ALK-Yakanaka Lung Cancer Zvinodhaka "Ceritinib (LDK378)" - AASraw
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Ceritinib

 

    1. Ceritinib Yakagamuchirwa Kuti Ishandiswe muEU
    2. Ceritinib Tsananguro
    3. Ceritinib Inoshanda Sei Kurapa NSCLC?
    4. Zvakadii nezveCeritinib Zvekushandisa Zvekurapa?
    5. Sei Kuchengeta Ceritinib (LDK378)?
    6. Ndezvipi Zvinokuvadza zveCeritinib?
    7. Ndezvipi Zvimwe Zvakanakira Ceritinib Zvave Zvichiratidzwa MuZvidzidzo?
    8. Ceritinib Inowana Yekutanga-Mutsara FDA Kubvumidzwa kwe ALK-Yakanaka Lung Cancer

 

Ceritinib Yakagamuchirwa Yekushandisa muEU

Ceritinib (CAS: 1032900-25-6) yakaratidzirwa kuve inoshanda pakurapa varwere vane chirwere chakafambira mberi panguva kana pfupi mushure mekurapwa crizotinib uye ndiani parizvino ane nzira shoma dzekurapa, pamwe nevarwere vasina kumborapwa kare. Nezve chengetedzo, mhedzisiro yakaipa neCeritinib kazhinji yaitaridzika kunge inokwanisika.

European Medicines Agency saka yakafunga kuti mabhenefiti aCeritinib akakura kupfuura njodzi dzayo uye vakakurudzira kuti ibvumidzwe kuti ishandiswe muEU.

Ceritinib akambopihwa 'mvumo yekutenderwa' nekuti paive nehumwe humbowo hunouya nezve mushonga. Sezvo kambani yakapa ruzivo rwakawedzerwa rwakakodzera, mvumo yacho yakachinjwa kubva pane zvinoenderana nekugamuchirwa zvizere.

Iwe unofanirwa kuda kuziva nezve ichi chigadzirwa, Ngativerengei zvimwe infromation nezve Ceritinib:

 

Ceritinib Tsananguro

Ceritinib inoshandiswa pakurapa kwevakuru vane anaplastic lymphoma kinase (ALK) -inosimudzira metastatic isina-diki kenza yemapapu kenza (NSCLC) zvichitevera kutadza (kwechipiri kuramba kana kusagadzikana) kwepamberi crizotinib kurapa. Vanenge 4% yevarwere vane NSCLC vane chromosomal rearrangement inogadzira fusion gene pakati peEML4 (echinoderm microtubule-inosanganisirwa mapuroteni-senge 4) uye ALK (anaplastic lymphoma kinase), iyo inokonzeresa kuita kwechi kinase chiitiko chinopa kune carcinogenesis uye inoita kunge inotyaira iyo yakaipa phenotype.

Ceritinib ine simba rayo rekurapa nekudzivirira autophosphorylation yeALK, ALK-yakagadziriswa phosphorylation yepasi yekuratidzira protein STAT3, uye kuwanda kwema ALK-anoenderana nekenza maseru emukenza. Kutevera kurapwa ne crizotinib (chizvarwa chekutanga ALK inhibitor), mazhinji mamota anovandudza kusagadzikana kwemishonga nekuda kwekuchinja mune akakosha e "murindi wesuo" masara enzyme. Izvi zvakaitika zvakakonzera kukura kweruzivo rwechipiri-chizvarwa ALK inhibitors senge ceritinib kukunda crizotinib kuramba. Iyo FDA yakabvumidza ceritinib muna Kubvumbi 2014 nekuda kwekushamisa kwepamusoro kwehuwandu hwekupindura (56%) yakanangana nemamota anodzivirira crizotinib uye akaisarudzira nenzvimbo yenherera yemishonga.

 

Ceritinib Inoshanda Sei Kurapa NSCLC?

Ceritinib inosarudza uye ine simba inhibitor yeaplastic lymphoma kinase (ALK). Mune zvakajairika physiology, ALK mabasa sedanho rakakosha mukuvandudza uye mashandiro ehurongwa hwetsinga. Nekudaro, chromosomal translocation uye fusion zvinomutsa imwe oncogenic fomu ye ALK iyo yakave yakabatanidzwa mukufambira mberi kweNSCLC. Ceritinib nokudaro inoshanda kudzivirira iyi enzyme yakachinja uye kumisa kuwanda kwesero, pakupedzisira ichimisa kufambira mberi kwekenza Nekuda kwekuti ceritinib inoonekwa seyakanangana nekenza yekurapa, bvunzo yeDAA-inotenderwa inofanirwa kuona kuti ndevapi varwere vari kukwikwidza ceritinib. Bvunzo iyi, yakagadziridzwa naRoche, ndiyo VENTANA ALK (D5F3) CDx Assay uye inoshandiswa kuzivisa ALK-positive NSCLC varwere vangazobatsirwa neceritinib kurapwa.

