I-FDA evunyelwe iRegorafenib Yelapha Umdlavuza Ongaqondile - GIST 丨 HCC
I-AASraw ikhiqiza izimpushana ze-NMN ne-NRC ngobuningi!

Regorafenib

 

  1. Yini iRegorafenib?
  2. Kungani iRegorafenib ivunywa yi-FDA?
  3. Isebenza kanjani iRegorafenib?
  4. Ngabe iRegorafenib Main Isetshenziselwani?
  5. Yiziphi Izinzuzo zeRegorafenib ezikhonjisiwe kwizifundo?
  6. Yiziphi Izingozi / Imiphumela emibi engalethwa yiRegorafenib May?
  7. Ngigcina kanjani futhi / noma ngilahle iRegorafenib?
  8. Izinkomba zesikhathi esizayo zeRegorafenib
  9. Isiphetho

 

Kuyini Regorafenib?

I-Regorafenib (i-CAS: 755037-03-7), edayiswa ngaphansi kwegama lomkhiqizo i-Stivarga phakathi kwabanye, ngomlomo ama-multi-kinase inhibitor ithuthukiswe yiBayer ehlose i-angiogenic, stromal ne-oncogenic receptor tyrosine kinase (RTK). I-Regorafenib ikhombisa imisebenzi elwa ne-angiogenic ngenxa yokuvinjelwa kwayo okubili okubhekiswe ku-VEGFR2-TIE2 tyrosine kinase. Kusukela ngo-2009 yafundwa njengenketho yokwelashwa engaba khona ezinhlotsheni eziningi zezimila, kwathi ngonyaka wezi-2015 yaba nokugunyazwa okubili kwase-US komdlavuza osezingeni eliphezulu.

 

Kungani iRegorafenib Kuvunyelwe ngu-FDA

The I-European Medicines Agency ithathe isinqumo sokuthi izinzuzo zikaRegorafenib zinkulu kunezingcuphe zayo futhi yancoma ukuthi ivunyelwe ukusetshenziswa e-EU. IKomidi liqaphele ukuthi kumdlavuza onamabala izinzuzo maqondana nokwelula ukusinda kweziguli bezincane, kepha libheke ukuthi zidlula ubungozi ezigulini ezingekho ezinye izindlela zokwelashwa ezisele. Kodwa-ke, uma unikezwe imiphumela engemihle, i-CHMP ikubone kubalulekile ukuthola izindlela zokuhlonza noma yimaphi amaqembu amancane eziguli asethubeni lokuphendula iStivarga.

Mayelana ne-GIST ne-HCC, iKomidi liqaphele ukuthi umbono awumuhle ezigulini ezinezifo eziya ziba zimbi yize belashwa phambilini. UStivarga ubekhonjiswe ukuthi wephuza ukwanda kwesifo kulezi ziguli. Ezigulini ezine-HCC, lokhu kuholele ekuthuthukisweni kobude besikhathi iziguli eziphila ngaso. Imiphumela emibi yeStivarga iyalawuleka.

 

Kanjani Regorafenib Usebenza? 

I-Regorafenib iyi-molecule inhibitor encane yama-kinase amaningi aboshwe ngamangqamuzana nama-intracellular kinases abandakanyeka emisebenzini ejwayelekile yeselula nasezinqubeni ze-pathologic ezifana ne-oncogenesis, i-tumor angiogenesis, kanye nokugcinwa kwe-tumor microenvelo. Kuzilingo ze-in vitro biochemical noma amaselula, i-regorafenib noma i-metabolites yayo esebenzayo yabantu i-M-2 ne-M-5 ivimbele umsebenzi we-RET, VEGFR1, VEGFR2, VEGFR3, KIT, PDGFR-alpha, PDGFR-beta, FGFR1, FGFR2, TIE2, I-DDR2, i-TrkA, i-Eph2A, i-RAF-1, i-BRAF, i-BRAFV600E, i-SAPK2, i-PTK5, ne-Abl ekugxileni kwe-regorafenib okutholwe emtholampilo. Kumamodeli we-vivo, i-regorafenib ikhombise umsebenzi olwa ne-angiogenic kwimodeli yesigaxa segundane, kanye nokuvinjelwa kokukhula kwesimila kanye nomsebenzi olwa nokuqina komzimba kumamodeli amaningana egundane le-xenograft kufaka phakathi amanye e-colorectal carcinoma yabantu.

