ALK-Positive Lung Cancer Drug "Ceritinib (LDK378)" - AASraw
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Wotsogolera

 

    1. Ceritinib Adavomerezedwa Kuti Agwiritse Ntchito ku EU
    2. Kufotokozera kwa Ceritinib
    3. Kodi Ceritinib imagwira ntchito bwanji pochiza NSCLC?
    4. Nanga Bwanji Zogwiritsa Ntchito Zamankhwala a Ceritinib?
    5. Kodi Mungasunge Bwanji Ceritinib (LDK378)?
    6. Zotsatira zoyipa za Ceritinib ndi ziti?
    7. Ndi Ubwino Wina Wotani wa Ceritinib Wawonetsedwa M'maphunziro?
    8. Ceritinib Amalandira Mzere Woyamba Kuvomerezeka kwa FDA kwa Khansa ya M'mapapo ya ALK-Positive

 

Ceritinib Adavomerezedwa Kugwiritsa Ntchito mu EU

Ceritinib (CAS: 1032900-25-6) yawonetsedwa kuti ndi othandiza pochiza odwala omwe matenda awo amapita mkati kapena atangomaliza chithandizo ndi alireza ndipo omwe pakali pano ali ndi njira zochepa zochiritsira, komanso odwala omwe sanalandirepo chithandizo kale. Ponena za chitetezo, zovuta zoyipa za Ceritinib zimawoneka ngati zokhozeka.

European Medicines Agency chifukwa chake idaganiza kuti maubwino a Ceritinib ndi akulu kuposa zoopsa zake ndipo idalimbikitsa kuti ivomerezedwe kuti igwiritsidwe ntchito ku EU.

Ceritinib adapatsidwa 'chilolezo' chifukwa choyambirira panali umboni wambiri wonena za mankhwalawo. Pomwe kampaniyo imapereka zina zowonjezera zofunikira, chilolezo chasinthidwa kuchoka pamikhalidwe mpaka kuvomerezedwa kwathunthu.

Muyenera kukhala ndi chidwi ndi izi, Tiwerenge zambiri zokhudza izi Wotsogolera:

 

Kufotokozera kwa Ceritinib

Ceritinib imagwiritsidwa ntchito pochiza achikulire omwe ali ndi anaplastic lymphoma kinase (ALK) -osangalatsa metastatic khansa ya m'mapapo yosakhala yaying'ono (NSCLC) kutsatira kulephera (chachiwiri kukana kapena kusagwirizana) kwamankhwala am'mbuyomu a crizotinib. Pafupifupi 4% ya odwala omwe ali ndi NSCLC ali ndi chromosomal rearrangement yomwe imapanga jini losakanikirana pakati pa EML4 (echinoderm microtubule-protein-like 4) ndi ALK (anaplastic lymphoma kinase), zomwe zimabweretsa zochitika za kinase zomwe zimathandizira khansa ya khansa ndipo zimawoneka ngati zikuyendetsa phenotype yoyipa.

Ceritinib imagwiritsa ntchito mphamvu yake yoletsa poletsa autophosphorylation ya ALK, phosphorylation yolumikizidwa ndi ALK ya mapuloteni otsika otsika STAT3, komanso kuchuluka kwa maselo a khansa omwe amadalira ALK. Kutsatira chithandizo ndi crizotinib (m'badwo woyamba wa ALK inhibitor), zotupa zambiri zimayamba kusamva mankhwala chifukwa cha kusintha kwa zotsalira zazikulu za "mlonda wa pachipata" wa enzyme. Izi zidapangitsa kuti pakhale njira zatsopano za m'badwo wachiwiri wa ALK zoletsa monga ceritinib kuthana ndi kukana kwa crizotinib. A FDA adavomereza ceritinib mu Epulo 2014 chifukwa chakuyankha modabwitsa (56%) kumatumbo osagonjetsedwa ndi crizotinib ndipo adaisankha ndi mankhwala amasiye.

