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Cabozantinib

 

    1. Cabozantinib Tsanangudzo
    2. Cabozantinib Maitiro Ekuita
    3. Cabozantinib Side Mhedzisiro
    4. Dzazvino Kubudirira KweCabozantinib
    5. Cabozantinib Kurapa Kubudirira Nhau
    6. pfupiso

 

Cabozantinib tsananguro

Cabozantinib (CAS:849217-68-1) inoshandiswa kurapa kenza yeitsvo yakakwira, dzimwe nguva ichisanganiswa nemumwe mushonga unonzi nivolumab. Cabozantinib inoshandiswawo kurapa gomarara rechiropa muvanhu vakamborapwa ne sorafenib. Cabozantinib inoshandiswa kurapa kenza yehutachiona iyo yakapararira kune dzimwe nhengo dzomuviri. Cabozantinib inogona zvakare kushandiswa kune zvinangwa zvisina kunyorwa mune ino yekurapa gwara.

 

Cabozantinib Mechanism Yekuita

Targeted Therapis ndeye mhedzisiro yemakore zana ekutsvagira yakatsaurirwa kunzwisa mutsauko uripakati pemasero ekenza nemasero akajairwa. Parizvino, kurapwa kwegomarara kwakanangana nekuuraya nekukurumidza kunokamura masero nekuti chimwe chikamu checancer maseru ndechekuti dzinopatsanuka nekukurumidza. Nehurombo, mamwe emasero edu akajairika anopatsanuka nekukasira zvekare, zvichikonzeresa mhedzisiro.

Targeted therapy ndeyekutsanangura zvimwe zvikamu zvekenza masero. Masayendisiti anotarisa kusiyana kwakasiyana mumasero emukenza uye masero anowanzoitika. Idzi ruzivo runoshandiswa kugadzira chirongwa chinotarisirwa kurwisa makero ekenza pasina kutyisa masero ezvisikwa, izvo zvinotungamirira kune zvishoma migumisiro yechirwere. Mhando ipi neipi yekurapa inoratidzika inoshanda zvishoma zvakasiyana asi zvose zvinopesana nekwanisi yekenza yerineni kukura, kugovana, kugadzirisa uye / kana kutaurirana nemamwe masero.

Kune mhando dzakasiyana dzezvirwere zvinotarisirwa, zvinotsanangurwa mumitatu yakawanda. Zvimwe zvinotarisirwa kurapwa zvinotarisa pamusoro pezvikamu zvemukati uye basa rekenza yerineni. Mishonga inoshandiswa inoshandiswa inoshandisa maserolekisi maduku anogona kupinda muchitokisi nekuvhiringidza basa remasero, zvichiita kuti vafe. Kune mhando dzakawanda dzehutano hwakarongwa hunotarisa mukati memukati memasero. Zvimwe zvinotarirwa mishonga zvinotora zvinogamuchirwa zviri kunze kwekamuri. Mishonga inobata zvinogamuchirwa inozivikanwa seye monoclonal antibodies. Antiangiogenesis inhibitors inoshandiswa mumidziyo yeropa inopa oxygen kumasero, pakupedzisira ichiita kuti masero ave nenzara.

Cabozantinib chirwere chakanangwa chinotarisa uye chinosunga kune iyo tyrosine kinase receptors uye inhibits chiitiko cheakawanda tyrosine kinases, kusanganisira RET, MET, uye VEGF iri pamusoro pechitokisi. Nekusunga kune aya anogamuchira, cabozantinib inovhara nzira dzakakosha dzinosimudzira kupatsanurwa kwesero.

Kutsvakurudza kunoramba kuchicherechedza kuti zvipi zvekenza zvinogona kurapwa zvakanakisisa nemishonga inotarisirwa uye kuziva zvimwe zvinangwa zvemamwe marudzi ekenza.