I-AASraw ingumkhiqizi oqeqeshiwe weRegorafenib.

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Kuyini Regorafenib Okuyinhloko Kusetshenziselwe?

I-Regorafenib ngumuthi womdlavuza oqukethe into esebenzayo regorafenib powder. Isetshenziselwa yona ukwelapha le mdlavuza elandelayo:

Cancer Umdlavuza ohlukanisa imibala (umdlavuza wamathumbu kanye nowe-rectum) osabalele kwezinye izitho zomzimba;

Tumor Isimila esiswini samathumbu (i-GIST, umdlavuza wesisu namathumbu) osakazekile noma ongeke ususwe ngokuhlinzwa;

③ I-Hepatocellular carcinoma (HCC, umdlavuza wesibindi).

I-Regorafenib isetshenziswa ezigulini esezelashwa, noma ezingeke zinikezwe ezinye izindlela zokwelashwa. Ngomdlavuza we-colorectal, lokhu kufaka i-chemotherapy esuselwa emithini ebizwa nge-fluoropyrimidines kanye nokwelashwa kweminye umdlavuza imithi eyaziwa njenge-anti-VEGF kanye nemithi yokwelapha ye-anti-EGFR. Iziguli ezine-GIST bekufanele zizame ukwelashwa nge-imatinib ne-sunitinib kanti iziguli ezine-HCC bekufanele zizame i-sorafenib ngaphambi kokuqala ukwelashwa ngeRegorafenib.

 

Regorafenib

 

Yiziphi izinzuzo ze Regorafenib kukhonjisiwe kwizifundo?

 umdlavuza Colorectal

Ocwaningweni olukhulu olubandakanya iziguli ezingama-760 ezinomdlavuza we-metastatic colorectal obusuthuthuke ngemuva kokwelashwa okujwayelekile, iRegorafenib yaqhathaniswa ne-placebo (i-dummy treatment) futhi isilinganiso esikhulu sokusebenza kwaba ukusinda okuphelele (ubude besikhathi iziguli ezazihlala ngaso). Zonke iziguli zithole ukunakekelwa okwesekayo, kubandakanya nemithi yezinhlungu nokwelashwa kwezifo. Ucwaningo lukhombisile ukuthi iRegorafenib ithuthukise ukusinda, ngeziguli eziphathwayo eziphila izinyanga eziyi-6.4 ngokwesilinganiso, uma kuqhathaniswa nezinyanga ezi-5 zalabo abanikezwe i-placebo.

 

 HLALANI(Izidumbu Ezithuthukile Zamathumbu Esisu)

Kokunye ukuhlola okuyinhloko, iRegorafenib yaqhathaniswa ne-placebo ezigulini ezingama-199 ezine-GIST ezazisabalele noma zazingasebenzi futhi zanikezwa nokunakekelwa okungcono kakhulu kokusekelwa. Ukunakekelwa okusekelayo kufaka phakathi ukwelashwa okunjengokudambisa izinhlungu, ama-antibiotic, kanye nokumpontshelwa igazi okusiza isiguli kepha ngaphandle kokwelashwa umdlavuza. Ucwaningo lukhombisile ukuthi iRegorafenib enakekelwa ngokusekelwa ibisebenza ngempumelelo ekwandiseni ubude besikhathi iziguli eziphila ngaphandle kwesifo sazo ukuba sibi kakhulu. Iziguli ezelashwa ngeRegorafenib ziphila ngokwesilinganiso izinyanga ezingama-4.8 ngaphandle kokugula kwazo ziba zimbi kakhulu uma kuqhathaniswa nezinyanga eziyi-0.9 zeziguli ezithatha i-placebo nokunakekelwa okusekelayo.

