FDA Yavomereza Regorafenib Kuchiza Khansa Yoyenera - GIST - HCC
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Zoyipa

 

  1. Regorafenib ndi chiyani?
  2. Chifukwa chiyani Regorafenib Yavomerezedwa ndi FDA?
  3. Kodi Regorafenib imagwira ntchito bwanji?
  4. Kodi Regorafenib Main Ntchito Yotani?
  5. Ndi ma Phindu ati a Regorafenib omwe awonetsedwa mu Study?
  6. Ndi zoopsa / zoyipa ziti zomwe Regorafenib May Atha Kubweretsa?
  7. Kodi ndimasunga bwanji kapena kutaya Regorafenib?
  8. Mayendedwe amtsogolo a Regorafenib
  9. Kutsiliza

 

Kodi Zoyipa?

Regorafenib (CAS: 755037-03-7), yogulitsidwa pansi pa dzina la Stivarga pakati pa ena, ndi pakamwa ma kinase inhibitor ambiri yopangidwa ndi Bayer yomwe imayang'ana angiogenic, stromal and oncogenic receptor tyrosine kinase (RTK). Regorafenib ikuwonetsa zinthu zotsutsana ndi angiogenic chifukwa cha VEGFR2-TIE2 tyrosine kinase inhibition. Kuyambira 2009 idaphunziridwa ngati njira yothetsera matenda m'mitundu ingapo yam'mimba. Pofika mu 2015 idavomereza ku US ma khansa apamwamba.

 

Chifukwa chiyani Regorafenib Zavomerezedwa ndi FDA

The European Medicines Agency adaganiza kuti zabwino za Regorafenib ndizochulukirapo kuposa zoopsa zake ndipo adalimbikitsa kuti zivomerezedwe kuti zigwiritsidwe ntchito ku EU. Komitiyi inanena kuti mu khansa yoyipa phindu lokhalitsa kupulumuka kwa odwala linali lochepa, koma linawona kuti likuposa zoopsa za odwala omwe alibe njira zina zotsalira. Komabe, potengera zotsatirapo zake, CHMP idawona kuti ndikofunikira kupeza njira zodziwira magulu ang'onoang'ono a odwala omwe atha kuyankha ku Stivarga.

Ponena za GIST ndi HCC, Komitiyi idawona kuti malingaliro siabwino kwa odwala omwe matenda awo amakula ngakhale adalandira chithandizo cham'mbuyomu. Stivarga adawonetsedwa kuti achedwetsa kukulira kwa matendawa mwa odwalawa. Kwa odwala omwe ali ndi HCC, izi zidabweretsa kusintha kwakanthawi komwe odwala amakhala. Zotsatira zoyipa za Stivarga ndizotheka.

 

Kodi Amachita Bwanji? Zoyipa Ntchito? 

Regorafenib ndi kamolekyulu kakang'ono kolepheretsa ma membrane angapo okhala ndi ma cell ophatikizika omwe amagwira ntchito zama cell komanso machitidwe am'magazi monga oncogenesis, chotupa angiogenesis, komanso kukonza kwa chotupacho microenvelo. Mu vitro biochemical kapena ma cell test, regorafenib kapena ma metabolites akuluakulu a M-2 ndi M-5 amaletsa zochitika za RET, VEGFR1, VEGFR2, VEGFR3, KIT, PDGFR-alpha, PDGFR-beta, FGFR1, FGFR2, TIE2, DDR2, TrkA, Eph2A, RAF-1, BRAF, BRAFV600E, SAPK2, PTK5, ndi Abl m'magawo a regorafenib omwe akwaniritsidwa kuchipatala. M'magulu a vivo, regorafenib adawonetsa anti-angiogenic mu chotupa cha makoswe, komanso kuletsa kukula kwa chotupa komanso ntchito zotsutsana ndi metastatic m'mitundu ingapo yama xenograft kuphatikiza ena a colorectal carcinoma.