 

Cabozantinib Migumisiro Yechiri

Tsvaga rubatsiro rwezvehutano rwekukurumidzira kana iwe une zviratidzo zvehutano hunoita: mikoko; kufema kwakaoma; kurira kwechiso chako, miromo, rurimi, kana huro.

Cabozantinib inogona kukonzera kuputika (gomba kana kubvarura) kana fistula (nzira isina kujairika) mukati medumbu rako kana ura. Dana chiremba wako kana iwe uine kurwadziwa kwakanyanya kwemudumbu, kana kana iwe uchinzwa kunge urikukachidzwa nekugwinha kana uchidya kana kunwa.

Dana chiremba wako kamwechete kana iwe uine:

▪ Kutemwa nemusoro zvakanyanya, kusaona zvakanaka, kurova muhuro kana nzeve dzako;

▪ Kurutsa, manyoka, kana kupatirwa zvakanyanya uye kuri kuenderera;

▪ Kuzvimba mumaoko ako, maoko, makumbo, kana tsoka;

▪ Kupwanya nyore kana kubuda ropa (kubuda ropa mumhino, kubuda ropa mazino, kubuda ropa kwakanyanya kumwedzi, kana kubuda kupi nekupi uko kusingaregi);

▪ Chituru chine ropa kana chekumira, kukosora nemamota ane ropa kana marutsi anotaridzika senge nzvimbo yekofi;

▪ Jaundice (yero yeganda kana maziso);

▪ Marwadzo, maronda, kubuda ropa, kana kuputika kwakanyanya muzvanza zvemaoko ako kana pasi petsoka dzako;

▪ Kuvhiringidzika, matambudziko ekufunga, kushaya simba, shanduko yekuona, kubata;

▪ Kunzwa-kureruka kunzwa, kunge kwaunogona kupfuura;

▪ Kurwadziwa pashaya kana chiveve, tsvuku kana kuzvimba matadza, mazino akasununguka, kana kunonoka kupora mushure mekuita mazino

▪ Low cell chena yeropa kuverenga –fivha, maronda emumuromo, maronda eganda, huro huro, chikosoro, kunetseka kufema;

▪ Adrenal gland matambudziko - kusvotwa, kurutsa, kuneta zvakanyanya, dzungu, kushaya simba, kufenda; kana

▪ Zviratidzo zvekurohwa kana kugwamba kweropa – kamwe kamwe chiveve kana kushaya simba kune rimwe divi remuviri wako, matambudziko nekuona kana kuenzanisa, kunetseka kutaura kana kunzwisisa zvinotaurwa kwauri, kurwadziwa pachipfuva, kunetseka kufema, kuzvimba kana kurwadziwa paruoko kana gumbo. .

Yako yemberi mizinga ye cabozantinib inogona kunonoka kana kumiswa zvachose kana uine mamwe mhedzisiro.

AASraw ndiye nyanzvi yekugadzira Cabozantinib.

Ndokumbirawo ubaye pano kuti uwane ruzivo Cont Cont us

 

Misungo yakajairika inogona kusanganisira:

▪ Kurwadziwa mudumbu, kuda kurutsa, kurutsa, kurasikirwa nechido, manyoka, kuzvimbirwa.

▪ Marwadzo, kutsvuka, kuzvimba, kana maronda mumuromo kana pahuro;

▪ Kunetseka kutaura, kuchinja mukuravira;

▪ Zviratidzo zvinotonhora semhino dzakazara, kuhotsira, huro, chikosoro;

▪ mapundu;

▪ Marwadzo munyama dzako, mapfupa, uye majoini;

▪ Kuongorora kushanda kwechiropa zvisina kujairika kana kumwe kuongorora kweropa;

▪ Kunzwa kuneta;

▪ Kuderedza uremu; kana

▪ Ruvara rwebvudzi ruchipenya.

Iri haisi rondedzero yakazara yemigumisiro uye vamwe vanogona kuitika. Dana chiremba wako kune mazano ekurapa nezvemigumisiro. Iwe unogona kuudza migumisiro yakaipa kune FDA pane 1-800-FDA-1088.

