AASraw tsim NMN thiab NRC hmoov hauv qhov ntau!

Ceritinib

 

    1. Ceritinib Tau Pom Zoo Siv Hauv EU
    2. Ceritinib Piav Qhia
    3. Ceritinib Ua Haujlwm Li Cas Rau Kev Kho Mob NSCLC?
    4. Yuav Ua Li Cas Txog Ceritinib Kev Kho Mob Siv?
    5. Kev Khaws Ceritinib (LDK378) Li Cas?
    6. Ceritinib Qhov Teeb Meem Zoo Yog Dab Tsi?
    7. Lwm Yam Kev Pab Dab Tsi Ntawm Ceritinib Tau Qhia Tau Txog Hauv Kev Tshawb Fawb?
    8. Ceritinib Tau Txais Thawj Qhov Kab Ntawv FDA pom zoo rau Kab Mob Ntsws hauv ALK-Zoo

 

Ceritinib Tau Pom Zoo Siv Hauv EU

Ceritinib (CAS: 1032900-25-6) tau pom tias muaj txiaj ntsig zoo los kho cov neeg mob uas nws muaj mob ntau zuj zus lub sijhawm lossis tom qab tau kho nrog crizotinib thiab cov neeg tam sim no muaj kev xaiv kho mob tsawg heev, nrog rau cov neeg mob uas tsis tau kho ua ntej. Hais txog kev nyab xeeb, qhov tsis zoo nrog Ceritinib feem ntau pom tias tswj tau.

Lub Koom Haum Saib Xyuas Kev Noj Tshuaj nyob hauv Tebchaws Europe thiaj li txiav txim siab tias Ceritinib cov txiaj ntsig muaj txiaj ntsig ntau dua li nws cov kev pheej hmoo thiab pom zoo tias nws tau pom zoo rau kev siv hauv EU.

Ceritinib yog Ameslikas tau muab kev pom zoo 'muaj ntawv pom zoo' vim tias muaj ntau cov pov thawj los txog ntawm cov tshuaj. Raws li lub tuam txhab tau muab cov ntaub ntawv tsim nyog ntxiv, cov ntawv tso cai tau hloov pauv los ntawm cov xwm txheej rau kev pom zoo tag nrho.

Koj yuav tsum xav paub txog cov khoom no, Cia peb nyeem ntxiv infromation txog Ceritinib:

 

Ceritinib Piav Qhia

Ceritinib yog siv rau kev kho mob ntawm cov neeg laus uas muaj qhov mob pob khaus anaplastic linphoma kinase (ALK) -positive metastatic cov kab mob ntsws uas tsis yog mob hlwb (NSCLC) tom qab tsis ua tiav (theem nrab ntawm kev tawm tsam lossis tsis nkag siab) ntawm kev kho mob ua ntej. Kwv yees li 4% ntawm cov neeg mob NSCLC muaj cov roj teeb rov qab uas tsim cov fusion caj nruab nrab ntawm EML4 (echinoderm microtubule-txuam cov protein zoo li 4) thiab ALK (anaplastic lymphoma kinase), uas ua rau muaj kev ua haujlwm ntawm kinase uas ua rau carcinogenesis thiab zoo li tsav cov malignant phenotype.

Ceritinib tshaj tawm nws txoj kev kho mob tshwm sim los ntawm kev ua kom tsis txhob muaj kabmob autophosphorylation ntawm ALK, ALK-mediated phosphorylation ntawm cov roj ntsha qis hauv cov kabmob STAT3, thiab kev loj hlob ntawm ALK-qog mob hlwb. Tom qab kho nrog crizotinib (thawj cov tshuaj ALK inhibitor), cov qog feem ntau tsim tshuaj tiv thaiv vim muaj kev sib hloov hauv cov tseem ceeb ntawm "tus neeg zov me nyuam" cov seem ntawm cov enzyme. Qhov tshwm sim no tau coj mus rau kev tsim kho tshiab ntawm lub cim thib ob-tiam ALK inhibitors xws li ceritinib kom kov yeej cov khoom ua tsis taus. FDA tau pom zoo ceritinib nyob rau lub Plaub Hlis 2014 vim tias muaj qhov txawv lus txaus teb feem ntau (56%) ntawm cov qog ua tshuaj tiv thaiv kab mob thiab tau xaiv nws nrog chaw nyob hauv chaw ntsuag tshuaj.