AASraw ndiye katswiri wopanga Regorafenib.

Chonde dinani apa kuti mumve zambiri: Ochezera ife

 

Kodi Zoyipa Main Ntchito?

Regorafenib ndi mankhwala a khansa omwe amakhala ndi mankhwalawa regorafenib ufa. Amagwiritsidwa ntchito paokha pochiza khansa zotsatirazi:

Cancer Khansa yoyipa (khansa ya m'matumbo ndi m'matumbo) yomwe yafalikira mbali zina za thupi;

Tumor Matumbo otupa m'mimba (GIST, khansa ya m'mimba ndi matumbo) yomwe yafalikira kapena singathe kuchotsedwa;

③ Hepatocellular carcinoma (HCC, khansa ya chiwindi).

Regorafenib imagwiritsidwa ntchito kwa odwala omwe adalandira kale, kapena omwe sangapatsidwe, mankhwala ena omwe alipo. Kwa khansa yoyipa, izi zimaphatikizapo chemotherapy potengera mankhwala omwe amatchedwa fluoropyrimidines ndi chithandizo ndi ena khansa mankhwala omwe amadziwika kuti anti-VEGF komanso anti-EGFR. Odwala omwe ali ndi GIST amayenera kuyesa mankhwala ndi imatinib ndi sunitinib ndipo odwala omwe ali ndi HCC amayenera kuyesa sorafenib asanayambe kulandira chithandizo ndi Regorafenib.

 

Zoyipa

 

Ubwino Wotani wa Zoyipa awonetsedwa mu Studies?

 Khansara yolondola

Pakafukufuku wamkulu wokhudza odwala 760 omwe ali ndi khansa ya m'matumbo yomwe idapitilira pambuyo pa chithandizo chamankhwala, Regorafenib adafaniziridwa ndi placebo (dummy treatment) ndipo njira yayikulu yogwira ntchito inali kupulumuka konse (kutalika kwa nthawi yomwe odwala amakhala). Odwala onse amalandiranso chithandizo chothandizira, kuphatikizapo mankhwala opweteka komanso chithandizo cha matenda. Kafukufukuyu adawonetsa kuti Regorafenib idakulitsa kupulumuka, ndikuchiza odwala omwe amakhala miyezi 6.4 pafupipafupi, poyerekeza ndi miyezi 5 ya omwe apatsidwa malowa.

 

 GULANI(MwaukadauloZida m'mimba Stromal Zotupa)

Pakafukufuku wina wamkulu, Regorafenib adafaniziridwa ndi placebo mwa odwala 199 omwe ali ndi GIST omwe adafalikira kapena osagwira ntchito komanso omwe amathandizidwa moyenera. Chithandizo chothandizira chimaphatikizapo chithandizo chamankhwala monga kupweteketsa ululu, maantibayotiki, komanso kuthiridwa magazi zomwe zimamuthandiza koma osamuchiritsa khansa. Kafukufukuyu adawonetsa kuti Regorafenib wokhala ndi chisamaliro chothandizira anali othandiza poonjezera kutalika kwa nthawi yomwe odwala amakhala popanda matenda awo kukulira. Odwala omwe amathandizidwa ndi Regorafenib amakhala pafupifupi miyezi 4.8 popanda matenda awo kukulira poyerekeza ndi miyezi 0.9 ya odwala omwe amalandira placebo ndi chisamaliro chothandizira.

 

 HCC(MwaukadauloZida Hepatocellular Carcinoma)

Pakafukufuku wamkulu wokhudza odwala 573 omwe ali ndi HCC omwe anali atakulirakulira atalandira chithandizo ndi sorafenib, Zoyipa poyerekeza ndi placebo ndipo njira yayikulu yogwira ntchito inali kupulumuka konse. Odwala onse nawonso amalandila chithandizo. Kafukufukuyu adawonetsa kuti Stivarga idakulitsa kutalika kwa nthawi yomwe odwala amakhala ndi moyo wonse, pomwe odwala amathandizidwa ndi Regorafenib amakhala miyezi 10.6 pafupipafupi, poyerekeza ndi miyezi 7.8 ya omwe apatsidwa malowa.

