaceutical Company) yothandizira odwala oyamba omwe ali ndi metastatic khansa ya m'mapapo yosakhala yaying'ono (NSCLC) yokhala ndi epidermal grow factor receptor (EGFR) exon 19 kufufutidwa kapena exon 21 L858R m'malo osintha monga momwe zimadziwika ndi mayeso ovomerezeka a FDA.

Kuvomerezeka kutengera kuyesedwa kosasinthika, kosiyanasiyana, koyeserera, kuyeserera kogwira ntchito (ARCHER 1050; NCT01774721) kuyerekeza chitetezo ndi mphamvu ya dacomitinib ndi gefitinib mwa odwala 452 omwe ali ndi NSCLC yosasunthika. Odwala amafunikira kuti asalandire chithandizo chamatenda am'mimba kapena matenda obwerezabwereza osachepera miyezi 12 yopanda matenda akamaliza njira ya non-EGFR TKI; ntchito yaku Eastern Cooperative Oncology Group ya 0 kapena 1; ndi EGFR exon 19 kuchotsa kapena exon 21 L858R m'malo osintha. Odwala adasinthidwa mwachisawawa (1: 1) kuti alandire dacomitinib 45 mg pakamwa kamodzi tsiku lililonse kapena gefitinib 250 mg pakamwa kamodzi tsiku lililonse mpaka kukula kwa matenda kapena poizoni wosavomerezeka.

Mlanduwu udawonetsa kusintha kwakukuru pakupulumuka kopanda kupita patsogolo; palibe kusintha pamayankho onse kapena kupulumuka konse komwe kudawonetsedwa. Kupulumuka kwapakatikati kwapakatikati, kutsimikiziridwa ndi komiti yodziyimira payokha. anali miyezi 14.7 ndi 9.2 m'manja mwa dacomitinib ndi gefitinib, motsatana (chiopsezo cha 0.59; 95% CI: 0.47, 0.74; p <0.0001).

Malangizowa amakhala ndi machenjezo ndi zodzitetezera ku matenda am'mapapo am'mapapo (ILD), kutsegula m'mimba, komanso kusintha kwa dermatologic. Mwa odwala 394 omwe adalandira dacomitinib, zovuta zoyipa zidachitika mu 27%. Zovuta zomwe zimachitika chifukwa chosiya dacomitinib anali kutsegula m'mimba ndi ILD. Zotsatira zoyipa kwambiri (> 20%) za dacomitinib zinali zotsekula m'mimba, zotupa, paronychia, stomatitis, kuchepa kwa njala, khungu lowuma, kuchepa thupi, alopecia, chifuwa, ndi pruritus).

 

Kodi Khansa Yam'mapapo Yomwe Sili Ying'ono Ndi Chiyani?

Khansa ya m'mapapo ndi khansa yofala kwambiri padziko lonse lapansi, yomwe imapezeka ndi anthu opitilira 2018 miliyoni padziko lonse lapansi mu 85. Pafupifupi 75 peresenti ya khansa yonse yam'mapapo imadziwika kuti si khungu laling'ono, ndipo pafupifupi XNUMX% ya izi ndi metastatic, kapena kupita patsogolo, pakuzindikira .

EGFR ndi mapuloteni omwe amathandiza maselo kukula ndikugawana. Gulu la EGFR likasinthidwa limatha kupangitsa kuti puloteniyo igwire ntchito mopitilira muyeso ndikupangitsa kuti maselo a khansa apange. Kusintha kwa EGFR kumatha kupezeka mu 10 mpaka 35% ya zotupa za NSCLC padziko lonse lapansi, ndipo kusintha komwe kumachitika kwambiri ndikuchotsa exon 19 ndikutulutsa 21 L858R m'malo mwake, zomwe zimaphatikiza 80% yodziwika yosintha kusintha kwa EGFR. Matendawa amagwirizanitsidwa ndi kuchepa kwa kupulumuka ndipo kupitilira kwa matenda kumakhalabe kovuta.