 

Kodi Ceritinib imagwira ntchito bwanji pochiza NSCLC?

Ceritinib ndi inhibitor yosankha komanso yamphamvu ya anaplastic lymphoma kinase (ALK). Mwachilengedwe, ALK imagwira ntchito ngati gawo lofunikira pakukula ndi magwiridwe antchito amisempha yamanjenje. Komabe, kusunthika kwa chromosomal ndi kusakanikirana kumabweretsa mtundu wa ALK womwe umakhala wokhudzidwa ndi NSCLC. Chifukwa chake Ceritinib imaletsa mavitamini osinthasinthawa ndikuletsa kuchuluka kwa ma cell, pamapeto pake kuyimitsa kupitilira kwa khansa. Chifukwa chakuti ceritinib imawerengedwa kuti ndi chithandizo chamankhwala cha khansa, mayeso ovomerezeka a FDA amafunikira kuti adziwe omwe ali odwala ceritinib. Mayesowa, opangidwa ndi Roche, ndi VENTANA ALK (D5F3) CDx Assay ndipo amagwiritsidwa ntchito kuzindikira odwala ALK omwe ali ndi NSCLC omwe angapindule ndi mankhwala a ceritinib.

AASraw ndiye katswiri wopanga Ceritinib.

Chonde dinani apa kuti mumve zambiri: Ochezera ife

 

Nanga Bwanji Zogwiritsa Ntchito Zamankhwala a Ceritinib?

Ceritinib (LDK378) ndi mankhwala omwe amagwiritsidwa ntchito pochiza khansa ya m'mapapo yopanda tinthu tating'onoting'ono yomwe tafalikira mbali zina za thupi ndipo ili ndi aplastic lymphoma kinase (ALK) yothandiza. Ikuwerengedwanso pochiza mitundu ina ya khansa. Ceritinib imatseka mapuloteni opangidwa ndi mtundu wa ALK. Kuletsa puloteni iyi kumatha kuletsa kukula ndi kufalikira kwa maselo a khansa. Ceritinib ndi mtundu wa tyrosine kinase inhibitor.

 

Wotsogolera

 

Kodi Mungasunge Bwanji Ceritinib (LDK378)?

Sungani Ceritinib (LDK378) mu chidebe chomwe chidabwera, chatsekedwa mwamphamvu, komanso chosafikirika ndi ana. Zisunge kutentha komanso kutali ndi kuwala, kutentha kwambiri ndi chinyezi (osati kubafa).

Mankhwala osafunikira ayenera kutayidwa munjira zapadera zowonetsetsa kuti ziweto, ana, ndi anthu ena sangamwe. Komabe, simuyenera kutsuka Ceritinib (LDK378) mchimbudzi. M'malo mwake, njira yabwino yoperekera mankhwala anu ndikadongosolo lobwezera mankhwala. Lankhulani ndi wamankhwala wanu kapena lemberani dipatimenti yakunyumba / yobwezeretsanso kwanuko kuti muphunzire zamapulogalamu obwezeretsa mdera lanu. Onani fayilo ya Kutaya Kwabwino kwa FDA ya tsamba la Medicines kuti mumve zambiri ngati mulibe pulogalamu yobwezera.

Ndikofunika kuti mankhwala onse asamaoneke komanso kuti ana azikhala ndi zida zambiri (monga mapiritsi apakati pa mlungu ndi madontho, maso, mavitamini, ndi inhalers) sagonjetsedwa ndi ana ndipo akhoza kuwatsegula mosavuta. Pofuna kuteteza ana aang'ono ku poizoni, nthawi zonse mutseka makapu a chitetezo ndipo nthawi yomweyo perekani mankhwalawa pamalo otetezeka - omwe ali pamwamba ndi kutali ndi osawona ndi kufika.

 

Zotsatira zoyipa za Ceritinib ndi ziti? 

Zinthu zofunika kuzikumbukira pazotsatira zoyipa za ceritinib:

▪ Anthu ambiri samakumana ndi zovuta zonse zomwe zalembedwa.