 

Zomwe Ziwopsezo / zoyipa zimachita Zoyipa Mungabweretse?

Ikachilombo. Regorafenib itha kubweretsa chiopsezo chachikulu chotenga matenda makamaka kwamikodzo, mphuno, pakhosi ndi m'mapapo. Regorafenib itha kubweretsa chiopsezo chachikulu chotenga mafangasi am'mimba, khungu kapena thupi. Uzani wothandizira zaumoyo wanu nthawi yomweyo ngati mukudwala malungo, chifuwa chachikulu kapena kuwonjezeka kwa ntchofu (sputum), zilonda zapakhosi, kupuma movutikira, kutentha kapena kupweteka mukakodza, kutuluka kwachilendo kwachilendo kapena kupsa mtima, kufiira, kutupa kapena kupweteka m'mbali iliyonse ya thupi

Skutuluka magazi kwambiri. Regorafenib imatha kuyambitsa magazi, omwe amatha kukhala owopsa ndipo nthawi zina amapha. Uzani wothandizira zaumoyo wanu ngati muli ndi zizindikiro zakutaya magazi mukamamwa Regorafenib, kuphatikiza: kusanza magazi kapena ngati masanzi anu akuwoneka ngati malo a khofi, mkodzo wapinki kapena wofiirira, ofiira kapena akuda (akuwoneka ngati phula), akutsokomola magazi kapena magazi, Kutaya magazi msambo kolemetsa kuposa mwakale, kutuluka mwazi kwachilendo, mphuno kutuluka magazi komwe kumachitika nthawi zambiri, kuphwanya, ndi mutu wopepuka.

A gwetsani m'mimba mwanu kapena m'matumbo (zotsekemera m'matumbo). Regorafenib itha kubweretsa misozi m'mimba mwanu kapena m'matumbo omwe amatha kukhala owopsa ndipo nthawi zina amapha. Lumikizanani ndi omwe amakuthandizani azaumoyo mukazindikira zowawa zazikulu kapena zotupa m'mimba mwanu (pamimba), malungo, kuzizira, nseru, kusanza, kapena kutaya madzi m'thupi.

A Vuto lakhungu lotchedwa khungu loyendetsa dzanja phazi komanso zotupa zazikulu pakhungu. Khungu lakumanja kwa phazi ndilofala ndipo nthawi zina limakhala lovuta. Uzani wothandizira zaumoyo wanu nthawi yomweyo mukayamba kufiira, kupweteka, matuza, magazi, kapena kutupa m'manja mwanu, kapena zotupa zamapazi anu, kapena zotupa zazikulu.

Hkuthamanga kwa magazi. Kuthamanga kwa magazi kwanu kuyenera kuyang'aniridwa sabata iliyonse kwa masabata 6 oyambira kuyambira Regorafenib. Kuthamanga kwanu kwa magazi kuyenera kufufuzidwa pafupipafupi ndipo kuthamanga kwa magazi kulikonse kuyenera kuthandizidwa mukalandira Regorafenib. Uzani wothandizira zaumoyo wanu ngati muli ndi mutu wopweteka kwambiri, mutu wopepuka, kapena masomphenya anu.

Damachepetsa kuthamanga kwa magazi kumtima ndi mtima. Pezani thandizo ladzidzidzi ngati mukumva kupweteka pachifuwa, mumakhala ndi mpweya wochepa, mumamva chizungulire, kapena mumamva ngati mukufuna kutuluka.