AASraw ndiye katswiri wopanga Dacomitinib.

Chonde dinani apa kuti mumve zambiri: Ochezera ife

 

Kugwiritsa ntchito kuchipatala kwa Dacomitinib mu khansa ya m'mapapo yosakhala yaying'ono

Dacomitinib ndi m'badwo wachiwiri wa EGFR tyrosine kinase inhibitor (TKI) womwe umamangirira mosalekeza ndikuletsa EGFR / Her1, Her2 ndi Her4 subtypes mofanana ndi ma TKIs ena. Muyeso la ARCHER 1050, kupulumuka kopanda kupita patsogolo kunasintha ndi dacomitinib poyerekeza ndi gefitinib, yothandizira dacomitinib ngati njira yoyamba yothandizira khansa yaying'ono yamapapo yam'mapapo osasintha ndi kusintha kwa EGFR. Ponena za kuchuluka kwa zochitika zoyipa kwambiri, kuchepetsedwa kwa mlingo sikunachepetse mphamvu ya dacomitinib ndipo kumatha kuchepetsa kuchepa komanso kuwopsa kwa zochitika zoyipa. Poganizira momwe kusintha kwa khansa ya m'mapapo ya EGFR-mutant-cell yaying'ono, mutu wamtsogolo kuyerekezera pakati pa dacomitinib ndi osimertinib itha kupereka chidziwitso chofunikira kuti mudziwe nthawi yabwino yothandizira TKI.

 

Chidwi

 

Kuchuluka kwa khansa ya m'mapapo osakhala yaying'ono kwatikakamiza kuti tiganizire za njira zamankhwala, momwe tingapezere njira zabwino? Chidwi chithandizo chidzalimbikitsidwa kwa aliyense. Chotsatira, tiyeni tiwone Chidwi:

 

Ndemanga ya Dacomitinib

Dacomitinib, yopangidwa ngati (2E) -N-16-4- (piperidin-1-yl) koma-2-enamide, ndi gawo losankhidwa kwambiri la quinazalone m'chigawo chachiwiri cha tyrosine kinase inhibitors chomwe chimadziwika ndikumangika kosasinthika madera a ATP a madera a epidermal kukula factor receptor banja kinase. Dacomitinib ndi mankhwala ochizira non-cell-cell lung carcinoma (NSCLC). Ndi choletsa chosankha ndi chosasinthika cha EGFR.

Dacomitinib idapangidwa ndi Pfizer Inc ndikuvomerezedwa ndi a FDA pa Seputembara 27, 2018. Umboni wina m'mabukuwa ukuwonetsa kuthekera kwa kuchiritsa kwa dacomitinib mu mtundu wa khansa yamchiberekero ya epithelial, ngakhale kuli kofunikira kuti kufufuzanso kwina.

Pakadali pano, Dacomitinib ufa (CAS:1110813-31-4) atha kuperekedwa ndi AASraw ochokera ku China.

 

Njira ya Dacomitinib yogwirira ntchito

Dacomitinib ndi chosasinthika chaching'ono cha molekyulu choletsa zochitika za banja la epidermal grow factor receptor (EGFR) (EGFR / HER1, HER2, ndi HER4) tyrosine kinases. Imakwaniritsa choletsa chosasinthika kudzera kolumikizana kophatikizana ndi zotsalira za cysteine ​​m'magawo othandizira a HER receptors. Chiyanjano cha dacomitinib chawonetsedwa kuti chili ndi IC50 ya 6 nmol / L.

Banja la ErbB kapena epidermal grow factor (EGF) limathandizira pakukula kwa chotupa, metastasis, komanso kukana chithandizo chamankhwala poyambitsa njira zosunthira kutsika monga Ras-Raf-MAPK, PLCgamma-PKC-NFkB ndi PI3K / AKT kudzera pa tyrosine phaseji ya kinase yomwe imayendetsedwa ndi carboxy-terminus.1 Pafupifupi 40% yamilandu ikuwonetsa kukulitsa kwa jini la EGFR ndipo 50% ya milanduyo ikuwonetsa kusintha kwa EGFRvIII komwe kumayimira kufufutidwa komwe kumapangitsa kuyambitsa kwa tyrosine kinase domain ya receptor.

