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Kabozantinib

 

    1. Kufotokozera kwa Cabozantinib
    2. Njira ya Cabozantinib Ya Ntchito
    3. Zotsatira za Cabozantinib
    4. Kukula Kwaposachedwa Kwa Cabozantinib
    5. Nkhani Za Kuchiza kwa Cabozantinib Nkhani Zabwino
    6. Chidule

 

Kabozantinib Kufotokozera

Cabozantinib (CAS:849217-68-1) amagwiritsidwa ntchito pochiza khansa yapakati ya impso, nthawi zina kuphatikiza ndi mankhwala ena otchedwa nivolumab. Cabozantinib imagwiritsidwanso ntchito pochiza khansa ya chiwindi mwa anthu omwe adathandizidwapo kale ndi sorafenib. Cabozantinib amagwiritsidwa ntchito pochiza khansa ya chithokomiro yomwe yafalikira mbali zina za thupi. Cabozantinib itha kugwiritsidwanso ntchito pazinthu zomwe sizinalembedwe pamankhwalawa.

 

Kabozantinib Njira Zamachitidwe

Chithandizo chotsata ndichotsatira cha zaka pafupifupi 100 za kafukufuku woperekedwa kuti amvetsetse kusiyana pakati pa maselo a khansa ndi maselo abwinobwino. Mpaka pano, chithandizo cha khansa chimangoyang'ana pakupha magawo omwe amagawa mwachangu chifukwa gawo limodzi la maselo a khansa ndikuti amagawika mwachangu. Tsoka ilo, maselo athu abwinobwino amagawikanso mwachangu, ndikupangitsa zotsatirapo zingapo.

Thandizo lachidule ndilokulongosola zina mwa maselo a kansa. Asayansi amafufuza kusiyana komwe kumakhala ndi maselo a khansa komanso maselo ochibadwa. Chidziwitso chimenechi chikugwiritsidwa ntchito poyambitsa chithandizo chowopsya kuti chiwononge maselo a khansa popanda kuwononga maselo ochibadwa, motsogolere ku zotsatira zochepa. Njira iliyonse ya mankhwala opatsirana imagwira ntchito mosiyana koma zonse zimalepheretsa mphamvu ya khansa kukula, kugawa, kukonza ndi / kapena kuyankhulana ndi maselo ena.

Pali mitundu yosiyanasiyana ya mankhwala okhudzidwa, omwe amatchulidwa muzigawo zitatu. Zina zothandizira zamankhwala zimaganiziranso zigawo za mkati ndi ntchito ya selo ya khansa. Njira zochiritsirazo zimagwiritsa ntchito mamolekyu ang'onoang'ono omwe angalowe mu selo ndi kusokoneza ntchito ya maselo, kuwapangitsa kufa. Pali mitundu yambiri ya mankhwala opatsirana omwe amayang'ana mkati mwa maselo. Zina zogwiritsidwa ntchito ndi zothandizira zakulandila zomwe zili kunja kwa selo. Mankhwala omwe amalimbana ndi mapiritsi amadziwikanso amadzimadzi a monoclonal. Antiangiogenesis inhibitors amayang'ana mitsempha ya magazi yomwe imapereka mpweya ku maselo, ndipo pamapeto pake amachititsa maselo kukhala ndi njala.

Cabozantinib ndi mankhwala omwe amalimbana nawo tyrosine kinase receptors ndi inhibits zochitika za angapo tyrosine kinases, kuphatikiza RET, MET, ndi VEGF panja pa selo. Mwa kumangiriza kuzilandira izi, cabozantinib imatseka njira zofunika zomwe zimathandizira kugawanika kwama cell.

Kafukufuku akupitiriza kuzindikira kuti ndi khansa iti yomwe ingaperekedwe bwino ndi mankhwala othandizira komanso kupeza zowonjezereka za mitundu ina ya khansa.

 

Kabozantinib Zotsatira Zotsatira

Pezani chithandizo chamankhwala chodzidzimutsa ngati muli ndi zizindikiro zotsutsa: ming†™ oma; kupuma kovuta; Kutupa kwa nkhope, milomo, lilime, kapena mmero.

Cabozantinib itha kubowola (dzenje kapena kung'ambika) kapena fistula (njira yachilendo) m'mimba mwanu kapena m'matumbo. Itanani dokotala wanu ngati mukumva kupweteka kwambiri m'mimba, kapena ngati mukumva ngati mukutsamwa ndikudya mano mukamadya kapena kumwa.