 

Ceritinib Ua Haujlwm Li Cas Rau Kev Kho Mob NSCLC?

Ceritinib yog qhov xaiv thiab muaj zog inhibitor ntawm anaplastic lymphoma kinase (ALK). Nyob rau hauv ib txwm physiology, ALK haujlwm raws li theem pib tseem ceeb hauv kev txhim kho thiab kev ua haujlwm ntawm cov nqaij mos lub paj hlwb. Txawm li cas los xij, chromosomal hloov chaw thiab fusion muab nce mus rau ib daim ntawv oncogenic ntawm ALK uas tau cuam tshuam nyob rau hauv kev ua tiav ntawm NSCLC. Ceritinib yog li ua rau inhibit qhov enzyme mutated no thiab tso tseg kev loj hlob ntawm tes, thaum kawg tso tseg kev mob qog nqaij hlav.Because ceritinib suav tias yog kev kho mob qog nqaij hlav, kev tshuaj pom zoo los ntawm FDA yuav tsum txiav txim seb tus neeg mob yog neeg sib tw ntawm ceritinib. Qhov kev ntsuam xyuas no, tsim los ntawm Roche, yog VENTANA ALK (D5F3) CDx Assay thiab yog siv los txheeb xyuas ALK-zoo NSCLC cov neeg mob uas yuav tau txais txiaj ntsig los ntawm kev kho ceritinib.

 

Yuav Ua Li Cas Txog Ceritinib Kev Kho Mob Siv?

Ceritinib (LDK378) yog ib hom tshuaj siv los kho tus kabmob ntsws tsis yog mob ntsws uas tau kis mus rau lwm qhov ntawm lub cev thiab yog tus mob lumphoma kinase (ALK) zoo. Nws kuj tseem tau kawm txog kev kho mob lwm yam mob qog noj ntshav. Ceritinib thaiv cov protein ua los ntawm ALK caj ces. Qhov thaiv cov protein no yuav thaiv qhov kev loj hlob thiab nthuav tawm ntawm cov qog nqaij hlav cancer. Ceritinib yog ib hom tyrosine kinase inhibitor.

 

Ceritinib

 

Kev Khaws Ceritinib (LDK378) Li Cas?

Khaws Ceritinib (LDK378) rau hauv lub khob uas nws nkag los, kaw kom nruj, thiab ncav tsis cuag cov menyuam. Khaws nws ntawm chav sov thiab deb ntawm lub teeb, tshaj cua sov thiab noo noo (tsis nyob hauv chav dej).

Cov tshuaj tsis tau siv tshuaj yuav tsum tau muab pov tseg hauv txoj kev tshwj xeeb kom ntseeg tau tias cov tsiaj, menyuam yaus, thiab lwm tus neeg tsis tuaj yeem haus lawv. Txawm li cas los xij, koj yuav tsum tsis txhob tso Ceritinib (LDK378) rau hauv lub qhov viv. Hloov chaw, txoj hauv kev zoo tshaj plaws hauv kev muab koj cov tshuaj tshem tawm yog los ntawm kev siv tshuaj rov qab. Tham nrog koj tus kws muag tshuaj lossis tiv tauj koj lub chaw khaws khib nyiab / chaw khaws khoom ubno hauv zos kom paub txog cov haujlwm coj rov qab los ntawm koj thaj chaw. Saib cov FDA Kev Nyab Xeeb Kev Nyuaj Siab Tshuaj ntawm lub vev xaib txog ntaub ntawv ntxiv yog tias koj tsis muaj txoj haujlwm rov qab los.

Nws yog ib qho tseem ceeb rau kev noj txhua yam tshuaj kom tsis txhob pom thiab ncav cov menyuam yaus kom ntau lub thawv (xws li cov ntsiav tshuaj rau lub limtiam thiab cov neeg rau qhov muag tshuaj, cream, plhaw, thiab nqaum pa) tsis yog menyuam yaus thiab cov menyuam yaus tuaj yeem qhib tau yooj yim. Txhawm rau tiv thaiv cov me nyuam yaus kom txhob raug mob, nco ntsoov kaw lub hau kev ruaj ntseg thiab muab qhov chaw tso rau hauv qhov chaw nyab xeeb - ib qho uas tawm thiab deb thiab tawm ntawm lawv qhov muag thiab ncav cuag.