A chikhalidwe chotchedwa reversible posterior leukoencephalopathy syndrome (RPLS). Itanani nthawi yomweyo omwe amakuthandizani azaumoyo mukadwala mutu, kulanda, kusokonezeka, kusintha masomphenya, kapena kuganiza molakwika

Risk ya mabala akuchiritsa. Mabala sangachiritse bwino panthawi ya chithandizo cha Regorafenib. Uzani wothandizira zaumoyo wanu ngati mukufuna kuchitidwa opaleshoni musanayambe kapena mukamalandira chithandizo ndi Regorafenib.

▪ Muyenera kusiya kumwa Regorafenib pafupifupi milungu iwiri musanachite opareshoni.

▪ Wothandizira zaumoyo wanu akuyenera kukuwuzani nthawi yomwe mungayambenso kumwa Regorafenib mukatha opaleshoni.

Zotsatira zoyipa kwambiri ndi Regorafenib zimaphatikizapo kupweteka kuphatikiza m'mimba-m'mimba (pamimba); kutopa, kufooka, kutopa; kutsegula m'mimba (kuyenda pafupipafupi kapena kutayirira); kuchepa kwa njala; matenda; mawu kusintha kapena hoarseness; kuonjezera mayesero ena a chiwindi; malungo; kutupa, kupweteka, ndi kufiyira kwa m'kamwa mwako, mmero, m'mimba, ndi matumbo (mucositis); ndi kuonda.

AASraw ndiye katswiri wopanga Regorafenib.

Chonde dinani apa kuti mumve zambiri: Ochezera ife

 

Kodi ndimasunga bwanji kapena kutaya Regorafenib?

♦ Sungani mapiritsi mu chidebe choyambirira kutentha. Sungani chipewa mwamphamvu kwambiri. Osatulutsa kacube kapena paketi ya antimoisture.

♦ Tayani gawo lililonse lomwe simunagwiritse ntchito milungu 7 mutatsegula botolo.

♦ Sungani pamalo ouma. Osasunga kubafa.

Sungani mankhwala onse pamalo otetezeka. Sungani mankhwala onse kutali ndi ana ndi ziweto.

Kutaya mankhwala omwe sanagwiritsidwe ntchito kapena atha ntchito. Osamatsuka mchimbudzi kapena kutsanulira ngalande pokhapokha mutauzidwa kutero. Funsani ndi wamankhwala wanu ngati muli ndi mafunso okhudza njira yabwino yotayira mankhwala osokoneza bongo. Pakhoza kukhala mapulogalamu obwezeretsa mankhwala osokoneza bongo mdera lanu.

 

Zoyipa

 

Zotsatira zamtsogolo of Zoyipa

Zaka zisanu atavomerezedwa, regorafenib amakhalabe mankhwala osagwiritsa ntchito kwambiri zamankhwala. Kugwiritsa ntchito kovomerezeka mu khansa yamtundu wamtundu wamtundu, GIST ndi HCC ndi matenda am'mapapo okha. Kuphatikiza ndi mtengo wokwera, pakadali pano phindu lochepera la odwala. Kuphatikiza apo, mayesero osiyanasiyana akuchitidwa kuti afotokozere ngati njira yatsopano yothandizira. Malangizo amtsogolo a mankhwalawa akuphatikizapo kasamalidwe ka osteosarcoma. Kuyesedwa kwaposachedwa kwa placebo, kuwunika kwakhungu kawiri ku France kwawonetsa kuwonjezeka kwa kupulumuka kopanda kupita patsogolo chifukwa cha 3 mwa odwala omwe ali ndi metastatic osteosarcoma omwe alephera chithandizo chilichonse. Mokakamiza, izi zatsopano zikuwonetsa kupindula ndi matenda a metastatic ngati njira yomaliza, chimodzimodzi ndi magwiritsidwe onse ovomerezeka.

