Umdlavuza we-Colorectal ungenye yezimila eziyingozi ezivame kakhulu. E-China, izehlakalo zomdlavuza we-colorectal zikleliswe endaweni yesi-4 neyesi-3 phakathi kwabesilisa nabesifazane, ngokulandelana. Ukungena esimweni sesifo esithuthukile, isu lokwelapha lalezi ziguli ukwelapha okuphelele okusekelwe ngamakhemikhali. Uma kuqhathaniswa nokwelashwa okungcono kakhulu okusekelayo, kungandisa kakhulu isikhathi sokuphila futhi kuthuthukise izinga lempilo. Eminyakeni emibili edlule, ngokujula kocwaningo oluqondiswe kumangqamuzana omdlavuza, ukusebenza kwezidakamizwa ezihlosiwe kuba ngcono futhi kuba ngcono, futhi imiphumela emibi mincane, ukuze odokotela neziguli babe nezinketho eziningi zokwelapha. Ake sibheke i-colorectal Yiziphi izindlela zokwelapha ezikhona manje zomdlavuza?
Uhlelo lokwelashwa komdlavuza we-Colorectal
(1) It is recommended to detect the gene status of isisu K-ras, N-ras and BRAF before treatment, and EGFR is not recommended as a routine test item.
(2) Ukwelapha ngamakhemikhali okuhlanganisiwe kufanele kusetshenziswe njengokwelashwa komugqa wokuqala nowesibili ezigulini ezinomdlavuza we-metastatic colorectal ongabekezelela ukwelashwa ngamakhemikhali. Imithi elandelayo yokwelapha ngamakhemikhali iyatuswa: I-FOLFOX noma i-FOLFIRI, noma ihlanganiswe ne-cetuximab (enconyelwe iziguli ezinohlobo lwasendle lwe-K-ras, N-ras, BRAF gene), CapeOx, FOLFOX noma FOLFIRI, noma kuhlanganiswe ne-bevacizumab.
(3) Iziguli ezinokwelashwa ngamakhemikhali okungaphezu komugqa wesithathu zinconywa ukuthi zizame izidakamizwa eziqondiwe noma zihlanganyele ekuhlolweni komtholampilo. Ezigulini ezingasebenzisi izidakamizwa ezihlosiwe ekwelashweni komugqa wokuqala nowesibili, i-irinotecan ehlanganiswe nokwelashwa kwezidakamizwa okuhlosiwe nakho kungacatshangelwa.
(4) Kunconywa ukuhlolwa kweRegofinil noma kwemitholampilo yeziguli ezehlulekile kulayini wesithathu nangaphezulu kokwelashwa okujwayelekile. Ezigulini ezingasebenzisi imishanguzo ekhonjiwe ekwelashweni kolayini wokuqala nolwesibili, i-irinotecan ihlangene ne-cetuximab (enconyelwe uhlobo lwasendle K-ras, N-ras, izakhi zofuzo ze-BRAF) nayo ingabhekwa.
(5) Ezigulini ezingakwazi ukubekezelela i-chemotherapy yokuhlanganiswa, uhlelo lwe-fluorouracil + calcium folinate noma i-capecitabine umuthi owodwa noma izidakamizwa ezihlosiwe ziyanconywa. Iziguli ezinomdlavuza osezingeni eliphezulu ezingafanele i-fluorouracil + calcium leucovorin regimen zingacabanga ukwelashwa nge-single-agent nge-raltrexone.
(6) Iziguli ezinesifo esizinzile ngemuva kwezinyanga ezine kuya kwezingu-4 zokwelashwa okunciphisayo kepha azinalo ithuba lokuphinda kutholakale i-R6 zingacabanga ukungena ekwelashweni kwesondlo (njengokusebenzisa i-fluorouracil + calcium leucovorin enobuthi obuncane, noma i-capecitabine umuthi owodwa ohlangene noma ukumisa ukwelashwa kwesistimu) ukunciphisa ubuthi be-chemotherapy ehlanganisiwe.
(7) Ezigulini ezine-BRAF gene V600E mutation, uma isimo esijwayelekile singcono, i-FOLFOXIRI noma ukwelashwa komugqa wokuqala kuhlanganiswe ne-bevacizumab kungabhekwa.
(8) Uma isimo esijwayelekile noma ukusebenza kwesitho somzimba kubi kakhulu ezigulini ezithuthukile, kunconywa ukwelashwa okuhle kakhulu okusekelayo.