AASraw ndiye nyanzvi yekugadzira Ceritinib.

Ndokumbirawo ubaye pano kuti uwane ruzivo Cont Cont us

 

Zvakadii nezveCeritinib Zvekushandisa Zvekurapa?

Ceritinib (LDK378) mushonga unoshandiswa kurapa isiri-diki kenza yemapapu kenza yakapararira kune dzimwe nhengo dzemuviri uye ine aplastic lymphoma kinase (ALK) yakanaka. Iri zvakare kudzidziswa mukurapa kwemamwe marudzi ekenza. Ceritinib inovhara protein inogadzirwa neALK geni. Kuvhara protein iyi kunogona kumisa kukura uye kupararira kwemasero ekenza. Ceritinib rudzi rwe tyrosine kinase inhibitor.

 

Ceritinib

 

Sei Kuchengeta Ceritinib (LDK378)?

Chengeta Ceritinib (LDK378) mumudziyo iyo yakauya mukati, yakavharwa zvakasimba, uye isingasviki nevana. Zvichengetedze pane tembiricha yekamuri uye kure nechiedza, kupisa kwakanyanya uye hunyoro (kwete muchimbuzi).

Mishonga isingadiwe inofanirwa kuraswa nenzira dzakakosha kuona kuti zvipfuyo, vana, nevamwe vanhu havagone kuzvidya. Zvisinei, haufanire kuburitsa Ceritinib (LDK378) pasi pechimbuzi. Panzvimbo iyoyo, nzira yakanakisa yekurasa mishonga yako ndeye chirongwa chekudzosa-mushonga. Taura nachiremba wako kana kuti taura nedhipatimendi rako remarara / rekudzokorora kuti udzidze nezve zvirongwa zvekudzosa munharaunda yako. Ona iyo FDA's Safe Disposal yeMedicine webhusaiti kuti uwane rumwe ruzivo kana iwe usina mukana wekutora kudzoka chirongwa.

Zvakakosha kuchengetedza mishonga yose isingaoneki uye kusvika kune vana semiti yakawanda (yakadai sepiritsi yevhiki nevhiki uye yeavo madonhe emeso, makemikari, makanda, uye inhalers) haisi vana vasingagoneki uye vana vaduku vanogona kuvhura nyore nyore. Kuchengetedza vana vaduku kubva muchetura, nguva dzose chengetedza kuchengetedzwa kwekuchengetedza uye pakarepo ita mishonga munzvimbo yakachengeteka - imwe yakasimuka uye kure uye isati yavaona uye inosvika.

 

Ndezvipi Zvinokuvadza zveCeritinib? 

Zvinhu zvakakosha zvekurangarira nezve iyo mhedzisiro mhedzisiro ceritinib:

Vanhu vazhinji havasati vasangana nemhedzisiro.

▪ Mhedzisiro inowanzo fungidzirwa maererano nekutanga uye hurefu hwayo.

▪ Mhedzisiro inowanzochinja uye ichaenda kana kurapwa kwapera.

▪ Pane nzira dzakawanda dzekubatsira kudzikisa kana kudzivirira mhedzisiro.

▪ Hapana hukama pakati pekuvapo kana kuomarara kwemhedzisiro pamwe nekushanda kwemushonga.

 

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

▪ Manyoka

▪ Hemoglobin yakaderera

▪ Wedzera ma enzymes echiropa

▪ Kusvotwa

▪ Kurutsa

▪ Wedzera mu creatinine

▪ Kurwadziwa mudumbu

▪ Kuneta

▪ Glucose yakawedzera

▪ Kuderera mu phosphate

▪ Kuderedza kudya

AASraw ndiye nyanzvi yekugadzira Ceritinib.

Ndokumbirawo ubaye pano kuti uwane ruzivo Cont Cont us

 

Iyi mhedzisiro haina kujairika mhedzisiro (inoitika mune ingangoita 10-29%) yevarwere vanogamuchira ceritinib:

▪ Kuzvimbirwa

▪ Lipase yakawedzera

▪ Esophageal disorder (Moyo unopisa, dyspepsia, dysphagia)

▪ Mapundu

▪ Bilirubin (yakazara) yakawedzera

Chinhu chakakomba, asi chisingawanzoitika pamhedzisiro ceritinib pneumonitis (kuzvimba kwemapapu). Kana iri divi mhedzisiro rikaitika, raiwanzoperekedzwa nekufema kunetseka nekukosora kana fivha yepasi-gorosi inoda kuchipatara. Zviratidzo zvinogona kunge zvakafanana nezviratidzo kubva mukenza yemapapu. Bata wako mupi wezvehutano ipapo kana iwe uine chero nyowani kana kuwedzera zviratidzo.