 

Ceritinib Qhov Teeb Meem Zoo Yog Dab Tsi? 

Cov khoom tseem ceeb uas yuav tsum nco ntsoov txog cov kev mob tshwm sim ntawm ceritinib:

People Cov neeg feem coob tsis muaj kev mob tshwm sim txhua yam.

Effects Cov kev mob tshwm sim feem ntau kwv yees nyob rau ntawm lawv qhov pib thiab ntev.

Effects Cov kev mob tshwm sim yuav luag txhua qhov thim rov qab thiab yuav ploj mus tom qab kev kho tiav.

Muaj ntau txoj hauv kev los pab txo qis lossis tiv thaiv kev phiv.

Tsis muaj qhov sib thooj ntawm qhov muaj lossis qhov tshwm sim ntawm kev mob tshwm sim thiab qhov zoo ntawm kev noj tshuaj.

 

Cov kev mob tshwm sim hauv qab no yog tshwm sim (tshwm sim ntau dua 30%) rau cov neeg mob noj ceritinib:

. Mob plab zawv

▪ Hemoglobin tsawg

▪ Nce rau cov nplooj siab enzymes

Ause xeev siab

Ntuav

▪ Nce rau hauv creatinine

▪ Mob plab

Igue Qaug zog

Uc Cov kua nplaum ntau zog

▪ Txav hauv phosphate

Tsis qab los noj mov

 

Cov kev mob tshwm sim no tsis tshua pom tshwm sim tshwm sim (kwv yees li 10-29%) ntawm cov neeg mob tau txais ceritinib:

Cem quav

▪ Lipase nce

▪ Mob txoj hlab pas (Lub plawv hlawv, dyspepsia, dysphagia)

Pob Ntxau

▪ Bilirubin (tag nrho) nce

Ib txoj kev mob tshwm sim hnyav heev, tab sis tsis tshua pom muaj tshwm sim li ceritinib yog mob ntsws (mob ntsws). Thaum cov kev mob tshwm sim no, feem ntau ua rau ua pa nyuaj nrog hnoos lossis ua npaws kub qis uas yuav tsum tau mus pw hauv tsev kho mob. Cov tsos mob tej zaum yuav zoo li cov tsos mob los ntawm mob ntsws. Hu rau koj tus kws kho mob tam sim ntawd yog tias koj muaj cov tsos mob tshiab lossis mob hnyav dua.

Lwm qhov kev txhaum loj tab sis tsis tshua pom tshwm sim ntawm ceritinib yog EKG hloov pauv. Tsis yog tag nrho cov kev mob tshwm sim muaj npe saum toj no. Qee qhov tsis tshua muaj tshwm sim (tshwm sim hauv tsawg dua 10% ntawm cov neeg mob) tsis muaj npe nyob ntawm no. Txawm li cas los xij, koj yuav tsum tau qhia koj tus kws saib xyuas kev noj qab haus huv yog tias koj muaj cov tsos mob txawv txawv.

 

Ceritinib

 

Lwm Yam Kev Pab Dab Tsi Ntawm Ceritinib Tau Qhia Tau Txog Hauv Kev Tshawb Fawb?

Hauv ob ntawm cov kev tshawb fawb no, suav nrog 303 cov neeg mob, cov tshuaj tsis tau piv nrog lwm txoj kev kho mob. Kev teb rau kev kho tau raug soj ntsuam siv kev ntsuas lub cev thiab cov qauv txheej txheem siv los ua cov qog, nrog cov lus teb tiav thaum tus neeg mob tsis muaj cov cim qhia tias muaj mob qog nqaij hlav. Hauv ib txoj kev tshawb nrhiav 56% ntawm cov neeg mob muab ceritinib (92 ntawm 163) tau txiav txim siab los ntawm cov kws kho mob kom pom tias muaj tag nrho lossis ib nrab teb rau cov tshuaj. Qhov nruab nrab ntev teb yog 8.3 hli. Hauv qhov kev tshawb nrhiav thib ob, tag nrho cov lus teb tau txais yog 41% (57 ntawm 140 tus neeg mob) thiab qhov nruab nrab ntev teb yog 10.6 lub hlis.