(9) Uma i-metastasis ikhawulelwe esibindini kanye / noma emaphashini, bheka imigomo yokwelashwa kwe-metastasis yesibindi kanye ne-lung metastasis.
(10) Ezigulini eziphindelela endaweni yomdlavuza wesisu, ukuhlolwa okuhlukahlukene kuyanconywa ukuze kunqunywe ukuthi zinalo yini ithuba lokukhishwa kabusha noma i-radiotherapy futhi. Uma kufanele kuphela i-chemotherapy, izimiso ezingenhla zokwelashwa kwezidakamizwa ezigulini ezithuthukile ziyamukelwa.
Ukukhethwa kwamakhemikhali ezigulini ezinomdlavuza onobala
Imithi yokwelashwa ngamakhemikhali esetshenziselwa ukwelapha umdlavuza osezingeni eliphezulu ifaka phakathi: i-fluorouracil (kufaka phakathi nomlomo
ICapecitabine), i-oxaliplatin ne-irinotecan.
One
Ukwelashwa kokungeniswa
1. Uhlelo lwezidakamizwa ezintathu
I-FOLFOXIRI [23]: irinotecan 165 mg / m2, ukumnika okufaka emithanjeni, i-d1; i-oxaliplatin 85 mg / m2, ukumnika okufaka emithanjeni, i-d1; I-LV 400 mg / m2, ukumnika okufaka emithanjeni, i-d1; I-5-FU 1 600 mg / (m2 · d) × 2 d ukumnika okufaka emithanjeni okuqhubekayo (inani eliphelele elingu-3 200 mg / m2, ukumnika amahora angama-48), kusukela ngosuku lokuqala. Phinda njalo emavikini amabili.
2. Uhlobo lwemithi emibili
(1) Izinhlelo ezisekelwe ku-Oxaliplatin, njenge-FOLFOX ne-CapeOx, zibona ukwelashwa kwe-adjuvant yomdlavuza wamathumbu.
(2) Uhlobo olususelwa ku-Irinotecan: I-FOLFIRI: irinotecan 180 mg / m2, ukumnika okufaka emithanjeni ngamahora ama-2, i-d1; I-LV 400 mg / m2, ukumnika okufaka emithanjeni amahora ama-2, i-d1; I-5-FU 400 mg / m2, umjovo we-intravenous bolus, i-d1, bese kuba ngu-2 400 mg / m2, ukumnika okufaka ngaphakathi okuqhubekayo amahora angama-46 kuye kwangama-48. Phinda njalo emavikini amabili.
3. Uhlobo lwemithi olulodwa
Uma isiguli singakwazi ukubekezelela ukwelashwa okuqinile kokuqala, i-5-FU / LV noma i-capecitabine infusion (bona i-adjuvant therapy ngemininingwane ethile) noma i-agent eyodwa irinotecan (125 mg / m2 irinotecan, ukumnika okufaka emthanjeni 30 ~ 90 amaminithi, d1, d8, okuphindiwe njalo emavikini ama-3; noma i-irinotecan 300-350 mg / m2, ukumnika okufaka emthanjeni imizuzu engu-30-90, i-d1, iphindaphindwe njalo emavikini amathathu) Noma i-irinotecan 3 mg / m180, ukumnika okufaka emthanjeni amahora ama-2, i-d2, iphindaphindwe njalo emavikini ama-1.
Ngemuva kokwelashwa okungenhla, uma isimo esijwayelekile sesiguli singakathuthuki, kufanele kunikezwe ukwelashwa okusekelayo okungcono kakhulu.
Two
Ukwelashwa kwesondlo
Isivivinyo se-OPTIMOX1 sikhombisile ukuthi ezigulini ezinomdlavuza we-metastatic colorectal ezithola i-FOLFOX njengokwelashwa komugqa wokuqala, ukusetshenziswa okuphakathi kwamasu we-oxaliplatin "stop and go" kunganciphisa i-neurotoxicity kodwa akuphazamisi ukusinda [26]. Ngakho-ke, ngemuva kwezinyanga ezi-3 kuya kwezi-6 zokuhlanganiswa kwamakhemikhali ama-dual-agent, njengesifo i-CR / PR / SD, i-oxaliplatin noma i-irinotecan enezimpawu ezingezinhle kakhulu zinganqanyulwa, kanti ezinye izindlela zokwelashwa kwezidakamizwa ku-regimen ziyaqhubeka. Kuze kube yilapho isimila siqhubeka, ukusinda okungenazinqubekela phambili kunganwetshwa, kepha inzuzo yokusinda iyonke ayicaci.