 

 HCC(I-Advanced Hepatocellular Carcinoma)

Ocwaningweni olukhulu olubandakanya iziguli ezingama-573 ezine-HCC ezazibe zimbi kakhulu ngemuva kokwelashwa nge-sorafenib, Regorafenib yaqhathaniswa ne-placebo futhi isilinganiso esikhulu sokusebenza kwaba ukusinda jikelele. Zonke iziguli zithole ukunakekelwa okusekelayo. Ucwaningo lukhombisile ukuthi iStivarga inyuse ubude besikhathi iziguli eziphila ngaso sonke, neziguli ezelashwa ngeRegorafenib ziphila izinyanga eziyi-10.6 ngokwesilinganiso, uma kuqhathaniswa nezinyanga eziyi-7.8 kulabo abanikezwe i-placebo.

 

Yenzani ubungozi / imiphumela emibi Regorafenib Ungaletha?

Iukubuthwa. I-Regorafenib ingaholela engcupheni ephezulu yokutheleleka ikakhulukazi yomgudu womchamo, impumulo, umphimbo namaphaphu. I-Regorafenib ingaholela engcupheni ephezulu yokutheleleka kwefungal yolwelwesi lwamafinyila, isikhumba noma umzimba. Tshela umhlinzeki wakho wezempilo khona manjalo uma uthola umkhuhlane, ukukhwehlela okukhulu noma ngaphandle kokwanda kokukhiqizwa kwe-mucus (isikhwehlela), umphimbo obuhlungu kakhulu, ukuphefumula okuncane, ukushisa noma ubuhlungu lapho uchama, ukuphuma okungavamile kwesitho sangasese sowesifazane noma ukucasuka, ubomvu, ukuvuvukala noma ubuhlungu kunoma iyiphi ingxenye yomzimba

Sukuphuma kwegazi okukhulu. I-Regorafenib ingadala ukopha, okungaba kubi kakhulu futhi kwesinye isikhathi kuholele ekufeni. Tshela umhlinzeki wakho wezokunakekelwa kwezempilo uma unezimpawu zokopha ngenkathi uthatha iRegorafenib, kufaka phakathi: ukuhlanza igazi noma uma ukuhlanza kwakho kubukeka njengezindawo zekhofi, umchamo opinki noma onsundu, obomvu noma omnyama (kubukeka njengetiyela), ukhwehlela igazi noma amahlule egazi, ukopha kokuya esikhathini okunzima kakhulu kunokujwayelekile, ukopha okungavamile kwesitho sangasese sowesifazane, ukuphuma kwegazi emakhaleni okwenzeka kaningi, ukulimaza, kanye nekhanda elikhanyayo.

A dabula esiswini sakho noma odongeni lwamathumbu (ukugcotshwa kwamathumbu). I-Regorafenib ingadala izinyembezi esiswini sakho noma odongeni lwamathumbu okungaba kubi kakhulu futhi kwesinye isikhathi kuholele ekufeni. Xhumana nomhlinzeki wakho wezokunakekelwa kwempilo ngokushesha uma ubona izinhlungu ezinzima noma ukuvuvukala esiswini sakho (isisu), imfiva, ukugodola, isicanucanu, ukuhlanza noma ukoma.

A inkinga yesikhumba ebizwa ngokuthi yi-hand-foot skin reaction kanye nokuqubuka okukhulu kwesikhumba. Ukuphendula kwesikhumba sezinyawo zezandla kuvamile futhi kwesinye isikhathi kungaba nzima. Tshela umhlinzeki wakho wezempilo ngokushesha uma uthola ubomvu, izinhlungu, amabhamuza, ukopha, noma ukuvuvukala ezintendeni zezandla zakho nasematheni ezinyawo zakho, noma ukuqubuka okukhulu.

Humfutho wegazi igh. Umfutho wegazi lakho kufanele uhlolwe masonto onke emavikini ayisithupha okuqala okuqala iRegorafenib. Umfutho wegazi lakho kufanele uhlolwe njalo futhi noma imuphi umfutho wegazi ophakeme kufanele welashwe ngenkathi uthola iRegorafenib. Tshela umhlinzeki wakho wezokunakekelwa kwempilo uma unekhanda elibuhlungu, ikhanda elikhanyayo, noma izinguquko kumbono wakho.