 

Dzazvino Kubudirira Kwe Cabozantinib 

Cabozantinib yakapihwa chinzvimbo chehunherera neUS Chikafu neDrug Administration (FDA) munaNovember 2010 uye munaKukadzi 2017.

Exelixis akaisa chikumbiro chitsva chemishonga kuDAA muhafu yekutanga yegore ra2012 uye nemusi waNovember 29, 2012 cabozantinib mukuumbwa kwayo kwemapuleti kwakapihwa mvumo yekushambadzira neUS FDA pasi pezita rekuti Cometriq yekurapa varwere vane kenza yemukaka medullary. yakatenderwa muEuropean Union nechinangwa chimwe chete muna2014.

Muna Kurume 2016 Exelixis akapihwa mvumo kune Ipsen kodzero dzepasirese (kunze kweUS, Canada, neJapan) kushambadza cabozantinib.

Exelixis 'Phase III mhedzisiro mhedzisiro yekuyedza mushonga mune renal kenza yakaburitswa muNEJM muna2015. MunaKubvumbi 2016 iyo FDA yakapa mvumo yekutengesa kuumbwa kwepiritsi seyechipiri mutsara wekurapa itsvo. kenza uye zvimwechetezvo zvakagamuchirwa muEuropean Union munaGunyana wegore iro.

Muna Zvita 2017, iyo FDA yakapa mvumo kune cabozantinib (Cabometyx, Exelixis, Inc.) yekurapa vanhu vane advanced renal cell carcinoma (RCC). Kubvumidzwa kwaive kwakavakirwa pane data kubva kuCABOSUN (NCT01835158), yakasarudzika, yakavhurika-yakashama-chikamu chikamu II multicenter kudzidza mune 157 vatori vechikamu vane wepakati uye varombo-njodzi vasati vambobatwa RCC.

MunaJanuary 2019, the FDA yakatendera cabozantinib (Cabometyx, Exelixis, Inc.) kune vanhu vane hepatocellular carcinoma (HCC) vakamborapwa ne sorafenib. Kubvumidzwa kwaive kwakavakirwa paECLESTIAL (NCT01908426), yakasarudzika (2: 1), yakapofomara-mbiri, inochengetedzwa ne placebo, multicenter kutongwa kwevatori vechikamu neHCC avo vakambogamuchira sorafenib uye vaine Mwana Pugh Kirasi Kukanganiswa kwechiropa.

Cabozantinib iri kuongororwa kuti ibudirire semushonga weiyo neurofibromatosis mhando 1.

Chikafu neDrug Administration (FDA) ichangobvumidza cabozantinib yekurapa hepatocellular carcinoma mune varwere vakambogamuchira sorafenib.

Cabozantinib ndeyemumuromo tyrosine kinases inhibitor yeMET, VEGFR, uye AXL. Receptor tyrosine kinases inotamba yakakosha mabasa mune ese akajairwa maseru mashandiro uye pathologic maitiro, anosanganisira oncogenesis, metastasis, tumor angiogenesis, uye tumor microenvelo yekuchengetedza.

Iyo FDA yakatanga kubvumidza cabozantinib yekurapwa kwema medullary chirwere chetachiona. Gare gare, iyo FDA yakabvumidza kushandiswa kwayo mu renal cell carcinoma.

 

Cabozantinib Kurapa Kubudirira Nhau 

Nhau 1: Cabozantinib Bata Yekutanga-Mutsetse Kurapa kwePamberi Renal Cell Carcinoma

Musi waZvita 19, 2017, iyo US Chikafu neDrug Administration (FDA) yakapa mvumo yenguva dzose kune cabozantinib (Cabometyx) yekurapa varwere vane advanced renal cell carcinoma (RCC).