Three
Okwesibili, izinketho zokwelashwa ngamakhemikhali okwesithathu nokwalandela
Ukukhethwa kwe-chemotherapy yomugqa wesibili kuncike ohlelweni lokwelashwa komugqa wokuqala. Izinhlelo ezisekelwe ku-oxaliplatin nezisuselwa ku-irinotecan zingaba ulayini wokuqala nowesibili komunye nomunye. Ngokwesimo somzimba sesiguli, khetha umuthi owodwa noma uhlelo lokwelashwa okuhlanganisiwe.
Iziguli ezine-chemotherapy engaphezulu kwesithathu zinconywa ukuthi zizame izidakamizwa ezihlosiwe noma zibambe iqhaza ezivivinyweni zomtholampilo. Ezigulini ezingasebenzisi imishanguzo ekhonjiwe ekwelashweni kolayini wokuqala nolwesibili, i-irinotecan kuhlangene nokwelashwa kwezidakamizwa okuqondisiwe nakho kungabhekwa.
Ukwelashwa okuhlosiwe komdlavuza onobala
Uhlu lokuhlosiwe kanye ne- immunotherapy imishanguzo yomdlavuza onemibala evunyelwe kuze kube manje ekhaya nakwamanye amazwe.
1. IBevacizumab
Igama elijwayelekile: An Wei Ting
Igama lesiNgisi: Avastin
Igama lesakhiwo samangqamuzana: Bevacizumab
Izinkomba eziyinhloko: umdlavuza obala
Umsuka: Roche
I-Bevacizumab (i-Avastin®) i-antibody monoclonal antibody ephindaphindekayo. Yavunywa yi-FDA ngoFebhuwari 26, 2004, futhi kwakuyisidakamizwa sokuqala esivunyelwe e-United States ukucindezela i-tumor angiogenesis.
Ukusebenza kwe-bevacizumab njenge-ejenti eyodwa kuphansi, futhi ngokuvamile kunconywa ukuthi kusetshenziswe kuhlanganiswe ne-chemotherapy.
Uhlobo lwemithi ehlanganisiwe ye-chemotherapy: IFL, FOLFIRI, FOLFOX kanye neCapeOX; imithamo esetshenzisiwe: 5 mg / kg (uhlobo lwamaviki amabili) kanye no-2 mg / kg (uhlobo lwamaviki amathathu).
Inhlanganisela ye-IFL ne-bevacizumab ekwelashweni komdlavuza we-colorectal osezingeni eliphakeme inyuse i-OS kusuka ezinyangeni eziyi-15.6 kuya ezinyangeni ezingama-20.3 (isifundo se-AVF2107).
I-Bevacizumab ihlanganiswe nohlelo lwe-FOLFIRI njengokwelashwa komugqa wokuqala, izinga elisebenzayo lalingu-58.7%, i-PFS kwakuyizinyanga eziyi-10.3 (ucwaningo lwe-FIRE3).
I-Bevacizumab ihlanganiswe ne-FOLFOX noma i-FOLFIRI njengokwelashwa komugqa wokuqala, i-PFS ifinyelele ezinyangeni eziyi-11.3, i-OS yafinyelela ezinyangeni ezingama-31.2 (isifundo se-CALGB80405).
2. ICetuximab
Igama elijwayelekile: Erbitux
Igama lesiNgisi: CETUXIMAB SOLUTION FOR INFUSION
Igama lesakhiwo samangqamuzana: Cetuximab
Izinkomba eziyinhloko: umdlavuza obala
Indawo Yomsuka: Merkelion, Germany
Ngaphambi kokwelashwa nge-cetuximab, uhlobo lwe-RAS kufanele luhlolwe ngaphambi kokuba zonke iziguli zohlobo lwasendle zisebenzise i-cetuximab. Izinga elisebenzayo le-cetuximab lingama-20% kuphela, futhi kuvame ukuthi kunconyelwe ukuthi lisetshenziswe ngokuhlangana ne-chemotherapy.
FOLFIRI futhi FOLFOX; isilinganiso: 400mg / m2 250mg / m2 ngeviki ngemuva komthamo wokuqala.