Hauv qhov kev tshawb fawb thib peb hauv 231 tus neeg mob, ceritinib piv nrog kev siv tshuaj kho mob (cov tshuaj los kho qog nqaij hlav cancer). Cov txiaj ntsig tau pom tias cov neeg mob muab ceritinib nyob rau nruab nrab ntawm 5.4 lub hlis yam tsis muaj lawv tus kab mob tsis zoo dua (kev vam meej-tsis ciaj sia taus) piv nrog 1.6 hli ntawm cov neeg mob muab cov tshuaj kho mob.

Ceritinib kuj tau pom tias muaj txiaj ntsig zoo ntawm kev kho cov neeg mob uas tsis tau kho ua ntej hauv kev tshawb fawb hauv 376 tus neeg mob. Cov neeg mob muab ceritinib nyob rau thaj tsam li ntawm 16.6 lub hlis yam tsis muaj lawv tus kab mob tsis zoo dua li piv rau 8.1 lub hlis ntawm cov neeg mob muab cov kws kho mob txheem.

 

Ceritinib Tau Txais Thawj Qhov Kab Ntawv FDA pom zoo rau Kab Mob Ntsws hauv ALK-Zoo

FDA tau nthuav dav kev pom zoo rau ceritinib. Tus neeg sawv cev tam sim no tau pom zoo ua thawj kab kev kho mob rau cov neeg mob uas mob metastatic, ALK-zoo, tsis yog-mob me-mob ntsws ntsws. Asmeskas Cov Khoom Noj thiab Tshuaj Yeeb Tshuaj (FDA) tau nthuav dav cov kev pom zoo rau ceritinibCov. Tus neeg sawv cev tam sim no tau pom zoo ua thawj kab kev kho mob rau cov neeg mob uas muaj metastatic, ALK-zoo, tsis yog-mob me-mob ntsws ntsws (NSCLC).

Ceritinib (LDK378) tau pom zoo yav dhau los hauv 2014 rau ALK-zoo metastatic NSCLC hauv cov neeg mob uas tau ua mus lossis lossis tsis nkag siab rau crizotinib. Tus neeg sawv cev yog xaiv xaiv qhov ncauj ALK inhibitor, nrog potency nees nkaum zaug uas ntawm crizotinib.

Lub ntsiab pov thawj tshiab yog nyob ntawm cov txiaj ntsig ASCEND-4 cov kev sim, cov txiaj ntsig tau luam tawm thaum Lub Ib Hlis Ntuj xyoo no hauv Lancet. Kev sim txiav txim siab 376 cov neeg mob nrog metastatic NSCLC nrog ALK rov kho dua rau ceritinib (189 tus neeg mob) lossis mus rau platinum-pemetrexed doublet kev kho mob (187 tus neeg mob).

Thawj qhov kawg yog kev vam meej tsis muaj kev vam meej, thiab ceritinib tau ua haujlwm zoo dua. Qhov nruab nrab ntawm kev vam meej tsis muaj txoj sia nyob ntev yog 16.6 lub hlis nrog kev tshawb nrhiav tshuaj, piv nrog 8.1 lub hlis ntawm kev siv tshuaj tua kab mob, rau qhov muaj xwm txheej txaus ntshai ntawm 0.55 (95% CI, 0.42–0.73; P <.0001).

Cov lus teb dav dav tau zoo dua, ntawm 73% nrog ceritinib thiab 27% nrog kev siv tshuaj lom neeg. Nruab nrab teb tau ntev yog 23.9 lub hlis nrog ceritinib thiab 11.1 lub hlis nrog platinum / pemetrexed. Txij ntawm no mus, tag nrho cov ntaub ntawv muaj sia nyob tseem tsis paub qab hau. Ceritinib tau tso cai rau Kev Tshawb Fawb Kev Tsim Kho los ntawm FDA, nrog rau kev tshuaj xyuas ua ntej rau kev kho thib ib hauv cov neeg mob no.

Txoj kev tshawb no ASCEND-4 kuj tseem tshuaj xyuas txog cov lus teb hauv cov neeg mob uas muaj feem cuam tshuam rau hauv cov hlab hlab siab. Cov lus teb hais txog kev teb rov qab yog 57% nrog ceritinib, piv nrog 22% nrog kev siv tshuaj lom neeg.