Chimwe chakakomba asi chisingajairiki mhedzisiro mhedzisiro ye cititinib ndeye EKG shanduko. Haasi ese mhedzisiro akanyorwa pamusoro. Zvimwe izvo zvisingawanzoitika (zvinoitika mune isingasviki gumi muzana yevarwere) hazvina kunyorwa pano. Nekudaro, iwe unofanirwa kugara uchizivisa mupi wako wezvehutano kana iwe uchinge uchinge uchinge uchinge uchinge uchinge uchinge uchinge uchinge uchinge uchiona zviratidzo

 

Ceritinib

 

Ndezvipi Zvimwe Zvakanakira Ceritinib Zvave Zvichiratidzwa MuZvidzidzo?

Mune maviri ezvidzidzo izvi, zvinosanganisira 303 varwere, mushonga wacho hauna kuenzaniswa nechero kumwe kurapwa. Mhinduro kurapa yakaongororwa uchishandisa zviyero zvemuviri uye zviyero zvakamisikidzwa zvinoshandiswa kumatumbu akasimba, nemhinduro yakazara iri apo murwere anga asisina zviratidzo zvekenza. Mune kumwe kuongorora 56% yevarwere vakapihwa ceritinib (92 yegumi nematanhatu) vakafungidzirwa navanachiremba vanorapa kuti varatidze mhinduro yakakwana kana shoma kumushonga. Ivhareji kureba kwemhinduro yaive 163 mwedzi. Muchidzidzo chechipiri, chiyero chekupindura chaive 8.3% (41 yevarwere zana nemakumi mana) uye paavhareji kureba kwemhinduro yaive mwedzi 57.

Muchidzidzo chechitatu muvarwere makumi maviri nevaviri, ceritinib yaifananidzwa neyakajairwa chemotherapy (mishonga yekurapa cancer). Mhedzisiro yakaratidza kuti varwere vakapihwa ceritinib vakararama kwemavhareji emwedzi 231 pasina chirwere chavo chichiwedzera (kufambira mberi-kusununguka) kana ichienzaniswa ne5.4 mwedzi yevarwere vanopihwa standard chemotherapy.

Ceritinib yakaratidzirwawo kuva inoshanda pakurapa varwere avo vasina kubatwa kare muchidzidzo muvarwere mazana matatu nemakumi matanhatu nenomwe. Varwere vakapiwa ceritinib vakararama kwemavhareji emwedzi 376 pasina chirwere chavo kuchinyanya kuenzaniswa kana 16.6 mwedzi mukati mevarwere vanopihwa standard chemotherapy.

 

Ceritinib Inowana Yekutanga-Mutsara FDA Kubvumidzwa kwe ALK-Yakanaka Lung Cancer

Iyo FDA yakawedzera kubvumidzwa kwe ceritinib. Iyo mumiriri ikozvino inogamuchirwa seyekutanga-kurapwa kurapwa mune varwere vane metastatic, ALK-positi, isiri-diki-sero kenza yemapapu kenza. IU.S. Chikafu neDrug Administration (FDA) yakawedzera iyo kubvumirwa kwecititi. Iyo mumiriri ikozvino inogamuchirwa seyekutanga-kurapwa kurapwa mune varwere vane metastatic, ALK-positi, isiri-diki-sero kenza yemapapu kenza (NSCLC).

Ceritinib (LDK378) yakambotenderwa muna2014 yeAlk-positive metastatic NSCLC kune varwere vaive vafambira mberi kana vaisashivirira crizotinib. Iyo mumiririri inosarudzwa yemumuromo ALK inhibitor, ine potency makumi maviri yakapetwa kaiyo crizotinib.

Icho chiratidzo chitsva chakavakirwa pamhedzisiro yeASCEND-4 kuyedzwa, mhedzisiro yacho yakaburitswa muna Ndira wegore rino muLancet. Muedzo wakarongedza 376 varwere vane metastatic NSCLC ine ALK rearrangements kune chero ceritinib (189 varwere) kana kune platinamu-pemetrexed doublet therapy (187 varwere).