Ezigulini zohlobo lwe-RAS zasendle, i-cetuximab ehlanganiswe ne-FOLFIRI regimen noma i-FOLFOX regimen iletha iPFS ne-OS ende ukwedlula i-chemotherapy kuphela.
3. Regafini
Igama elijwayelekile: Baivango
Igama lesiNgisi: regorafenib
Igama lesakhiwo seMolekyuli: Regefenib
Izinkomba eziyinhloko: umdlavuza we-metastatic colorectal
Indawo Yomsuka: Bayer Corporation
Abantu abasebenzayo: NgoSepthemba 2012, uRegefini wagunyazwa yi-FDA ukwelapha umdlavuza wamakholoni osezingeni eliphezulu. NgoMeyi 2017, iCFDA yaseChina nayo ivume i-regorafenib ekwelashweni kwe-fluorouracil, i-oxaliplatin, ne-irinotecan-based chemotherapy kanye ne-anti-VEGF therapy 1. Iziguli ze-Anti-EGFR therapy (uhlobo lwe-RAS zasendle) ezinomdlavuza we-metastatic colorectal (mCRC).
4.I-Panitumumab (i-panitumumab)
Igama elijwayelekile: Viktibi
Igama lesiNgisi: Erbitux cetuximab
Igama lesakhiwo samangqamuzana: panitumumab
Izinkomba eziyinhloko: umdlavuza we-metastatic colorectal
Indawo Yomsuka: American Amgen
Imithi yokwelapha umdlavuza we-Colorectal I-Vectibix (panitumumab) kanye ne-panitumumab zingamasosha omzimba okuqala enziwe umuntu ngokugcwele aqondise isamukeli se-epidermal growth factor (EGFR). NgoJulayi 2005, i-Panitumumab yathola imvume ye-FDA esheshayo. Ekupheleni kuka-2005, u-Amgen kanye nozakwabo u-Abgenix ngokuhlanganyela bathumela isicelo selayisense salo mkhiqizo ku-FDA ukuze kwelashwe umdlavuza we-metastatic colorectal ngemva kokwehluleka kwe-chemotherapy.
I-5.Ziv-aflibercept (i-Abercept)
Igama lesiNgisi: Zaltrap (ziv-aflibercept yesisombululo sokumnika)
Igama lesakhiwo samangqamuzana: Abecip
Izinkomba eziyinhloko: umdlavuza we-metastatic colorectal
Umsuka: Sanofi
I-Abecip yamukelwa yi-US FDA yokwelashwa komdlavuza osezingeni eliphezulu ngo-2012. Yisidakamizwa se-chimeric protein esivimbela ukulethwa kwezakhi zomzimba ngokuvimbela ukukhula kwe-vascular endothelial factor VEGF, ngaleyo ndlela kuvimbele ukwanda kwesimila.
I-Aflibercept ibophezela ekusakazeni i-VEGF emzimbeni futhi isebenza njenge- "VEGF trap". Ngakho-ke, zivimbela ukusebenza kwama-vascular endothelial growth factor subtypes i-VEGF-A ne-VEGF-B kanye ne-placental factor factor (PGF), ngokulandelana, futhi kuvimbela ukukhula kwemithambo yegazi emisha kuma-chorionic cysts noma kwizicubu. Kungashiwo ukuthi inhloso ye-Aflibercept "ukulamba" izicubu zomzimba.
6. URamolimumab (uCyramza)
Igama lesiNgisi: ramucirumab
Igama lesakhiwo seMolekyuli: Remolumumab
Izinkomba eziyinhloko: umdlavuza obala
Umsuka: U-Eli Lilly neNkampani
I-Cyramza yagunyazwa yi-US FDA ngo-2014 ukwelapha umdlavuza wesisu, umdlavuza we-colorectal kanye nomdlavuza wamaphaphu ongewona omncane.
Njengoba izicubu zesimila zikhula, kuzobhekana nenqubo ye-angiogenesis, okungukuthi, ukwakheka kwemithambo yegazi emisha ezungeze izicubu zesimila ukuhambisa umsoco kumaseli wesimila. Ngakho-ke, ukuvimbela le nqubo kungavimbela ukwanda kwezimila eziningi.
ICyramza isidakamizwa sokulwa nesifo somzimba esisodwa, esivimbela kakhulu ukwakheka kwemithambo yegazi emisha ezungeze isimila futhi sivimbele ukuhanjiswa kwezakhi zomzimba kulesisibopho ngokubophezela kwi-vascular endothelial growth factor receptor (VEGFR2), ngaleyo ndlela kuvimbele ukwanda kwesimila.