Iyo FDA yakambobvumidza cabozantinib mu2016 kurapwa kwevarwere vane advanced RCC avo vakagamuchira pamberi antiangiogenic kurapwa. Kubvumidzwa kwanhasi kunopa kurapwa mune yekutanga-mutsara marongero.Cabozantinib

Iyi mvumo yaive yakavakirwa pane data kubva kuCABOSUN kutongwa, yakasarudzika, yakavhurika-yakashama-chikamu chikamu II multicenter kudzidza mune 157 varwere vane vepakati- uye varombo-njodzi yaimbove isina kurapwa RCC. Varwere vakagamuchira cabozantinib (n = 79) 60 mg muromo zuva nezuva kana sunitinib (Sutent) (n = 78) 50 mg muromo zuva nezuva (mavhiki e4 pakurapwa kunoteverwa nemavhiki e2 abva) kudzamara kuchirwara kwechirwere kana chepfu isingagamuchirike. Inofungidzirwa yepakati nepakati kufambira mberi-kwemahara kupona (sekuyedzwa nekapofumadzwa yakazvimirira radiology ongororo komiti) yevarwere vanotora cabozantinib yaive 8.6 mwedzi (95% nguva yekuvimba [CI] = 6.8-14.0) ichienzaniswa nemwedzi 5.3 (95% CI = 3.0-8.2) ye varwere vanotora sunitinib (hazard ratio = 0.48; 95% CI = 0.31-0.74; P = .0008).

Iwo anonyanya kutaurwa (≥ 25%) maitiro akashata muiyo cabozantinib kiriniki chirongwa chirwere, kurukutika, kuda kurutsa, kuda kudya, hypertension, palmar-plantar erythrodysesthesia, kuonda, kurutsa, dysgeusia, uye stomatitis.

Giredhi rinowanzoitika 3-4 maitiro akashata (≥ 5%) muvarwere vanobatwa necabozantinib paCABOSUN vaive neBP, chirwere, chirwere, hyponatremia, hypophosphatemia, palmar-plantar erythrodysesthesia, kuneta, ALT kuwedzera, kuderera kwechido, stomatitis, kurwadziwa, hypotension, uye syncope. Iyo yakakurudzirwa dhizaini ye cabozantinib ndeye 60 mg muromo, kamwe chete pazuva.

Cabozantinib inobvumidzwawo kurapwa kwe medullary cancer yegomarara uye inotengeswa pasi pezita rekutengeserana Cometriq. Cometriq neCabometyx vane mafomati akasiyana uye haachinji.

 

nyaya 2: Cabozantinib Bata Medullary Thyroid Kenza

Iyo FDA yakabvumidza cabozantinib (Cometriq) kurapa metastatic medullary cancer cancer (MTC) munaNovember 2012. Yaive yakavakirwa pamhedzisiro kubva kune wepasi rose, multicenter, randomized, maviri-bofu, kutongwa kutongwa kusanganisira 330 zvidzidzo. Vatori vechikamu vaifanirwa kuratidza chirwere chinofambira mberi mukati memwedzi gumi nemana vasati vapinda muchidzidzo, icho chakasimbiswa kuburikidza nekomiti yakazvimirira yekuongorora redhiyo kana chiremba anorapa.

Varwere vaisarudzika kuti vagamuchire chero cabozantinib 140 mg kana placebo nemuromo kamwe chete zuva nezuva kusvika pachirwere chinofambira mberi kana kusagadzikana kwehuturu. Randomization yaive yakasungwa zvinoenderana nezera <65 makore vs> makore 65 uye kushandiswa kwekare kwe tyrosine kinase inhibitor.Cabozantinib

Magumo ekutanga aive epamberi- yemahara kupona (PFS), chinangwa kupindura (OR), uye nguva yekupindura ichishandisa yakagadziridzwa RECIST maitiro. Varwere muboka re cabozantinib vaive nehurefu PFS zvichienzaniswa nevaya vanogamuchira placebo (P <.0001). Kunyanya, median PFS mune cabozantinib ruoko yaive 11.2 mwedzi uye wepakati PFS mune ye placebo ruoko yaive 4.0 mwedzi.