Dukwehlisa ukugeleza kwegazi kuya enhliziyweni nasenhliziyweni. Thola usizo oluphuthumayo uma unesihlungu esifubeni, uphefumula kanzima, uzizwa unesiyezi, noma uzizwa sengathi ufuna ukudlula emhlabeni.

A isimo esibizwa ngokuthi yi-reversible posterior leukoencephalopathy syndrome (RPLS). Shayela umhlinzeki wakho wezokunakekelwa kwezempilo ngokushesha uma uthola ikhanda elibuhlungu, ukuxhuzula, ukudideka, ukuguquka kombono, noma izinkinga zokucabanga

Risk yezinkinga zokuphulukisa isilonda. Amanxeba kungenzeka angapholi kahle ngesikhathi sokwelashwa kweRegorafenib. Tshela umhlinzeki wakho wezokunakekelwa kwezempilo uma uhlela ukuhlinzwa ngaphambi kokuqala noma ngesikhathi sokwelashwa ngeRegorafenib.

Should Kufanele uyeke ukuthatha iRegorafenib okungenani amasonto amabili ngaphambi kokuhlinzwa okuhleliwe.

▪ Umhlinzeki wakho wezokunakekelwa kwempilo kufanele akutshele ukuthi ungaqala nini ukuthatha iRegorafenib futhi ngemuva kokuhlinzwa.

Imiphumela emibi kakhulu neRegorafenib ifaka phakathi izinhlungu ezibandakanya indawo yesisu (isisu); ukukhathala, ubuthakathaka, ukukhathala; isifo sohudo (ukunyakaza kwamathumbu kaningi noma okuxekethile); ukuncipha kokudla; ukutheleleka; ukushintsha kwezwi noma ukushaqeka; ukwanda kokuhlolwa okuthile kokusebenza kwesibindi; imfiva; ukuvuvukala, ubuhlungu nokubomvu kocwecwe emlonyeni wakho, emphinjeni, esiswini, nasemathunjini (mucositis); nokwehlisa isisindo.

I-AASraw ingumkhiqizi oqeqeshiwe weRegorafenib.

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Ngigcina kanjani futhi / noma ngilahle iRegorafenib?

♦ Gcina amaphilisi esitsheni sokuqala ekamelweni lokushisa. Gcina ikepisi livalekile. Musa ukukhipha ikhekhe le-antimoisture noma iphakethe.

Ow Phonsa noma iyiphi ingxenye engasetshenziswanga emasontweni ayisikhombisa ngemuva kokuvula ibhodlela.

♦ Gcina endaweni eyomile. Ungagcini endlini yokugezela.

Gcina zonke izidakamizwa endaweni ephephile. Gcina yonke imishanguzo ingafinyeleli ezinganeni nasezifuyweni.

Ow Lahla izidakamizwa ezingasetshenziswanga noma eziphelelwe yisikhathi. Ungafaki ithoyilethi noma uthele umsele ngaphandle uma utshelwa ukuthi wenze njalo. Buza nosokhemisi wakho uma unemibuzo mayelana nendlela engcono yokukhipha izidakamizwa. Kungaba nezinhlelo zokubuyisa izidakamizwa endaweni yakho.

 

Regorafenib

 

Izinkomba zesikhathi esizayo of Regorafenib

Eminyakeni emihlanu ngemuva kokuvunywa kwayo, i-regorafenib ihlala iyisidakamizwa esinokuphathwa okulinganiselwe kwemitholampilo. Ukusetshenziswa okuvunyelwe kumdlavuza we-colorectal, i-GIST ne-HCC kungokwesifo se-metastatic esithuthukile kuphela. Kuhlanganiswe nezindleko eziphezulu, okwamanje kunenzuzo encane yomtholampilo yeziguli. Ngaphezu kwalokho, kwenziwa izilingo ezihlukile ukuze kuchazwe njengendlela entsha yokwelashwa. Izinkomba zesikhathi esizayo zalo muthi zifaka ukuphathwa kwe-osteosarcoma. Isivivinyo se-placebo esilawulwa kabili, esimpumputhe kabili eFrance sikhombise ukwanda kokusinda okungenazinqubekela phambili ngesici se-3 ezigulini ezine-metastatic osteosarcoma ezihluleke yonke imishanguzo yokwelashwa. Ngokucindezelayo, le mininingwane emisha ikhombisa inzuzo kwisifo se-metastatic esithuthukile njengesinqumo sokugcina, ngokufana nakho konke ukusetshenziswa kwamanje okugunyaziwe.

