ALK-Positive Lung Kanesa Fualaʻau "Ceritinib (LDK378)" - AASraw
AASraw gaosia Cannabidiol (CBD) paʻu ma Hemp Taua Suauʻu tele!

Ceritinib

 

    1. Ceritinib Na Faʻamaonia Mo Faʻaaogaina i EU
    2. Ceritinib Faʻamatalaga
    3. Faʻafefea ona galue le Ceritinib mo le togafitia o le NSCLC?
    4. Faʻafefea Faʻaaogaina Ceritinib Medical?
    5. Faʻafefea Ona Teuina Ceritinib (LDK378)?
    6. O a Itu Itu Aafiaga O Ceritinib?
    7. O a isi penefiti o le Ceritinib ua faʻaalia i suʻesuʻega?
    8. Ceritinib Maua le First-Line FDA Faʻamaonia mo ALK-Positive Lung Cancer

 

Ceritinib Na Faʻamaonia mo le Faʻaaogaina i EU

Ceritinib (CAS: 1032900-25-6) na faʻaalia e aoga i le togafitia o tagata mamaʻi o latou faʻamaʻi alualu i luma i le taimi po o le maeʻa togafitiga ma crizotinib ma i latou o loʻo i ai nei faʻatapulaʻaina togafitiga togafitiga, faʻapea foʻi ma tagata mamaʻi e leʻi togafitia muamua. E tusa ai ma le saogalemu, o le leaga aafiaga ma Ceritinib masani foliga vaaia mafai.

O le mea lea na filifili ai le Ofisa o Vailaau a Europa o penefiti a Ceritinib e sili atu nai lo ona tulaga lamatia ma fautuaina e faamaonia mo le faaaogaina i le EU.

Ceritinib na muamua maua 'aiaiga faʻamaonia' aua e tele isi faʻamaoniga e aumai e uiga i le vailaʻau. A o le kamupani na sapalaiina faʻaopopo faʻamatalaga talafeagai, o le faʻatagaga ua suia mai tuʻuina atu i le faʻamaonia atoa.

Oe tatau ona fiailoa e uiga i lenei oloa, Seʻi tatou faitau atili infromation e uiga i Ceritinib:

 

Ceritinib Faʻamatalaga

O loʻo faʻaaogaina Ceritinib mo le togafitiga o tagata matutua ma anaplastic lymphoma kinase (ALK) -positive metastatic Kanesa kanesa laiti e leʻo laʻititi (NSCLC) mulimuli i le le manuia (tulaga lua i le teteʻe poʻo le le faʻapalepale) o muamua crizotinib togafitiga. E tusa ma le 4% o tagata mamaʻi ma le NSCLC o loʻo i ai le toefaʻatulagaina o le chromosomal e faʻatupuina ai le fusion gen i le va o le EML4 (echinoderm microtubule-related protein-pei o le 4) ma le ALK (anaplastic lymphoma kinase), ma e iʻu ai i le faʻatulafonoina gaioiga gaioiga e fesoasoani i le carcinogenesis ma e foliga mai o le taʻavale le phenotype leaga.

O le Ceritinib o loʻo faʻatinoina lona togafitiga e ala i le taofiina o le autophosphorylation o le ALK, o le ALK-mediated phosphorylation o le vaega i lalo o le polotini o le STAT3, ma le faʻateleina o sela o le kanesa o le ALK I le maeʻa ai o togafitiga ma le crizotinib (o le ALK inhibitor o le augatupulaga muamua), o le tele o siama e faʻatupuina le teteʻe i fualaʻau ona o suiga i vaega taua o le "gatekeeper" o le enzyme. O lenei mea na tupu na mafua ai le atinaʻeina o le talaʻaga lona lua ALK taofi e pei o le ceritinib e foʻia ai le tetee a crizotinib. Na faʻamaonia e le FDA le ceritinib ia Aperila 2014 talu ai le maofa tele o le tali atu (56%) agaʻi i tuma e puipuia ai le crizotinib ma ua atofaina i le tulaga o fualaʻau matuaoti.