Zomwe zaposachedwa zikuwonetsa kuthekera kwa synergic pakati pa regorafenib ndi immune checkpoint inhibitors, monga zawonetsedwa mu kuyesedwa kwa REGONIVO. (38% mu khansa ya m'mimba ndi 44% ya khansa yoyipa) komanso mbiri yoyipa yamaguluwo. Phindu lochititsa chidwi lingakhale chifukwa cha kuchepa kwa macrophages okhudzana ndi chotupa ndi regorafenib, kukulitsa chidwi cha tumour ku nivolumab. Pakadali pano, kuyesa kwa REGONIVO gawo lachiwiri kuli mkati ndipo kungathe kutsimikizira izi. Kuphatikiza apo, gawo lomaliza lachiwiri lakuwonetsetsa kwachipatala lawonetsa kuti regorafenib ndiyabwino kuposa lomustine mu glioblastoma yapamwamba komanso yobwereranso.Muyeso wa REGOMA, ku Italy, wasonyeza kusintha kwakukulu pakukhalanso ndi moyo (chiopsezo cha 36; 0.50% interval confidence 95-0.33; log-rank p = 0.75) poyerekeza ndi mankhwala a lomustine.

Kafukufuku wa REVERSE adachitidwa ndi regorafenib ndi cetuximab pochiza khansa ya m'matumbo. Zotsatira zomwe zidapezeka potsatira kugwiritsidwa ntchito kwa mankhwalawa pochiza khansa iyi zikuwonetsa kuti dongosolo loyenera lingakhale kuyang'anira koyamba kwa regorafenib kutsatiridwa ndi cetuximab, mosiyana ndi njira yomwe imagwiritsidwa ntchito pano. Zotsatirazo zikuwonetsa kupulumuka kwathunthu kwa odwala ndipo phindu limawoneka kuti limayendetsedwa makamaka ndi ntchito yayikulu ya cetuximab kuposa regorafenib ngati chithandizo chachiwiri.

WOKHUDZA mayesero a regorafenib monotherapy mu khansa ya m'mimba idawonetsa kuti mankhwalawa adalekerera bwino komanso kuti palibe kuwonongeka kwaumoyo wa odwala poyerekeza ndi omwe adalandira malowa ndipo sizikuwoneka kuti zikuwononga kwambiri magawo a poizoni. Kafukufuku adanenanso kuti zowawa zoyambira, kulakalaka, kudzimbidwa, komanso kugwira ntchito zolimbitsa thupi zimapezeka kuti ndizofunikira pakulosera zakupulumuka. Komanso, mayeserowa adawonetsa kuti regorafenib anali ndi zochitika zambiri kumapeto komaliza kopanda kupulumuka. Kuyesedwa kwa REDOS kunachitika kuchokera ku 2015-2018 ndipo olemba adawonetsa kuti njira yochulukitsira mlingo wa regorafenib ndi njira yothetsera vuto la regorafenib dosing strategy ya 160 mg / tsiku, makamaka kwa odwala omwe ali ndi khansa ya m'matumbo. Zinapezekanso kuti odwala omwe amathandizidwa ndi kuchuluka kwa mlingo amakhala ndi pafupipafupi chithandizo chamankhwala chotsatira pambuyo pake komanso kupulumuka kwakanthawi kwakanthawi.

Ponena za kulolerana kwa regorafenib mukamagwiritsidwa ntchito kuchiza khansa yoyipa, zochepa zopezeka pakulekerera kwa okalamba, ndipo chigamulochi chiyenera kupangidwa poganizira za phindu locheperako komanso mbiri ya poizoni. Poganizira za mankhwalawa mu chithandizo cha HCC, ntchito zofufuzira zimatsindika kuti pali kulolerana komwe kulipo komanso kuti regorafenib imapereka phindu. Chithandizo cha GIST, olemba angapo akuti regorafenib imaloledwa bwino popanda zoopsa zosayembekezereka.