Idatha yakamuva iphakamisa ukuthi kungenzeka kube nomphumela we-synergic phakathi kwe-regorafenib kanye ne-immune checkpoint inhibitors, njengoba kukhonjisiwe esivivinyweni se-REGONIVO.Isivivinyo sesigaba se-Ib ngokuqhathanisa i-regorafenib nenhlanganisela yaso ne-nivolumab ezigulini ezinomdlavuza ophakeme wesisu noma umdlavuza we-colorectal, ikhombisile izinga lokuphendula le-38% (I-44% kumdlavuza wesisu kanye no-36% kumdlavuza obala) kanye nephrofayili yemiphumela ebekezelelekayo eqenjini elihlanganayo. Le nzuzo ethokozisayo ingabangelwa ukunciphisa ama-macrophage ahlobene nesimila yi-regorafenib, okwandisa ukuzwela kwe-tumour ku-nivolumab. Njengamanje, isilingo sesigaba II se-REGONIVO siyaqhubeka futhi kungekudala singasekela le mbono. Ngokwengeziwe, isivivinyo somtholampilo sesigaba sesibili sesibili sikhombisile ukuthi i-regorafenib ingcono kune-lomustine ku-glioblastoma ethuthukile futhi ebuyile.Isivivinyo se-REGOMA, e-Italy, sikhombise ukuthuthuka okuphawulekayo ekusindeni jikelele (isilinganiso sobungozi 0.50; isikhawu sokuzethemba esingu-95-0.33; log-rank p = 0.75) uma kuqhathaniswa nokwelashwa kwe-lomustine.

Izifundo ze-REVERSE zenziwe nge-regorafenib ne-cetuximab ekwelapheni umdlavuza we-metastatic colorectal. Imiphumela etholwe ngokulandelana kokusetshenziswa kwemithi enjalo ekwelapheni lo mdlavuza iphakamisa ukuthi ukuhleleka okuhle kungaba ukuphathwa kokuqala kwe-regorafenib kulandele i-cetuximab, ehlukile kunqubo evamile esetshenziswayo njengamanje. Imiphumela ikhombise ukuthuthuka kokusinda okuphelele kweziguli futhi inzuzo yabonakala iqhutshwa kakhulu ngomsebenzi omkhulu we-cetuximab kune-regorafenib njengokwelapha kwesibili.

Ukuhlanganiswa ukuqulwa kwe-regorafenib i-monotherapy kumdlavuza wesisu ikhombise ukuthi lo muthi ubekezeleleke kahle nokuthi bekungekho monakalo ezingeni lempilo yeziguli uma kuqhathaniswa nalabo abathola i-placebo nokuthi bekungabonakali kunomthelela omubi ngokweqile kuleyo mingcele yobuthi. Amaphrojekthi ocwaningo aqhakambisa ukuthi amazinga ayisisekelo obuhlungu, isifiso sokudla, ukuqunjelwa, nokusebenza komzimba kutholakale njengezici ezibalulekile zokubikezela ukusinda. Futhi, lolu cwaningo lubonise ukuthi i-regorafenib ibinomsebenzi omkhulu endaweni yokugcina yokusinda engena phambili. Ngaphezu kwalokho, isigaba II Isivivinyo se-REDOS senziwa kusuka ngo-2015–2018 futhi ababhali bakhombisa ukuthi isu lokukhuphuka komthamo le-regorafenib liyindlela efinyelelekayo kucebo elijwayelekile le-regorafenib dosing lika-160 mg / ngosuku, ikakhulukazi ezigulini ezinomdlavuza we-metastatic colorectal. Kutholakale nokuthi iziguli ezelashwa ngomthamo wokukhuphuka zinemvamisa ephezulu yokwelashwa kwangemva kokuqhubekela phambili kanye nokusinda isikhathi eside ngokwenombolo.