 

Ntchito za Dacomitinib

Dacomitinib imavomerezedwa kuchiza: Khansa ya m'mapapo yosakhala yaying'ono (NSCLC) yomwe yasintha (kufalikira mbali zina za thupi). Amagwiritsidwa ntchito ngati chithandizo choyamba kwa odwala omwe zotupa zawo zimakhala ndi kusintha kwa majini a EGFR.

Dacomitinib akuwerengedwanso pochiza mitundu ina ya khansa.

 

Zotsatira za Dacomitinib

Zinthu zofunika kuzikumbukira pazotsatira zoyipa za dacomitinib:

▪ Anthu ambiri sangapeze zovuta zonse za dacomitinib zomwe zalembedwa apa.

▪ Zotsatira zoyipa za Dacomitinib nthawi zambiri zimadziwikiratu malinga ndi momwe zimayambira, kutalika kwake komanso kuuma kwake.

▪ Zotsatira zoyipa za Dacomitinib zidzayamba bwino mankhwala akamaliza.

▪ Zotsatira zoyipa za Dacomitinib zitha kukhala zotheka. Pali njira zambiri zochepetsera kapena kupewa zovuta za dacomitinib.

AASraw ndiye katswiri wopanga Dacomitinib.

Chonde dinani apa kuti mumve zambiri: Ochezera ife

 

Zotsatira zotsatirazi ndizofala (zomwe zimachitika kuposa 30%) kwa odwala omwe amatenga dacomitinib:

▪ Ziphuphu pakhungu

▪ Matenda a msomali abacteria kapena fungal (paronychia)

▪ Khungu louma

▪ Ochepera albumin

▪ Kashiamu wochepa

▪ Kuchuluka kwa shuga m'magazi

▪ Kutsekula m'mimba

▪ Zilonda za pakamwa

▪ Kuchepetsa njala

▪ Kuchepa kwa magazi m'thupi (hemoglobin yotsika)

▪ Kuchuluka kwa maselo oyera a magazi

▪ Kuchulukitsa michere ya chiwindi

 

Izi ndizotsatira zoyipa zochepa (zomwe zimachitika mu 10-29%) kwa odwala omwe alandila dacomitinib:

▪ Kupweteka pachifuwa

▪ Kusagona

▪ Tsitsi

▪ Kuyabwa

▪ Kufiira, kutupa, ndi kupweteka m'manja mwake kapena / kapena kupondera kwa mapazi

▪ Potaziyamu wambiri, magnesium ndi sodium

▪ Kuchepetsa thupi

▪ Nausea

▪ Kudzimbidwa

▪ Kupweteka kwa ziwalo

▪ Kumva kupweteka kwa mafupa ndi mafupa

▪ Kufooka / kusowa mphamvu

▪ Kutupa kapena matenda m'maso

▪ Kuchuluka kwa seramu creatinine

▪ Chifuwa, zizindikiro za m'mphuno, kuvutika kupuma komanso matenda am'mapapo

Sizovuta zonse zomwe zalembedwa pamwambapa. Zotsatira zoyipa zomwe zimapezeka kawirikawiri - zomwe zimachitika ochepera 10 peresenti ya odwala - sizinalembedwe pano. Koma nthawi zonse muyenera kudziwitsa omwe akukuthandizani ngati mukukumana ndi zachilendo.