Kafukufuku wowonjezereka amafunikira kuti adziwe odwala omwe angapindule kwambiri ndi mankhwalawa. Kuyambira mu 2019, mayesero omwe akupitilirabe akuyesa ngati regorafenib itha kusintha zotsatira zake mu minofu yofewa, monga osteogenic sarcoma, liposarcoma, Ewing sarcoma ndi rhabdomyosarcoma.

 

Kutsiliza

Ngakhale zaka 5 zavomerezedwa ndikulonjeza pharmacodynamics, regorafenib yawonetsa zopindulitsa zochepa, koma zowerengera, zopindulitsa pamatenda osiyanasiyana olimba. Zizindikiro zolembedwa zimakhala ndi khansa yoyipa, GIST ndi HCC. Mayeso apamwamba a gawo lachiwiri awonetsa kusintha kwakukulu pakupulumuka kwa khansa ya m'mimba, glioblastoma ndi osteosarcoma, zomwe zitha kuwonetsa kuphatikizidwa mtsogolo m'mawu olembedwa.

Mankhwala ophatikizana omwe ali ndi ma chitetezo a chitetezo cha mthupi awonetsedwa kuti ndi othandiza pamayeso a gawo I, ndipo mayeso achigawo chachiwiri akuchitidwa. Pakadali pano, regorafenib ikufufuzidwanso ma khansa ena. Zotsatira zoyipa zambiri zitha kugwiritsidwa ntchito ngati zolembera pazotsatira zabwino ndi chithandizo. Mwa zina, matenda am'manja ndi hypothyroidism ndizomwe zimakhudzana kwambiri ndi kupulumuka kwamoyo. Mwachidule, kafukufuku wasonyeza kuti regorafenib itha kusintha kwambiri kupulumuka ndi kulolerana kovomerezeka m'matumbo olimba osiyanasiyana.

AASraw ndiye katswiri wopanga Regorafenib.

Chonde dinani apa kuti mumve zambiri: Ochezera ife

 

Reference

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[6] Eriksson A, Cao R, Roy J, ndi al. Mapuloteni ang'onoang'ono omanga GTP Rac ndiwofunikira pakuyimira pakati pakumapeto kwamitsempha yam'mimba yopangitsa kuti pakhale endothelial fenestrations komanso kuperewera kwamitsempha. Kuzungulira. 2003; 107: 1532-8.

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[9] Bruix J, Qin S, Merle P, ndi al. Regorafenib kwa odwala hepatocellular carcinoma omwe amapita patsogolo pa mankhwala a sorafenib (RESORCE): kuyeserera kosawoneka bwino, kwakhungu kawiri, kolamulidwa ndi placebo, gawo la 3. Lancet. 2017; 389: 56-66.

[10] Martin AJ, Gibbs E, Sjoquist K, ndi al. Moyo wathanzi wokhudzana ndi thanzi la regorafenib mu refractory advanced gastric adenocarcinoma. Khansa ya m'mimba. 2018; 21: 473-80.

[11] Heo YA, Syed YY. Regorafenib: kuwunika kwa hepatocellular carcinoma. Mankhwala osokoneza bongo. 2018; 78: 951-8.

[12] Yin X, Yin Y, Shen C, Chen H, Wang J, Cai Z, et al. Zowonjezera Zowopsa zomwe zimayambitsidwa ndi regorafenib pochiza zotupa zolimba: meta-kusanthula mayesero olamulidwa mosasintha. Zolinga za Onco Ther. 2018; 11: 6405-14.

[13] Lombardi G, De Salvo GL, Brandes AA, ndi al. Regorafenib poyerekeza ndi lomustine mwa odwala omwe abwereranso ndi glioblastoma (REGOMA): multicentre, open-label, randomized, controlled, phase 2 trial. Lancet Oncol. 2019; 20: 110-9.

[14] Bekaii-Saab T. Kuyang'anitsitsa regorafenib. Kliniki Adv Hematol Oncol. 2018; 16: 667-9.

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