Varwere chete vanotora cabozantinib vakasangana nemhinduro shoma (27% vs 0; P <.0001). Uyezve, iyo yepakati nguva yeOO yaive 14.7 mwedzi yeavo vanorapwa nemushonga. Hapana misiyano yakakosha mukupona kwese yakaonekwa pakati pemaoko.

Mune 2019 meta- uye kuongorora kwehupfumi kuongorora kushandiswa kwecabozantinib uye vandetanib mune varwere veEngland National Health Service, Tappenden et al. Yakagumisa.

“Miedzo yakatarwa inoratidza kuti cabozantinib uye vandetanib vanovandudza PFS kupfuura placebo; zvisinei, zvakakosha OS mabhenefiti haana kuratidzwa. Ongororo yehupfumi inoratidza kuti mukati meiyo EU-mazita, ICERs [inowedzera mutengo-unoshanda zviyero] zvecabozantinib uye vandetanib iri> £ 138,000 paQALY (yakagadziridzwa mhando yehupenyu hupenyu gore) yakawanikwa. Mukati mevamiriri veEAB (European Union) vane ganhuriro, ICER ye vandetanib inotarisirwa kuve> £ 66,000 paQALY yakawanikwa. "

 

nyaya 3: Cabozantinib Bata Hepatocellular Carcinoma

Muna Ndira 2019, iyo FDA yakabvumidza cabozantinib mahwendefa evarwere vane hepatocellular carcinoma (HCC) yakamborapwa ne sorafenib. Kubvumidzwa kwaive kwakavakirwa pamhedzisiro kubva mukutongwa kweECLESTIAL

Mune iyo yakasarudzika (2: 1), yakapofomara-bofu, inodzorwa ne placebo, multicenter kuyedza, varwere vakasarudzika ku cabozantinib 60 mg muromo kamwe kamwe pazuva (n = 470) kana placebo (n = 237) kusvika panguva yechirwere kuwedzera kana kusingagamuchirwe chepfu.Cabozantinib

Yekupedzisira yekupedzisira yaive OS. PFS uye ORR, yakaongororwa nevanoongorora vachishandisa RECIST 1.1, yakaverengerwawo. Kushandiswa kweCabozantinib kwakabatana neiyo yepakati OS yemwedzi gumi (10.2% CI: 95-9.1) vs 12.0 mwedzi (8% CI: 95-6.8) yeavo vanogamuchira placebo (HR 9.4; 0.76% CI: 95, 0.63; P = .0.92). Median PFS yaive 0049 mwedzi (5.2-4.0) mune cabozantinib ruoko uchienzaniswa nemwedzi 5.5 (1.9-1.9) mune placebo ruoko (HR 1.9; 0.44% CI, 95, 0.36; P <.0.52). Iyo ORR yaive 001% (4% CI, 95, 2.3) mune avo vanotora cabozantinib vs 6.0% (0.4% CI, 95, 0.0) mune avo vanotora placebo.

Giredhi 3 kana 4 zviitiko zvakashata zvaive zvakakwirira kune varwere vaitora cabozantinib (68%) kupfuura kune avo vanotora placebo (36%).

Vanyori vekutongwa kweECLESTIAL vakapedzisa neanotevera: "Pakati pevarwere vakamborapwa hepatocellular carcinoma, kurapwa necabozantinib kwakakonzera kurarama kwenguva refu uye kufambira mberi-kusununguka pane placebo. Mwero wezviitiko zvegiredhi repamusoro muboka recabozantinib yaive zvakapetwa kaviri yakacherechedzwa muboka re placebo. ”