7. I-Fruquintinib
Igama lomkhiqizo: Aiyoute
Izimpawu ezisebenzayo: Kuvunyelwe eChina ngoSepthemba 5 ekwelashweni kwe-fluorouracil yangaphambilini, i-oxaliplatin kanye ne-irinotecan-based chemotherapy, kanye nokwelashwa kwangaphambilini noma okungafanelekile nge-anti-vascular endothelial grow factor (VEGF) 1. Iziguli ezine-metastatic CRC ziphathwe ngemithi yokulwa i-epidermal growth factor receptor (EGFR) (uhlobo lwasendle lwe-RAS).
7.i-opdivo
Igama lesiNgisi: nivolumab
Igama lesakhiwo samangqamuzana: nivolumab
Izinkomba eziyinhloko: umdlavuza obala
Indawo Yomsuka: Bristol-Myers Squibb
Ucwaningo nokuthuthukiswa okuhlangene kwe-Ono kanye ne-Bristol Myers Squibb (BMS), ngoJulayi 2014 yi-Japanese Pharmaceutical and Medical Devices Agency (PMDA), December 2014 yi-US Food and Drug Administration (FDA) Egunyazwe, egunyazwe yi-European Medicines Agency ( EMA) ngoJuni 2015, egunyazwe yi-China Food and Drug Administration (CFDA) ukuze ikhangiswe ngoJuni 2018, futhi idayiswa yi-Ono Pharmaceuticals e-Japan, Bristol-Myers Squibb e-United States, Ithengiswa eYurophu nase-China ngaphansi komkhiqizo. Igama elithi Odivo®.
Inqubekela phambili yakamuva yokwelashwa komdlavuza wobala
1) I-TAS-102 (iLonsurf)
I-TAS102 iyisidakamizwa somlomo se-chemotherapeutic esakhiwe nge-anti-tumor nucleoside analog FTD (trifluorothymidine, trifluridine) kanye ne-thymidine phosphorylase inhibitor TPI.
I-mPFS yeqembu le-TT-B elaphathwa nge-TAS102 + bevacizumab yayizinyanga eziyi-9.2, ezaziphakeme kakhulu kunezinyanga eziyi-7.8 zeqembu le-capecitabine + bevacizumab CB elaliphethwe ngokwesiko. Ukusinda okungenakho ukuqhubeka. Kulindeleke ukuthi kube yindlela yokwelashwa yomugqa wokuqala kulezi ziguli.
2) Ziyini izinzuzo zokwelashwa ngempumelelo ekuhlanganisweni kwezidakamizwa ezintathu?
Inhlanganisela ye-encorafenib, i-binimetinib ne-cetuximab yeziguli eziguqukayo ze-BRAF inguquko enkulu, ngoba ucwaningo oluningi lukhombisile ukuthi inhlanganisela ye-BRAF inhibitors kanye ne-MEK inhibitors ezigulini eziphikisayo, kungabonakala ukuthi izinga lokuphendula lidlula u-30%, okungazwakali ka.
Imininingwane yakamuva ethunyelwe kwi-2018 World Congress of Gastrointestinal Cancer ikhombisa ukuthi inhlanganisela yezidakamizwa ezintathu ayinayo kuphela izinga lokuphendula eliphezulu, kepha futhi ine-PFS ne-OS ende. Kungakho izilingo zenziwa ekwelashweni komugqa wokuqala. Kuyathakazelisa ukuthi le triplet ayinazo izidakamizwa eziqondiswe ku-cytotoxic. Lokhu kukhombisa ukuthi ingakhomba ngobuhlakani ama-molecule we-tumor futhi ikhiqize imiphumela ebalulekile yomtholampilo ngaphandle kokwenza ubuthi obuningi.
3) Iyini inqubekela phambili ye-immunotherapy?
Ngezicubu ze-MSI-H, inhlanganisela ye-nivolumab ne-ipilimumab inethuba lokuthola ukwelashwa komugqa wokuqala, ngoba idatha yokusebenza ibonakala ikholisa kakhulu.
Ngezicubu ezizinzile ze-microsatellite, kufanele sihlanganise i-immunotherapy ne-chemotherapy ejwayelekile-FOLFOX / bevacizumab ngokuhlangana ne-nivolumab.