 

Faʻafefea ona galue le Ceritinib mo le togafitia o le NSCLC?

Ceritinib o se filifilia ma malosi taofiofia o le anaplastic lymphoma kinase (ALK). I masani masani physiology, ALK galuega o se ki laʻasaga i le atinaʻeina ma le faʻagaioiga o neula e faʻaaoga. Ae ui i lea, o le chromosomal translocation ma fusion e faʻatupuina ai se ituaiga oncogenic o le ALK lea na aafia i le alualu i luma o le NSCLC. O le Ceritinib o loʻo galue e taofi le mea lea ua suia, ma taofia ai le faʻateleina o sela, ma ua taofia ai le alualu i luma o le kanesa. Lenei suʻega, atiae e Roche, o le VENTANA ALK (D5F3) CDx Assay ma e faʻaaogaina e faʻailoa ai ALK-lelei NSCLC tagata mamaʻi o le a faʻamanuiaina mai ceritinib togafitiga.

AASraw o le tagata tomai faapitoa gaosia o Ceritinib.

Faʻamolemole kiliki ii mo upusii faʻamatalaga: Faʻafesoʻotaʻi matou

 

Faʻafefea Faʻaaogaina Ceritinib Medical?

Ceritinib (LDK378) o se vailaʻau faʻaogaina e togafitia ai le le-laʻititi sela kanesa kanesa ua salalau atu i isi vaega o le tino ma e anaplastic lymphoma kinase (ALK) lelei. O loʻo suʻesuʻeina foʻi ile togafitia o isi ituaiga kanesa. E poloka e Ceritinib le polotini na faia e le ALK gene. O le poloka o lenei polotini e ono taofia ai le tuputupu aʻe ma le sosolo o sela kanesa. Ceritinib o se ituaiga o tyrosine kinase taofiofia.

 

Ceritinib

 

Faʻafefea Ona Teuina Ceritinib (LDK378)?

Taofi Ceritinib (LDK378) i totonu o le koneteina na sau ai i totonu, tapunia mau, ma mai le aapa atu o tamaiti. Teu i le vevela vevela ma alu ese mai le malamalama, sili atu vevela ma susu (le i totonu o le faletaele).

O vailaʻau e le manaʻomia e tatau ona tiaʻi i ni auala faʻapitoa e mautinoa ai e le mafai ona faʻaumatia e fagafao, tamaiti, ma isi tagata. Peitaʻi, e le tatau ona e lafoa Ceritinib (LDK378) i lalo o le faleuila. Nai lo lena, o le auala sili e lafoa ai au vailaʻau o le ala i se vailaʻau toe foʻi polokalame. Talanoa i lau fomaʻi vailaʻau pe faʻafesoʻotaʻi lau matagaluega o lapisi / toefaʻaoga e te aʻoaʻo ai e uiga i le toe ave i tua o polokalame i lou nuʻu. Vaai i le Lafoaʻiga saogalemu a le FDA o Medicines 'upega tafaʻilagi mo nisi faʻamatalaga pe a fai e te le mauaina se avanoa i se polokalama toe faʻafoʻi.

E taua le taofi uma o vailaau mai le vaai ma aapa atu i tamaiti le tele o koneteina (e pei o mafaufauga i vaiaso taʻitasi ma i latou e tilotilo mata, kulimi, patches, ma inhalers) e le o tamaiti e puipuia ma e mafai e tamaiti laiti ona tatala faigofie. Mo le puipuia o tamaiti laiti mai le 'ona oona, ia tapuni pea le pulou saogalemu ma vave tuu le vailaau i se nofoaga saogalemu - o se tasi o loʻo agai i luga ma mamao ese mai o latou mata ma aapa atu.

 

O a Itu Itu Aafiaga O Ceritinib? 