 

Chithandizo cha Khansa ya M'mapapo Yaying'ono: Dacomitinib VS Gefitinib

Mwa odwala omwe ali ndi vuto la EGFR-positive, non-brain metastatic non-small cell lung cancer (NSCLC), mzere woyamba wa dacomitinib umapangitsa kupulumuka kopitilira patsogolo (PFS) pa gefitinib, malinga ndi kafukufuku wapa phase 3 wofalitsidwa mu The Lancet Oncology.Chidwi

Mbadwo woyamba EGFR-tyrosine kinase inhibitors (TKIs), kuphatikiza gefitinib, amagwiritsidwa ntchito pamzere woyamba kwa odwala omwe ali ndi matenda a EGFR, omwe amakhala pakati pa 10% ndi 44% yamapapo adenocarcinomas onse. Kafukufuku wam'mbuyomu sanazindikire ngati m'badwo wachiwiri EGFR-TKIs ndi wapamwamba kuposa mitundu yoyamba.

Pamalemba otsegukawa, osasinthika (ARCHER 1050; Chidziwitso cha ClinicalTrials.gov: NCT01774721), yomwe olemba adalemba ndi gawo loyamba la 3 kufananizira m'badwo wachiwiri EGFR-TKI ndi m'badwo woyamba EGFR-TKI munthawi imeneyi. , ofufuza adalembetsa odwala 452 kuti alandire dacomitinib (odwala 227) kapena gefitinib (odwala 225). Odwala omwe ali ndi metastases yamaubongo sanali oyenerera.

Pakutsatira kwapakatikati kwa miyezi 22.1, PFS yapakatikati inali miyezi 14.7 ya dacomitinib vs 9.2 miyezi ya gefitinib; Kafukufuku wamagulu ang'onoang'ono adakondanso dacomitinib. Mayankho khumi ndi awiri athunthu adalembedwa mgulu la dacomitinib vs 4 pagulu la gefitinib. Mulingo woyankhira poyankha unali wofanana (75% ya dacomitinib ndi 72% ya gefitinib; P = .4234).

Odwala makumi awiri mphambu awiri omwe amalandira dacomitinib adakumana ndi vuto lalikulu lokhudzana ndi chithandizo (AE); Izi zinali choncho ndi odwala 10 omwe amalandira gefitinib. Imfa zokhudzana ndi chithandizo zidanenedwa kwa odwala 2 omwe amalandira dacomitinib vs 1 ya gefitinib.

Olembawo anamaliza kuti "chithandizo cha dacomitinib chinali choposa alireza mokhudzana ndi [PFS] komanso nthawi yayitali poyankha chithandizo cha mzere woyamba wa odwala omwe ali ndi EGFR-mutation-NSCLC ndipo ayenera kuwonedwa ngati njira yatsopano yothandizira anthuwa. ”

 

Kodi Mungagule Bwanji Dacomitinib Powder pa intaneti?

Pali ogulitsa / opanga ambiri a dacomitinib ufa pamsika, kupeza wowona ndikofunikira kwambiri kwa anthu onse omwe amafunikira izi mwachangu. Tikaganiza zogula ufa wa dacomitinib pamsika, tifunika kuphunzira zambiri za izi, kudziwa momwe tingagwiritsire ntchito ndi momwe amagwirira ntchito, zoopsa zilizonse tikatenga dacomitinib powder…. Kuphatikiza apo, mtengo ndi mtundu wake ziyenera kukhala nkhawa zathu tisanagule.

Titasanthula madata ochokera kumsika, poyerekeza ambiri ogulitsa, AASraw imawoneka ngati njira yabwino kwa anthu omwe akufuna kugula zambiri dacomitinib ufa, kupanga kwawo kumayang'aniridwa mosamalitsa pansi pa cGMP, mtunduwo ukhoza kutsatiridwa nthawi iliyonse ndipo atha kupereka malipoti onse oyesa mukamaitanitsa. Ponena za mtengo wa dacomitinib powder / mtengo, ziyenera kukhala zomveka, m'maso mwanga. Chifukwa ndili ndi mitengo yambiri kuchokera kwa ogulitsa osiyanasiyana, poyerekeza ndi mtundu, ndikuganiza kuti aasraw sikhala chisankho choyipa.