▪ Zotsatira zoyipa zimadziwikiratu malinga ndi momwe zimakhalira komanso kutalika kwake.

▪ Zotsatira zoyipa zimasinthidwa ndipo zimatha pambuyo poti mankhwala akwana.

▪ Pali njira zambiri zothandizira kuchepetsa kapena kupewa zotsatira zoyipa.

▪ Palibe ubale pakati pa kupezeka kapena kuopsa kwa zotsatirapo zake ndi mphamvu ya mankhwala.

 

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

▪ Kutsekula m'mimba

▪ Hemoglobin inachepa

▪ Wonjezerani michere ya chiwindi

▪ Nsautso

▪ Kusanza

▪ Kuchuluka kwa creatinine

▪ Kupweteka m'mimba

▪ Kutopa

▪ Glucose yawonjezeka

▪ Kuchepetsa phosphate

▪ Kuchepetsa njala

AASraw ndiye katswiri wopanga Ceritinib.

Chonde dinani apa kuti mumve zambiri: Ochezera ife

 

Zotsatirazi ndizotsatira zoyipa zochepa (zomwe zimachitika pafupifupi 10-29%) ya odwala omwe alandila ceritinib:

▪ Kudzimbidwa

▪ Lipase wakula

▪ Matenda otupa m'mimba (Kutentha kwa mtima, matenda am'mimba, dysphagia)

▪ Ziphuphu

▪ Bilirubin (yathunthu) yawonjezeka

Zotsatira zoyipa, koma zosazolowereka kwambiri za ceritinib ndi pneumonitis (kutupa kwa mapapo). Izi zikachitika, nthawi zambiri zimaphatikizana ndi kupuma movutikira ndi chifuwa kapena malungo otsika kwambiri omwe amafunikira kuchipatala. Zizindikiro zitha kukhala zofananira ndi zizindikilo zaku khansa yamapapu. Lumikizanani ndi omwe akukuthandizani nthawi yomweyo ngati muli ndi zizindikilo zatsopano kapena zoyipa.

Chotsatira china chachikulu koma chosazolowereka cha ceritinib ndikusintha kwa EKG. Sizovuta zonse zomwe zalembedwa pamwambapa. Zina zomwe ndizosowa (zomwe zimachitika ochepera 10% ya odwala) sizidalembedwe apa. Komabe, nthawi zonse muyenera kudziwitsa omwe akukuthandizani ngati mukukumana ndi zachilendo.

 

Wotsogolera

 

Ndi Ubwino Wina Wotani wa Ceritinib Wawonetsedwa M'maphunziro?

M'maphunziro awiriwa, okhudzana ndi odwala 303, mankhwalawa sanayerekezeredwe ndi chithandizo china chilichonse. Kuyankha kuchipatala kunayesedwa pogwiritsa ntchito sikani yamthupi ndi njira zofananira zomwe zimagwiritsidwa ntchito zotupa zolimba, poyankha kwathunthu ndi pomwe wodwalayo analibe zizindikiro zotsalira za khansa. Pakafukufuku wina 56% ya odwala omwe adapatsidwa ceritinib (92 of 163) adawonedwa ndi madotolo omwe adalandira kuti awonetsa kuyankha kwathunthu kapena pang'ono pamankhwalawo. Nthawi yayitali yankho anali miyezi 8.3. Pakafukufuku wachiwiri, kuchuluka kwa mayankho anali 41% (57 ya odwala 140) ndipo kutalika kwa mayankho anali miyezi 10.6.

Phunziro lachitatu mwa odwala 231, ceritinib idafaniziridwa ndi chemotherapy wamba (mankhwala ochizira khansa). Zotsatira zidawonetsa kuti odwala omwe amapatsidwa ceritinib amakhala pafupifupi miyezi 5.4 popanda matenda awo kukulira (kupitirira pang'onopang'ono) poyerekeza ndi miyezi 1.6 ya odwala omwe apatsidwa chemotherapy yokhazikika.