Itanani dokotala wanu mwamsanga ngati muli:

▪ Mutu wopweteka kwambiri, kusawona bwino, kukupweteketsani m'khosi kapena m'makutu;

▪ Kusanza, kutsekula m'mimba, kapena kudzimbidwa komwe kumakhala koopsa komanso kosalekeza;

▪ Kutupa m'manja, mikono, miyendo, kapena mapazi;

▪ Kutunduza kapena kutuluka magazi mosavuta (kutuluka magazi m'mphuno, kutuluka magazi m'kamwa, kutuluka kwambiri msambo, kapena kutuluka magazi komwe sikungaleke)

▪ Zimbudzi zamagazi kapena zochedwa, kutsokomola ndi ntchofu zamagazi kapena masanzi omwe amawoneka ngati malo a khofi;

▪ Jaundice (chikasu chachikopa kapena maso);

▪ Zilonda, zotupa, magazi, kapena zotupa zazikulu m'manja mwanu kapena m'mapazi anu;

▪ Kusokonezeka, kuganiza molakwika, kufooka, kusintha masomphenya, kulanda;

▪ Kumverera kopepuka, ngati momwe mungathere;

▪ Kuwawa kwa nsagwada kapena dzanzi, chingamu chofiira kapena chotupa, mano otuluka, kapena kuchira pang'onopang'ono mukamaliza mano;

▪ Maselo oyera amagazi ochepa - kutentha thupi, zilonda za mkamwa, zilonda pakhungu, zilonda zapakhosi, chifuwa, kupuma movutikira;

▪ Mavuto a minyewa ya Adrenal – nseru, kusanza, kutopa kwambiri, chizungulire, kufooka, kukomoka; kapena

▪ Zizindikiro za sitiroko kapena magazi oundana-kufooka mwadzidzidzi kapena kufooka mbali imodzi ya thupi lanu, mavuto a kuona bwino, kulephera kuyankhula kapena kumvetsetsa zomwe akunenedwa, kupweteka pachifuwa, kupuma movutikira, kutupa kapena kupweteka kwa mkono kapena mwendo .

Mlingo wanu wamtsogolo wa cabozantinib ukhoza kuchedwa kapena kutha kosatha ngati mungakhale ndi zovuta zina.

AASraw ndiye katswiri wopanga Cabozantinib.

Chonde dinani apa kuti mumve zambiri: Ochezera ife

 

Zotsatira zowonjezereka zingaphatikizepo:

▪ Kumva m'mimba, nseru, kusanza, kusowa njala, kutsegula m'mimba, kudzimbidwa;

▪ Kupweteka, kufiira, kutupa, kapena zilonda mkamwa kapena kukhosi;

▪ Kulephera kulankhula, kusintha kukoma;

▪ Zizindikiro zozizira monga kukhwinyata m'mphuno, kuyetsemula, zilonda zapakhosi, chifuwa;

▪ zidzolo;

▪ Kupweteka kwa minofu, mafupa, ndi mafupa;

▪ Kuyezetsa magazi molakwika;

▪ Kutopa;

▪ Kuchepetsa thupi; kapena

▪ Mtundu wa tsitsi umayamba kuwalira.

Izi siziri mndandanda wathunthu wa zotsatirapo ndipo ena akhoza kuchitika. Dandauzani dokotala wanu kuti akuthandizeni zachipatala zokhudzana ndi zotsatira. Mutha kuyankha FDA ku 1-800-FDA-1088.

 

Kukula Kwaposachedwa Kwa Kabozantinib 

Cabozantinib adapatsidwa mankhwala amasiye ndi US Food and Drug Administration (FDA) mu Novembala 2010 komanso mu February 2017.

Exelixis adalemba ntchito yatsopano ku FDA mu theka loyamba la 2012 ndipo pa Novembala 29, 2012 cabozantinib mu kapule kapangidwe kake idapatsidwa chilolezo chotsatsa ndi US FDA yotchedwa Cometriq pochiza odwala khansa ya chithokomiro cha medullary. ovomerezeka ku European Union pachifukwa chomwecho mu 2014.

Mu Marichi 2016 Exelixis idapatsa chilolezo ku Ipsen ufulu wapadziko lonse lapansi (kunja kwa US, Canada, ndi Japan) kuti agulitse cabozantinib.

Zotsatira za kuyesa kwa Exelixis Phase III kuyesa mankhwalawo mu impso khansa lofalitsidwa mu NEJM mu 2015. Mu Epulo 2016 a FDA adapereka chilolezo chotsatsa mapiritsi ngati njira yachiwiri yothandizira impso khansa ndipo zomwezo zidavomerezedwa ku European Union mu Seputembala chaka chimenecho.