 

Reference

[1] Kobayashi Y, Fujino T, Nishino M, et al. Kusintha kwa EGFR T790M ndi C797S ngati njira zotsutsana ndi dacomitinib. J Thorac Oncol. 2018; 13 (5): 727-731. onetsani: 10.1016 / j.jtho.2018.01.009.

[2] Kris MG, Camidge DR, Giaccone G, ndi al. Kulimbana ndi kusokonekera kwa HER2 ngati oyendetsa khansa yam'mapapo: gawo lachiwiri kuyesedwa kwa pan-HER tyrosine kinase inhibitor dacomitinib mwa odwala HER2-mutant kapena amplified tumors. Ann Oncol. 2015; 26 (7): 1421–1427. onetsani: 10.1093 / annonc / mdv383.

[3] Paki K, Tan EH, O'Byrne K, et al. Afatinib motsutsana ndi gefitinib ngati chithandizo choyamba cha odwala omwe ali ndi khansa ya m'mapapo yam'mapapo (LUX-Lung 7): Lancet Oncol. 2; 2016 (17): 5-577. onetsani: 589 / S10.1016-1470 (2045) 16-X.

[4] Kuchotsa INE, Keefe DM, Sonis S, et al. Kafukufuku wachiwiri (ARCHER 1042) kuwunika mankhwala opatsirana a dacomitinib-omwe amachititsa dermatologic ndi m'mimba zochitika zovuta mu khansa yaying'ono yamapapo yam'mapapo. Ann Oncol. 2016; 27 (9): 1712-1718. onetsani: 10.1093 / annonc / mdw227.

[5] Reckamp KL, Giaccone G, Camidge DR, ndi al. Gawo lachiwiri la mayesero a dacomitinib (PF ‐ 2), poto wamlomo, wosasunthika-HER (human epidermal growth factor receptor) inhibitor, mwa odwala omwe ali ndi khansa yaying'ono yaying'ono yamapapo atalephera kugwiritsa ntchito chemotherapy ndi erlotinib. Khansa. 00299804; 2014 (120): 8–1145. onetsani: 1154 / cncr.10.1002.

[6] Engelman JA, Zejnullahu K, Mitsudomi T, ndi al. Kukulitsa kwa MET kumabweretsa gefitinib kukana khansa yamapapu poyambitsa kuwonetsa kwa ERBB3. Sayansi. 2007; 316 (5827): 1039-1043. onetsani: 10.1126 / science.1141478.

[7] [Nkhani yaulere ya PMC] [Adasankhidwa] Liu X, Wang P, Zhang C, et al. Epidermal growth factor receptor (EGFR): Nyenyezi yomwe ikukwera munthawi yachipatala cha khansa yamapapo. Chotsani. 2017; 8 (30): 50209-50220.

[8] Girard N. Kupititsa patsogolo zotsatira mu EGFR mutation-positive NSCLC: ndi tyrosine kinase inhibitor liti ndipo liti? Tsogolo la Oncol 2018.

[9] Inoue A, Kobayashi K, Maemondo M, et al. Zotsatira zomaliza zopulumuka za NEJ002, gawo lachitatu lofanizira gefitinib ndi carboplatin (CBDCA) kuphatikiza paclitaxel (TXL) ngati njira yoyamba yothandizira khansa yaying'ono yamapapo yam'mapapo (NSCLC) ndi kusintha kwa EGFR. J Clin Oncol 2011; 29: 7519 (Adasankhidwa)

[10] Lembani LV, Yang JC, Yamamoto N, et al. Gawo lachitatu la afatinib kapena cisplatin kuphatikiza pemetrexed mwa odwala metastatic lung adenocarcinoma ndi kusintha kwa EGFR. J Clin Oncol 2013; 31: 3327-34 (Adasankhidwa)

[11] Lin JJ, Cardarella S, Lydon CA, ndi al. Kupulumuka Zaka Zisanu mu EGFR-Mutant Metastatic Lung Adenocarcinoma Yothandizidwa ndi EGFR-TKIs. J Thorac Oncol. 2016; 11: 556-65. (Adasankhidwa)

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