Iyo yekupedzisira yekupedzisira yaive yekuenderera-isina kupona, uye ceritinib yainyanya kushanda. Iyo yepakati yekufambira mberi-yemahara kupona yaive 16.6 mwedzi nemushonga wekudzidza, uchienzaniswa nemwedzi.8.1 mune chemotherapy ruoko, kune ngozi yengozi ye0.55 (95% CI, 0.42-0.73; P <.0001).

Iyo yakazara yekupindura mwero yaive zvakare iri nani, pa73% ine ceritinib uye 27% ine chemotherapy. Nguva yekupindurwa yepakati yaive 23.9 mwedzi ine ceritinib uye 11.1 mwedzi ine platinamu / pemetrexed. Parizvino, data rekupona rese rinoramba riri diki. Ceritinib yakapihwa Breakthrough Therapy kudomwa neiyo FDA, pamwe nekutanga kuongorora kweyekutanga-line kurapa mune ino murwere huwandu.

Iyo ASCEND-4 yekudzidza yakaongororawo mhinduro dzemitero muvarwere vane zviyero zvepakati zvehurongwa hwemitsipa Iyo yakasimbiswa yekusaita mhinduro mhinduro yaive 57% ine ceritinib, ichienzaniswa ne22% nekemotherapy.

Zviitiko zvakakomba zvakashata (AEs) zvakaitika mu38% yevarwere vanobatwa neceritinib, uye maAEs anotungamira mukumiswa kwechirwere ichi chakaitika mu12%. Dose kukanganiswa nekuda kweAEs kwakaonekwa mu77% yevarwere ceritinib, uye 66% yaida kudzikisira dosi. MaAEs anowanzozivikanwa nemushonga muASCEND-4 aisanganisira manyoka, kusvotwa, kurutsa, kuneta, uye kurwadziwa nemudumbu. "Kubvumidzwa kwanhasi kunomiririra danho rinotevera mukuvandudzwa kweZykadia senzira yekurapa yeAlk-positive metastatic NSCLC, ichiunza mushonga uyu wakakosha kune varwere pane kudiwa kuchiripo," akadaro Executive Officer weNovartis Oncology, Bruno Strigini, muchinyorwa chakaburitswa.

AASraw ndiye nyanzvi yekugadzira Ceritinib.

Ndokumbirawo ubaye pano kuti uwane ruzivo Cont Cont us

 

Reference

[1] Mano H: Iyo EML4-ALK oncogene: kunongedza yakakosha yekukura mutyairi mukenza yemunhu. Proc Jpn Acad Ser B Panyama Biol Sci. 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, Wolf J, uye al. (Kurume 2017). "Yekutanga-mutsara ceritinib maringe neplatinamu-yakavakirwa chemotherapy mune yakakwira ALK-yakagadziriswazve isiri-diki-sero kenza yemapapu (ASCEND-4): yakasarudzika, yakavhurika-label, chikamu chechitatu kudzidza". Lancet. 3 (389): 10072–917.

[3] Xuan C, Gunduz V. "NSCLC MARKET - Global Drug Forecast & Kuongorora kweMusika kusvika 2025". Kubudirira Kwemishonga & Dhirivhari. Kwete. Mbudzi – Zvita 2016.

[4] "FDA Inotendera Ceritinib yeAlk-Positive Lung Cancer". Medscape. Kubvumbi 29, 2014.

[5] Au TH, Cavalieri CC, Stenehjem DD Ceritinib: Iyo yekutanga yevarapi vemishonga // Oncology chemishonga tsika. - 2017. - Vhor. 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: Chikamu I Kudzidza kweCeritinib (LDK378) muvarwere veJapan vane Advanced, Anaplastic Lymphoma Kinase-Yakagadzirwazve Isiri-Diki-Cell Lung Cancer kana Mamwe Matumbo. J Thorac Oncol. 2015 Jul; 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, Zuva F, Schultz PG, Grey NS, Warmuth M : Kuzivikanwa kweNVP-TAE684, ine simba, inosarudza, uye inoshanda inhibitor yeNPM-ALK. Proc Natl Acad Sci US A. 2007 Jan 2; 104 (1): 270-5. Epub 2006 Zvita 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, Chang J, Groessl T, Iye YQ, Phimister A, Aycinena A, Lee CC, Bursulaya B, Karanewsky DS, Seidel HM, Harris JL, Michellys PY: Synthesis, mamiriro-ehukama hukama, uye mu vivo kushanda kweruzivo rune simba uye inosarudza 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) parizvino muchikamu 1 uye chikamu 2 kiriniki miedzo. J Med Chem. 2013 Jul 25; 56 (14): 5675-90. doi: 10.1021 / jm400402q. Epub 2013 Jun 26. [PubMed: 23742252].

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