Mu Disembala 2017, a FDA adavomereza cabozantinib (Cabometyx, Exelixis, Inc.) yothandizira anthu omwe ali ndi renal cell carcinoma (RCC). Chivomerezocho chinachokera ku data kuchokera ku CABOSUN (NCT01835158), kafukufuku wosavuta, wotseguka gawo lachiwiri II wophunzitsira mwa omwe anali nawo mu 157 omwe ali ndi RCC yapakati komanso yopanda chiyembekezo.

Mu January 2019, a FDA idavomereza cabozantinib (Cabometyx, Exelixis, Inc.) ya anthu omwe ali ndi hepatocellular carcinoma (HCC) omwe amathandizidwapo ndi sorafenib. Chivomerezocho chimachokera ku CELESTIAL (NCT01908426), chosasinthika (2: 1), khungu lakhungu, lolamulidwa ndi placebo, loyeserera kwa onse omwe ali ndi HCC omwe adalandira sorafenib kale ndipo anali ndi vuto la chiwindi cha Child Pugh Class A.

Cabozantinib ikufufuzidwa kuti igwire bwino ngati chithandizo cha neurofibromatosis mtundu wa 1.

Food and Drug Administration (FDA) posachedwa idavomereza cabozantinib yothandizira hepatocellular carcinoma mwa odwala omwe kale adalandira sorafenib.

Cabozantinib ndi mulomo wa tyrosine kinases inhibitor wa MET, VEGFR, ndi AXL.

A FDA adavomereza kabozantinib koyamba kuti akalandire mankhwala khansa ya chithokomiro. Pambuyo pake, a FDA adavomereza kuti agwiritse ntchito renal cell carcinoma.

 

Nkhani Za Kuchiza kwa Cabozantinib Nkhani Zabwino 

Nkhani 1: Cabozantinib Chitani Chithandizo Choyamba Chotsatira cha Renal Cell Carcinoma

Pa Disembala 19, 2017, US Food and Drug Administration (FDA) idapereka chilolezo kwa cabozantinib (Cabometyx) yothandizira odwala omwe ali ndi renal cell carcinoma (RCC).

A FDA adavomereza kale cabozantinib ku 2016 kuti azithandizira odwala omwe ali ndi RCC omwe adalandirapo antiangiogenic. Kuvomereza kwamasiku ano kumapereka chithandizo munthawi yoyamba.Kabozantinib

Kuvomerezedwa kumeneku kunatengera chidziwitso cha kuyesedwa kwa CABOSUN, kafukufuku wosavuta, wotseguka gawo lachiwiri II mwa odwala 157 omwe ali ndi RCC wapakatikati- komanso woopsa omwe sanalandire chithandizo. Odwala amalandira cabozantinib (n = 79) 60 mg pakamwa tsiku lililonse kapena sunitinib (Sutent) (n = 78) 50 mg pakamwa tsiku lililonse (masabata 4 akamalandira chithandizo ndikutsatiridwa ndi milungu iwiri) mpaka matenda atha kukula kapena poyizoni wosavomerezeka. Kuyerekeza kupulumuka kwapakatikati kwapakatikati (monga kuyesedwa ndi komiti yoyeserera yoyeserera ya radiology) kwa odwala omwe amatenga cabozantinib anali miyezi 2 (8.6% interval [CI] = 95-6.8) poyerekeza ndi miyezi 14.0 (5.3% CI = 95-3.0) ya odwala omwe amatenga sunitinib (chiopsezo cha chiopsezo = 8.2; 0.48% CI = 95-0.31; P = .0.74).

Zomwe zimadziwika kwambiri (≥ 25%) zomwe zimachitika mu cabozantinib pulogalamu yamatenda ndi kutsekula m'mimba, kutopa, nseru, kuchepa kwa njala, matenda oopsa, erythrodysesthesia, kutsitsa, kusanza, dysgeusia, ndi stomatitis.

Matenda omwe amapezeka pafupipafupi 3-4 (≥ 5%) mwa odwala omwe ali ndi cabozantinib pa CABOSUN anali matenda oopsa, kutsegula m'mimba, hyponatremia, hypophosphatemia, erythrodysesthesia, kutopa, kuwonjezeka kwa ALT, kuchepa kwa njala, stomatitis, kupweteka, hypotension, ndi kulunzanitsa. Mlingo woyenera wa cabozantinib ndi 60 mg pakamwa, kamodzi patsiku.

Cabozantinib imavomerezedwanso ngati chithandizo cha khansa ya chithokomiro ya medullary ndipo imagulitsidwa pansi pa dzina la malonda Cometriq. Cometriq ndi Cabometyx ali ndi mawonekedwe osiyanasiyana ndipo sasinthana.