Mea taua e manatua e uiga i le itu aʻafiaga o le ceritinib:

▪ Tele o tagata e le maua uma aafiaga leaga na lisiina.

▪ O aʻafiaga e masani ona vaʻaia i tulaga o lo latou amataga ma le umi.

▪ O aʻafiaga e toeititi lava suia i taimi uma ma o le a mou atu pe a maeʻa togafitiga.

▪ E tele filifiliga e fesoasoani ai ile faʻaititia poʻo le puipuia o aʻafiaga.

▪ E leai se sootaga i le va o le iai o poʻo le ogaoga o aʻafiaga ma le aoga o vailaʻau.

 

O mea nei o aʻafiaga e masani (tupu i sili atu nai lo le 30%) mo tagata mamaʻi ave ceritinib:

▪ Manava

▪ Ua faaitiitia le hemoglobin

▪ Faateleina i le ate o enzymes

▪ Faanoi

▪ Talosaga

▪ Faʻateleina le foafoa

▪ Paʻu o le manava

▪ Le lavava

▪ Glucose faʻateleina

▪ Faʻapaʻu i le phosphate

▪ Faʻaitiitia le fiaai

AASraw o le tagata tomai faapitoa gaosia o Ceritinib.

Faʻamolemole kiliki ii mo upusii faʻamatalaga: Faʻafesoʻotaʻi matou

 

O nei aʻafiaga e le masani masani aʻafiaga (tupu i tusa o le 10-29%) o tagata mamaʻi mauaina ceritinib:

▪ Papala

▪ Lipase ua faateleina

▪ Faamai o le Esophageal (Mu le fatu, dyspepsia, dysphagia)

▪ Faanatinati

▪ Bilirubin (aofaʻi) faʻateleina

O se ogaoga, ae o ni mea e le masani ai tele o le ceritinib o le pneumonitis (fulafula o le mama). Ina ua tupu lenei itu aafiaga, sa masani ona o faatasi ma manava faigata ma tale po o se maualalo togi fiva manaʻomia falemai. Faʻailoga e ono tutusa ma na faʻailoga mai le kanesa o le mama. Faʻafesoʻotaʻi vave lau fomaʻi tausi soifua pe a iai sau faʻailoga fou pe leaga foi.

Le isi ogaoga ae matua le masani ai aʻafiaga o ceritinib o suiga EKG. E le o aʻafiaga uma e lisi atu i luga. Nisi e seasea (tupu i lalo ifo o le 10% o tagata mamaʻi) e le o lisiina iinei. Peitaʻi, e tatau ona e faʻailoa i taimi uma lau auaunaga faʻasoifua maloloina pe a fai e te maua se faʻailoga e le masani ai.

 

Ceritinib

 

O a isi penefiti o le Ceritinib ua faʻaalia i suʻesuʻega?

I le lua o nei suʻesuʻega, aofia ai ma tagata gasegase e 303, e leʻi faʻatusatusa le vailaʻau ma isi togafitiga. O le tali atu i togafitiga na suʻesuʻeina e ala i le suʻesuʻeina o le tino ma tulaga masani na faaaoga mo tuma maai, faatasi ai ma le tali atoa a o le tagata onosaʻi e leai se toega o faailoga o le kanesa. I se tasi suʻesuʻega 56% o tagata mamaʻi na tuʻuina i le ceritinib (92 o le 163) na iloiloina e fomaʻi faʻafomaʻi na faʻaalia se atoa pe tali atu faʻafuaseʻi i vailaʻau. Ole averesi ole umi ole tali ole 8.3 masina. I le suʻesuʻega lona lua, o le aotelega o tali na faia e 41% (57 o 140 tagata mamaʻi) ma o le averesi o le umi o le tali atu e 10.6 masina.