Ceritinib awonetsedwanso kuti ndi othandiza pochiza odwala omwe anali asanalandirepo kafukufuku wina mwa odwala 376. Odwala omwe amapatsidwa ceritinib amakhala pafupifupi miyezi 16.6 popanda matenda awo kukulira kuyerekeza ndi miyezi 8.1 ya odwala omwe amapatsidwa chemotherapy wamba.

 

Ceritinib Amalandira Mzere Woyamba Kuvomerezeka kwa FDA kwa Khansa ya M'mapapo ya ALK-Positive

A FDA adakulitsa kuvomereza kwa ceritinib. Wothandizirayo tsopano wavomerezedwa ngati chithandizo choyamba cha odwala omwe ali ndi khansa yam'mapapo yam'mapapo, yamtundu wa ALK, yosakhala yaying'ono. US Food and Drug Administration (FDA) yakulitsa kuvomereza kwa ceritinib. Wothandizirayo tsopano wavomerezedwa ngati mankhwala oyamba mwa odwala omwe ali ndi khansa yam'mapapo yam'mapapo (NSCLC).

Ceritinib (LDK378) idavomerezedwa kale ku 2014 kwa ALK-positive metastatic NSCLC mwa odwala omwe anali atapita patsogolo kapena osagwirizana ndi crizotinib. Wothandizirayo ndi ALK inhibitor wosankha, wokhala ndi pothekera makumi awiri koposera crizotinib.

Chizindikiro chatsopanochi chazikidwa pazotsatira za mayeso a ASCEND-4, omwe zotsatira zake zidasindikizidwa mu Januware chaka chino ku Lancet. Mlanduwo udasinthitsa odwala 376 omwe ali ndi metastatic NSCLC yokhala ndi ALK yokonzanso kwa ceritinib (odwala 189) kapena platinamu-pemetrexed doublelet therapy (odwala 187).

Mapeto oyambira anali kupulumuka kopanda kupita patsogolo, ndipo ceritinib inali yothandiza kwambiri. Kupulumuka kwapakatikati kwapakatikati kunali miyezi 16.6 ndi mankhwala owerengera, poyerekeza ndi miyezi 8.1 m'manja mwa chemotherapy, poyerekeza ndi 0.55 (95% CI, 0.42-0.73; P <.0001).

Kuchuluka kwa mayankho kunalinso kwabwino, pa 73% ndi ceritinib ndi 27% ndi chemotherapy. Nthawi yoyankha yapakatikati inali miyezi 23.9 yokhala ndi ceritinib ndi miyezi 11.1 yokhala ndi platinamu / pemetrexed. Pakadali pano, zambiri zopulumuka sizikhala zazing'ono. Ceritinib anapatsidwa mwayi wopezeka ndi Therapy Breakthrough Therapy ndi a FDA, komanso kuwunikiranso koyambirira kwa mankhwala oyamba mwa odwalawa.

Kafukufuku wa ASCEND-4 adawunikiranso kuchuluka kwa mayankho mwa odwala omwe ali ndi zotupa zoyipa zapakati. Zomwe zatsimikiziridwa kuti sizingatheke poyankha zinali 57% ndi ceritinib, poyerekeza ndi 22% ndi chemotherapy.

Zochitika zovuta kwambiri (AEs) zidachitika mu 38% ya odwala omwe adachitidwa ndi ceritinib, ndipo ma AE omwe amatsogolera pakusiya mankhwalawa adachitika mu 12%. Kusokonezeka kwa mlingo chifukwa cha AEs kunawoneka mu 77% ya odwala ceritinib, ndipo 66% amafunika kuchepetsa mlingo. Ma AE ofala kwambiri omwe amamwa mankhwalawa mu ASCEND-4 amaphatikizapo kutsegula m'mimba, nseru, kusanza, kutopa, ndi kupweteka m'mimba. "Kuvomereza kwamasiku ano kukuyimira gawo lotsatira pakukula kwa Zykadia ngati njira yothandizira ALK-metastatic NSCLC, kubweretsa mankhwala ofunikirawa kwa odwala omwe akufunikirabe," watero a CEO a Novartis Oncology, a Bruno Strigini, atolankhani.