 

Nkhani 2: Cabozantinib Chitani Khansa Yam'mimba Yam'mero ​​Yam'mimba

A FDA adavomereza cabozantinib (Cometriq) kuti athetse khansa ya chithokomiro ya metastatic medullary medullary (MTC) mu Novembala 2012. Zinatengera zotsatira za mayesero apadziko lonse lapansi, multicenter, randomized, blind-blind, ophatikizika kuphatikiza maphunziro a 330. Ophunzira adayenera kuwonetsa matenda omwe akupita patatha miyezi 14 asanaphunzire, zomwe zidatsimikiziridwa kudzera mu komiti yodziyimira payokha ya radiology kapena dokotala wothandizira.

Odwala adasinthidwa mwachisawawa kuti alandire cabozantinib 140 mg kapena placebo pakamwa kamodzi tsiku lililonse mpaka matenda opitilira patsogolo kapena poyizoni wosapiririka. Randomization idasinthidwa malinga ndi zaka <65 zaka vs> 65 zaka ndikugwiritsanso ntchito tyrosine kinase inhibitor.Kabozantinib

Mapeto oyambira anali kupulumuka kopanda kupita patsogolo (PFS), kuyankha kwakanthawi (OR), komanso nthawi yoyankha pogwiritsa ntchito njira zosinthidwa za RECIST. Odwala omwe anali mgulu la cabozantinib anali atakhala ndi PFS yayitali poyerekeza ndi omwe amalandira placebo (P <.0001). Makamaka, ma PFS apakati pamikono ya cabozantinib anali miyezi 11.2 ndipo apakatikati a PFS m'manja mwa placebo anali miyezi 4.0.

Odwala okha omwe amatenga cabozantinib ndi omwe amayankhidwa pang'ono (27% vs 0; P <.0001). Kuphatikiza apo, nthawi yapakatikati ya OR inali miyezi 14.7 kwa omwe amathandizidwa ndi mankhwalawa. Palibe kusiyana kwakukulu pakupulumuka konse komwe kunawonedwa pakati pa mikono.

Pakuwunika meta- ndi chuma cha 2019 kuwunika momwe cabozantinib ndi vandetanib amagwiritsira ntchito odwala ku England National Health Service, Tappenden et al. Kutsiriza.

"Mayesero omwe adadziwika akusonyeza kuti cabozantinib ndi vandetanib zimawongolera PFS kuposa malowa; komabe, zopindulitsa zazikulu za OS sizinawonetsedwe. Kafukufuku wachuma akuwonetsa kuti mwa anthu omwe ali ndi zilembo za EU, ma ICERs [ndalama zowonjezerapo zogulira mtengo] za cabozantinib ndi vandetanib ali> £ 138,000 pa QALY (chaka chosintha chamakhalidwe) chomwe chapezeka. M'mayiko oletsedwa a EU (European Union), ICER ya vandetanib ikuyembekezeka kukhala> £ 66,000 pa QALY yomwe yapindula. ”

 

Nkhani 3: Cabozantinib Chitani Hepatocellular Carcinoma

Mu Januwale 2019, a FDA adavomereza mapiritsi a cabozantinib a odwala omwe ali ndi hepatocellular carcinoma (HCC) idathandizidwa kale ndi sorafenib. Chivomerezocho chinachokera pa zotsatira za kuyesedwa kwa CELESTIAL.

Mu randomised (2: 1), blind-blind, control-placebo, multicenter test, odwala adasinthidwa kukhala cabozantinib 60 mg pakamwa kamodzi tsiku lililonse (n = 470) kapena placebo (n = 237) mpaka nthawi yakukula kwa matenda kapena yosavomerezeka kawopsedwe.Kabozantinib

Pomaliza pake panali OS. PFS ndi ORR, zowunikidwa ndi ofufuza pogwiritsa ntchito RECIST 1.1, adayesedwa. Kugwiritsa ntchito kwa Cabozantinib kumalumikizidwa ndi OS yapakatikati ya miyezi 10.2 (95% CI: 9.1-12.0) vs 8 miyezi (95% CI: 6.8-9.4) kwa omwe alandire placebo (HR 0.76; 95% CI: 0.63, 0.92; P = .0049). Median PFS inali miyezi 5.2 (4.0-5.5) m'manja mwa cabozantinib poyerekeza ndi miyezi 1.9 (1.9-1.9) m'manja mwa placebo (HR 0.44; 95% CI, 0.36, 0.52; P <.001). ORR inali 4% (95% CI, 2.3, 6.0) mwa iwo omwe amatenga cabozantinib vs 0.4% (95% CI, 0.0, 2.3) mwa iwo omwe amatenga placebo.