Mayelana nokubekezeleleka kwe-regorafenib lapho uqashelwe ukwelapha umdlavuza we-colorectal, imininingwane elinganiselwe iyatholakala ngokubekezelelana kubantu asebekhulile abagulayo, futhi isinqumo kufanele senziwe ngokubheka inzuzo yokusinda ephansi kanye nephrofayili yobuthi. Ngokubheka lesi sidakamizwa ekwelashweni kwe-HCC, amaphrojekthi ocwaningo agcizelela ukuthi kukhona iphrofayili yokubekezelelana eyamukelekayo nokuthi i-regorafenib inikeza inzuzo yokusinda. Ukwelashwa kwe-GIST, ababhali abaningana bathi i-regorafenib ibekezelelwe kahle ngaphandle kobuthi obungalindelekile.

Ucwaningo olwengeziwe luyadingeka ukuthola ukuthi yiziphi iziguli ezingazuza kakhulu kulo muthi. Kusukela ngo-2019, izilingo eziqhubekayo zihlola ukuthi i-regorafenib ingayithuthukisa imiphumela kuma-sarcomas ethambile, njenge-osteogenic sarcoma, liposarcoma, i-Ewing sarcoma ne-rhabdomyosarcoma.

 

Isiphetho

Naphezu kweminyaka engu-5 yokuvunywa nokuthembiswa kwe-pharmacodynamics, i-regorafenib ikhombise inzuzo elinganiselwe, kepha ebaluleke ngokwezibalo, ezinhlobonhlobo zamathumba aqinile. Izinkomba ezinelebula ziqukethe umdlavuza we-colorectal, i-GIST ne-HCC. Izilingo zesigaba sesibili ezithuthukisiwe zikhombise ukuthuthuka okukhulu ekusindeni komdlavuza wesisu, i-glioblastoma kanye ne-osteosarcoma, engakhombisa ukufakwa kwesikhathi esizayo ezinkomba ezinelebula.

Ukwelashwa kokuhlanganiswa kwama-immune checkpoint inhibitors kukhonjisiwe njengokuzuzisayo esivivinyweni sesigaba sokuqala, futhi kwenziwa izivivinyo zesigaba II. Njengamanje, i-regorafenib iyaphenywa nakweminye imidlavuza. Imiphumela emibi eminingi yomuntu ngamunye ingasetshenziswa njengezimpawu zemiphumela engcono ngokwelashwa. Phakathi kwalabo, i-hand-foot syndrome ne-hypothyroidism yizona ezihlobene kakhulu nokusinda okuthuthukile. Ngokufingqa, ucwaningo lukhombisile ukuthi i-regorafenib ingakuthuthukisa kakhulu ukusinda ngokubekezelelana okwamukelekayo ezinhlakeni ezahlukahlukene eziqinile.

I-AASraw ingumkhiqizi oqeqeshiwe weRegorafenib.

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Izikhombo

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[2] UThangaraju P, Singh H, Chakrabarti A. Regorafenib: inoveli tyrosine kinase inhibitor: ukubuyekezwa okufushane kwamandla ayo okwelapha ekwelapheni i-metastatic colorectal carcinoma kanye nezicubu zomzimba ezithuthukisiwe zamathumbu. Umdlavuza WaseNdiya J. 2015; 52: 257-60.

[3] I-Grünewald FS, i-Prota AE, i-Giese A, i-Ballmer-Hofer K. Ukuhlaziywa kokusebenza kwesakhiwo se-VEGF ukwamukela ukusebenza kanye nendima yama-coreceptors ekusayineni kwe-angiogenic. Amaphrotheni ama-Biochim Biophys Acta Proteomics. 2010; 1804: 567-80.

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[7] UAscierto PA, uKirkwood JM, uGrob JJ, et al. Indima yokuguqulwa kwe-BRAF V600 ku-melanoma. J Ukuhumusha Med. 2012; 10: 85.

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