 

pfupiso

Cabozantinib is tyrosine kinase inhibitor inoshandiswa kurapa yakakwira renal cell carcinoma, hepatocellular carcinoma, uye medullary cancer kenza. Cabozantinib yakatanga kubvumidzwa mu2012 uye isiri-yakasarudzika tyrosine kinase inhibitor. Pakutanga yakatenderwa muUS pasi pezita rekuti Cometriq, iyo inoratidzirwa yekurapa metastatic medullary thyroid cancer.Cabometyx) yakatenderwa kurapwa kweiyo yepamusoro renal cell carcinoma, uye iyo imwecheteyo fomendi yakawana mvumo yekuwedzera muUS neCanada muna2019 yekurapa hepatocellular carcinoma mune vakamborapwa varwere.

AASraw ndiye nyanzvi yekugadzira Cabozantinib.

Ndokumbirawo ubaye pano kuti uwane ruzivo Cont Cont us

 

Reference

[1] Choueiri TK, Escudier B, Powles T, et al. Cabozantinib maringe everolimus mune yepamusoro renal cell carcinoma (METEOR): mhedzisiro mhedzisiro kubva kune yakasarudzika, yakavhurika-yakashama, chikamu chechitatu kutongwa. Lancet Oncol. 3; 2016: 17-917.

[2] Tappenden P, Carroll C, Hamilton J, uye al. Cabozantinib uye vandetanib yechinhu chisingachinjike munharaunda yemhando yepamusoro kana metastatic medullary cancer kenza. Hutano Technol Ongorora. 2019; 23: 1-144.

[3] George DJ, Hessel C, Halabi S, et al. Cabozantinib maringe nezuvaitinib yevasina kurapwa varwere vane renal cell carcinoma yepakati kana isina njodzi njodzi: subgroup kuongororwa kweAlliance A031203 CABOSUN kutongwa. Oncologist. 2019; 24: 1-5.

[4] Kurzrock R, Sherman SI, Bhora DW, Forastiere AA, Cohen RB, Mehra R, Pfister DG, Cohen EE, Janisch L, Nauling F, Hong DS, Ng CS, Ye L, Gagel RF, Frye J, Muller T, Ratain MJ , Salgia R: Chiitiko cheXL184 (Cabozantinib), yemumuromo tyrosine kinase inhibitor, mune varwere vane medullary cancer yekenza. J Clin Oncol. 2011 Jul 1; 29 (19): 2660-6. doi: 10.1200 / JCO.2010.32.4145. Epub 2011 Chivabvu 23.

[5] Abou-Alfa GK, Meyer T, Cheng AL, uye al. Cabozantinib mune varwere vane yepamusoro uye inofambira mberi hepatocellular carcinoma. N Engl J Med. 2018; 379: 54-63.

[6] US Kudya neDrug Administration. FDA inobvumidza cabozantinib ye hepatocellular carcinoma. Inowanikwa pa: https://www.fda.gov/drugs/fda-approves-cabozantinib-hepatocellular-carcinoma Yakasvika muna Nyamavhuvhu 28, 2019.

[7] Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, Qian F, Chu F, Bentzien F, Cancilla B, Orf J, Iwe A, Laird AD, Engst S, Lee L, Lesch J, Chou YC , Joly AH: Cabozantinib (XL184), inoverengeka MET uye VEGFR2 inhibitor, panguva imwe chete inodzvinyirira metastasis, angiogenesis, uye bundu kukura. Mol Kenza Ther. 2011 Zvita; 10 (12): 2298-308. doi: 10.1158 / 1535-7163.MCT-11-0264. Epub 2011 Sep 16.

[8] "Kenza yegomarara mushonga cabozantinib inowedzera PFS". Yakachengetedzwa kubva kune yekutanga pane 2012-04-02. Yakadzorerwa 24 Gumiguru 2011.

[9] "Cabozantinib Orphan Zvinodhaka Zvinodomwa uye Mvumo". US Kudya neDrug Administration (FDA). 29 Mbudzi 2010. Yakadzorerwa 11 Mbudzi 2020.

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