Zochitika zoyipa za Gulu 3 kapena 4 zinali zazikulu mwa odwala omwe amatenga cabozantinib (68%) kuposa omwe amatenga placebo (36%).

Olemba mlandu wa CELESTIAL anamaliza ndi izi: "Pakati pa odwala omwe anali ndi kachilombo koyambitsa matenda a hepatocellular carcinoma, chithandizo cha cabozantinib chidapangitsa kuti pakhale moyo wawutali komanso wopitilira patsogolo kuposa placebo. Kuchuluka kwa zochitika zoyipa kwambiri pagulu la cabozantinib kunali pafupifupi kawiri zomwe zidawonedwa pagulu la placebo. ”

 

Chidule

Cabozantinib ndi tyrosine kinase inhibitor yomwe imagwiritsidwa ntchito pochizira matenda a renal cell carcinoma, hepatocellular carcinoma, komanso khansa ya chithokomiro ya medullary. Cabozantinib idavomerezedwa koyamba mu 2012 ndipo siyodziwika bwino ya tyrosine kinase inhibitor. Poyamba idavomerezedwa ku US pansi pa dzina la Cometriq, lomwe limawonetsedwa ngati chithandizo cha khansa yamatenda a metastatic medullary.Zamgululi) adavomerezedwa kuchiza matenda a renal cell carcinoma, ndipo mapangidwe omwewo adalandiranso chilolezo ku US ndi Canada ku 2019 kuchiza hepatocellular carcinoma mwa odwala omwe adathandizidwa kale.

AASraw ndiye katswiri wopanga Cabozantinib.

Chonde dinani apa kuti mumve zambiri: Ochezera ife

 

Reference

[1] Choueiri TK, Escudier B, Powles T, ndi al. Cabozantinib motsutsana ndi everolimus mu advanced renal cell carcinoma (METEOR): zotsatira zomaliza kuchokera pamayeso osasinthika, otseguka, gawo la 3. Lancet Oncol. 2016; 17: 917-27.

[2] Tappenden P, Carroll C, Hamilton J, ndi al. Cabozantinib ndi vandetanib chifukwa cha khansa ya chithokomiro yosasunthika kwanuko kapena metastatic medullary: kuwunika mwatsatanetsatane komanso mtundu wazachuma. Kuunika kwa Health Technol. 2019; 23: 1-144.

[3] George DJ, Hessel C, Halabi S, ndi al. Cabozantinib motsutsana ndi sunitinib kwa odwala omwe sanalandire chithandizo omwe ali ndi vuto la renal cell carcinoma la pakatikati kapena pangozi yovuta: kuwunika kwa kagulu ka mayeso a Alliance A031203 CABOSUN. Katswiri wazachipatala. 2019; 24: 1-5.

[4] Kurzrock R, Sherman SI, Ball 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 (Adasankhidwa) , Salgia R: Ntchito ya XL184 (Cabozantinib), m'kamwa tyrosine kinase inhibitor, mwa odwala khansa ya chithokomiro ya medullary. J Clin Oncol. (Adasankhidwa) 2011 Jul 1; 29 (19): 2660-6. onetsani: 10.1200 / JCO.2010.32.4145. Epub 2011 Meyi 23.

[5] Abou-Alfa GK, Meyer T, Cheng AL, ndi al. Cabozantinib mwa odwala omwe ali ndi khansa ya hepatocellular carcinoma. N Engl J Med. 2018; 379: 54-63.

[6] Ulamuliro wa Zakudya ndi Mankhwala ku US. FDA imavomereza cabozantinib ya hepatocellular carcinoma. Ipezeka pa: https://www.fda.gov/drugs/fda-approves-cabozantinib-hepatocellular-carcinoma Ipezeka pa Ogasiti 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, You A, Laird AD, Engst S, Lee L, Lesch J, Chou YC , Joly AH: Cabozantinib (XL184), buku la MET ndi VEGFR2 inhibitor, nthawi yomweyo limafinya metastasis, angiogenesis, ndi kukula kwa chotupa. Khansa ya Mol. 2011 Dis; 10 (12): 2298-308. onetsani: 10.1158 / 1535-7163.MCT-11-0264. Epub 2011 Sep 16.

[8] "Mankhwala a khansa ya chithokomiro cabozantinib imachulukitsa PFS". Zosungidwa kuchokera pachiyambi pa 2012-04-02. Kubwezeretsedwa 24 October 2011.

[9] "Cabozantinib Orphan Mankhwala Osokoneza bongo ndi Kuvomerezeka". US Food and Drug Administration (FDA). 29 Novembala 2010. Chotsatira 11 Novembala 2020.

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