I le suʻesuʻega lona tolu i 231 tagata mamaʻi, na faʻatusatusa le ceritinib ma le chemotherapy masani (vailaʻau e togafitia ai le kanesa). O iʻuga na faʻaalia ai o tagata mamaʻi na tuʻuina i le ceritinib na nonofo mo le averesi o le 5.4 masina e aunoa ma lo latou faʻamaʻi ua sili atu le leaga (alualu i luma-leai se ola) faʻatusatusa i le 1.6 masina i tagata mamaʻi na maua masani chemotherapy.

Ceritinib ua faʻaalia foi le aoga i le togafitia o tagata mamaʻi e leʻi togafitia muamua i se suʻesuʻega i le 376 o tagata mamaʻi. O tagata mamaʻi na tuʻuina i le ceritinib na nonofo mo le 16.6 masina e aunoa ma lo latou faʻamaʻi na sili atu le leaga faʻatusatusa i le 8.1 masina i tagata mamaʻi na maua i ai le chemotherapy masani.

 

Ceritinib Maua le First-Line FDA Faʻamaonia mo ALK-Positive Lung Cancer

Ua faʻalauteleina e le FDA le faʻamaonia mo le ceritinib. O le sooupu ua faʻamaonia nei o se muamua-laina togafitiga i tagata mamaʻi ma metastatic, ALK-lelei, leai-laʻititi sela sela kanesa. O le US Food and Drug Administration (FDA) ua faʻalauteleina le faʻamaonia mo ceritinib. O le sooupu ua faʻamaonia nei o se muamua-laina togafitiga i tagata mamaʻi ma metastatic, ALK-lelei, leai-laiti-sela sela kanesa (NSCLC).

Ceritinib (LDK378) na faʻamaonia muamua i le 2014 mo le ALK-positive metastatic NSCLC i tagata mamaʻi na alualu i luma pe na le taliaina le crizotinib. O le sooupu o se filifilia tautala tautala ALK, ma le malosi luasefulu taimi o le crizotinib.

O le faʻailoga fou e faʻavae i luga o iʻuga o le ASCEND-4 faamasinoga, o ana faʻaiʻuga na lolomiina ia Ianuari o le tausaga nei i Lancet. O le faamasinoga faʻasolosolo 376 tagata mamaʻi ma metastatic NSCLC ma ALK toe faʻatulagaina i le ceritinib (189 tagata mamaʻi) poʻo le platinum-pemetrexed faʻalua togafitiga (187 tagata mamaʻi).

O le pito autu o le alualu i luma-leai se ola, ma ceritinib na sili atu le aoga. O le median alualu i luma-leai se ola ola o 16.6 masina ma le suesuega fualaau faasaina, faatusatusa i le 8.1 masina i le chemotherapy lima, mo se tulaga matautia o 0.55 (95% CI, 0.42-0.73; P <.0001).

O le aotelega tali fua faatatau sa lelei foi, i le 73% ma ceritinib ma 27% ma chemotherapy. Ole umi ole tali ile taimi ole 23.9 masina ile ceritinib male 11.1 masina ile platinum / pemetrexed. Ile taimi nei, o le aotelega o faʻamatalaga ola e tumau pea le matua. Ceritinib na faʻatagaina Breakthrough Therapy faʻatulagaina e le FDA, faʻatasi ai ma le faʻamuamua iloiloga mo muamua-laina togafitiga i lenei tagata maʻi tagata.

O le ASCEND-4 suʻesuʻega na suʻesuʻeina foi le tali atu i tagata mamaʻi ma e mafai ona fuaina le tutotonu o neula. O le fua faatatau na tali atu i totonu o le fale o le 57% ma le ceritinib, faatusatusa i le 22% ma le chemotherapy.