AASraw ndiye katswiri wopanga Ceritinib.

Chonde dinani apa kuti mumve zambiri: Ochezera ife

 

Reference

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[2] Soria JC, Tan DS, Chiari R, Wu YL, Paz-Ares L, Wolf J, ndi al. (Marichi 2017). "Mzere woyamba wa ceritinib motsutsana ndi chemotherapy yochokera ku platinamu mu khansa yamapapu yam'mapapo (ALCEND-4) yotsogola yomwe yakonzedweratu ya ALK: kafukufuku wosasinthika, wotseguka, gawo la 3". Lancet. 389 (10072): 917–929.

[3] Xuan C, Gunduz V. "NSCLC MARKET - Kuwonetseratu Kwa Zamankhwala Padziko Lonse & Kusanthula Kwamsika ku 2025". Kukula Kwa Mankhwala Osokoneza bongo & Kutumiza. Ayi Novembala – Disembala 2016.

[4] "FDA ivomereza Ceritinib ya khansa ya khansa ya ALK-Positive Lung". Kutha. Epulo 29, 2014.

[5] Au TH, Cavalieri CC, Stenehjem DD Ceritinib: Choyambirira cha asayansi // Oncology pharmacy practice. - 2017. - Vol. 23 (8). - P. 611 (doi: 10.1177 / 1078155216672315).

[6] Nishio M, Murakami H, Horiike A, Takahashi T, Hirai F, Suenaga N, Tajima T, Tokushige K, Ishii M, Boral A, Robson M, Seto T: Gawo I Phunziro la Ceritinib (LDK378) mwa Odwala aku Japan Opita Patsogolo, Anaplastic Lymphoma Kinase-Yokonzedwanso Khansa Yapang'ono Yam'mapapo kapena Zotupa Zina. J Thorac Oncol. 2015 Jul; 10 (7): 1058-66. onetsani: 10.1097 / JTO.0000000000000566. [Adasankhidwa: 26020125].

[7] Galkin AV, Melnick JS, Kim S, Hood TL, Li N, Li L, Xia G, Steensma R, Chopiuk G, Jiang J, Wan Y, Ding P, Liu Y, Sun F, Schultz PG, Grey NS, Warmuth M : Kuzindikiritsa NVP-TAE684, choletsa champhamvu, chosankha, komanso chothandiza cha NPM-ALK. Proc Natl Acad Sci US A. 2007 Jan 2; 104 (1): 270-5. Epub 2006 Dec 21. [Adasankhidwa: 17185414].

[8] Marsilje TH, Pei W, Chen B, Lu W, Uno T, Jin Y, Jiang T, Kim S, Li N, Warmuth M, Sarkisova Y, Sun F, Steffy A, Pferdekamper AC, Li AG, Joseph SB, Kim Y , Liu B, Tuntland T, Cui X, Grey NS, Steensma R, Wan Y, Jiang J, Chopiuk G, Li J, Gordon WP, Richmond W, Johnson K, Chang J, Groessl T, Iye YQ, Phimister A, Aycinena A, Lee CC, Bursulaya B, Karanewsky DS, Seidel HM, Harris JL, Michellys PY: Kuphatikizika, ubale wazomwe zikuchitika, komanso mu vivo mphamvu ya buku lamphamvu kwambiri komanso losankha la aplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2- (2-isopropoxy-5-methyl-4- (piperidin-4-yl) phenyl) -N4- (2- (isopropylsulf onyl) phenyl) pyrimidine-2,4-diamine (LDK378) pakadali pano mu gawo 1 ndi 2 mayesero. J Med Chem. 2013 Jul 25; 56 (14): 5675-90. onetsani: 10.1021 / jm400402q. Epub 2013 Jun 26. [Adasankhidwa: 23742252].

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