Cov kev mob hnyav tshwm sim (AEs) tshwm sim hauv 38% ntawm cov neeg mob kho nrog ceritinib, thiab AEs ua rau tsis cuam tshuam cov tshuaj tshwm sim hauv 12%. Kev cuam tshuam koob tshuaj ntau vim tias AEs tau pom hauv 77% ntawm cov neeg mob ceritinib, thiab 66% yuav tsum tau txhaj tshuaj. Cov tshuaj AE uas nquag muaj nrog rau cov tshuaj hauv ASCEND-4 suav nrog kev zawv plab, xeev siab, ntuav, nkees, thiab mob plab. Novartis Oncology tus thawj coj ntawm Bruno Strigini tau hais tias, "Kev pom zoo hnub no sawv cev rau kauj ruam tom ntej hauv kev txhim kho ntawm Zykadia raws li kev kho mob rau ALK-positive metastatic NSCLC, nqa cov tshuaj tseem ceeb no rau cov neeg mob uas qhov tseem xav tau,"

 

reference

[1] Mano H: EML4-ALK oncogene: tsom ntsoov kev tsav tsheb loj tseem ceeb hauv tib neeg mob qog noj ntshav. Proc Jpn Acad Ser B Lub Cev Biol Sci. Xyoo 2015; 91 (5): 193-201. doi: 10.2183 / pjab.91.193. [PubMed: 25971657].

[2] Soria JC, Tan DS, Chiari R, Wu YL, Paz-Ares L, Hma J, li al. (Lub Peb Hlis 2017). "First-line ceritinib tiv thaiv platinum-based chemotherapy hauv kev kho mob ALK-rov tsim kho tsis-me me ntawm lub ntsws mob ntsws (ASCEND-4): ib qho kev tsim kho, qhib-daim ntawv lo, theem 3 kawm". Kev Looj Mem. 389 (10072): 917–929.

[3] Xuan C, Gunduz V. “NSCLC LAG LUAM - Thoob Ntiaj Teb Kev Tshuaj Yeeb & Lag Luam Tshawb Xyuas Txog 2025”. Yeeb Tshuaj & Xa. No. Kaum Ib Hlis- Kaum Ob Hlis 2016.

[4] "FDA pom zoo Ceritinib rau Kab Mob Ntshav Tseem Ceeb ALK". Medscape. Plaub Hlis 29, 2014.

[5] Au TH, Cavalieri CC, Stenehjem DD Ceritinib: Ib qho pib rau tus kws muag tshuaj // Oncology lub tsev muag tshuaj xyaum. - 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: Ntu I Kawm Ceritinib (LDK378) hauv Japanese Neeg Mob nrog Kev Kawm Tshaj Lij, Anaplastic Lymphoma Kinase-Rearranged Tsis-Me-Lub cev mob ntsws lossis lwm yam nqaij hlav. J Thorac Oncol. 2015 Lub Xya Hli; 10 (7): 1058-66. doi: 10.1097 / JTO.0000000000000566. [PubMed: 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 : Txheeb xyuas ntawm NVP-TAE684, lub zog, xaiv, thiab ua tau zoo ntawm NPM-ALK. Proc Natl Acad Sci US A. 2007 Lub Ib Hlis 2; 104 (1): 270-5. Epub 2006 Dec 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, Grey NS, Steensma R, Wan Y, Jiang J, Chopiuk G, Li J, Gordon WP, Richmond W, Johnson K, Tseej J, Groessl T, Nws YQ, Phimister A, Aycinena A, Lee CC, Bursulaya B, Karanewsky DS, Seidel HM, Harris JL, Michellys PY: Kev sib txuam, kev tsim qauv-kev sib raug zoo, thiab hauv vivo ua tau zoo ntawm tus tshiab muaj hwj chim thiab xaiv anaplastic 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) tam sim no hauv ntu 1 thiab theem 2 chaw kho mob kev sim siab. J Med Chem. 2013 Jul 25; 56 (14): 5675-90. doi: 10.1021 / jm400402q. Epub 2013 Jun 26. [PubMed: 23742252].

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