Ogaoga mea leaga na tutupu (AEs) na tupu i le 38% o tagata mamaʻi na togafitia i le ceritinib, ma AE e taʻitaʻia ai le faʻamutaina o le vailaʻau na tupu i le 12%. O faʻalavelave na mafua mai ile AE na vaʻaia ile 77% o tagata mamaʻi ole ceritinib, ma le 66% manaʻomia ai le faʻaititia o fualaʻau. Ole AE taatele ile vailaʻau ile ASCEND-4 e aofia ai le manava tata, niniva, puaʻi, lelava, ma tiga ole manava. "O le faʻamaonia i le asō o le isi laʻasaga i le atinaʻeina o Zykadia o se togafitiga filifiliga mo le ALK-positive metastatic NSCLC, ma aumaia ai lenei vailaʻau taua i tagata gasegase o loʻo iai pea manaʻoga," o le tala lea a le CEO Novartis Oncology, Bruno Strigini.

AASraw o le tagata tomai faapitoa gaosia o Ceritinib.

Faʻamolemole kiliki ii mo upusii faʻamatalaga: Faʻafesoʻotaʻi matou

 

Tusitaiala

[1] Mano H: Le EML4-ALK oncogene: faʻatatauina se mea manaʻomia tuputupu aʻe avetaʻavale i le kanesa o le tagata. Faʻataʻitaʻi Jpn Acad Ser B Phys Biol Sci. 2015; 91 (5): 193-201. faia: 10.2183 / pjab.91.193. [Faʻalauiloa: 25971657].

[2] Soria JC, Tan DS, Chiari R, Wu YL, Paz-Ares L, Wolf J, et al. (Mati 2017). "First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomized, tatala-igoa, vaega 3 suesuega". Lancet 389 (10072): 917–929.

[3] Xuan C, Gunduz V. "NSCLC MARKET - Faʻamatalaga o Vailaʻau i le Lalolagi atoa & Maketi Suʻesuʻega i le 2025". Atinaʻeina o Vailaau ma le Faaooina. Nu Novema – Tesema 2016.

[4] "Ua faamaonia e le FDA le Ceritinib mo le ALK-Positive Lung Cancer". Medscape Aperila 29, 2014.

[5] Au TH, Cavalieri CC, Stenehjem DD Ceritinib: O le faʻamuamua mo tagata faʻafomaʻi vailaʻau // Oncology fale faʻataʻitaʻi falemaʻi. - 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: Vaega I Suesuega o Ceritinib (LDK378) i Tagata Iapani Iapani ma Advanced, Anaplastic Lymphoma Kinase-Toe faʻatulagaina Laʻititi-Laʻitiiti-sela Kanesa Kanesa poʻo isi Tumors. J Thorac Oncol. 2015 Iulai; 10 (7): 1058-66. faia: 10.1097 / JTO.0000000000000566. [Faʻalauiloa: 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, Gray NS, Warmuth M : Faʻailogaina o le NVP-TAE684, o se malosi, filifilia, ma lelei le taofiofi o le NPM-ALK. Proc Natl Acad Sci US A. 2007 Ian 2; 104 (1): 270-5. Epub 2006 Tesema 21. [PubMed: 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, Gray NS, Steensma R, Wan Y, Jiang J, Chopiuk G, Li J, Gordon WP, Richmond W, Johnson K, Chang J, Groessl T, He YQ, Phimister A, Aycinena A, Lee CC, Bursulaya B, Karanewsky DS, Seidel HM, Harris JL, Michellys PY: Synthesis, fausaga-gaioiga faʻafesoʻotaʻiga, ma i le olaola lelei o le tala o le malosi ma filifilia filifilia anaplastic lymphoma kinase (ALK) taofi 5-chloro-N2- (2-isopropoxy-5-methyl-4- (piperidin-4-yl) phenyl) -N4- (2- (isopropylsulf onyl) phenyl) pyrimidine-2,4-diamine (LDK378) o loʻo i ai nei i le vaega 1 ma le vaega 2 falemaʻi tofotofoga. J Med Chem. 2013 Iulai 25; 56 (14): 5675-90. faia: 10.1021 / jm400402q Epub 2013 Jun 26. [PubMed: 23742252].

0 fiafia
Manatu 779

E mafai ona e fiafia foi

ua tapunia faamatalaga.