I-Immunotherapy isebenzisa izidakamizwa ukusiza amasosha omzimba abone kangcono futhi abhubhise amangqamuzana omdlavuza. I-Immunotherapy ingasetshenziswa ukwelapha iziguli ezinomdlavuza we-colorectal osezingeni eliphezulu.
Isithiyo sokuhlola izivikeli mzimba
Ingxenye ebalulekile yamasosha omzimba yikhono layo lokuzivikela ekuhlaseleni amaseli ajwayelekile omzimba. Ngalokhu, isebenzisa amaprotheni "wokuhlola" kumaseli omzimba, enza njengokushintshwa okudinga ukukhanyiswa (noma ukuvulwa) ukuqala ukuphendula komzimba.
Amaseli womdlavuza kwesinye isikhathi asebenzisa lezi zindawo zokuhlola ukunqanda amasosha omzimba ekuwahlaseleni. Kodwa-ke, izidakamizwa ezibhekiswe kulezi zindawo zokuhlola zinamathemba amakhulu njengezindlela zokwelashwa komdlavuza.
Izidakamizwa ezibizwa ngokuthi i-checkpoint inhibitors zingasetshenziswa kubantu amaseli omdlavuza obala ngokobulili ahlole ukuthi anezinguquko ezithile zofuzo, njengamazinga aphezulu okungazinzi kwe-microsatellite (MSI-H), noma olunye lwezinhlobo zezinguquko zemfuza zokulungisa okungafani (MMR).
Le mithi isetshenziswa kubantu abanomdlavuza osakhula ngemuva kokwelashwa ngamakhemikhali. Zingase futhi zisetshenziselwe ukwelapha abantu abanomdlavuza ongakwazi ukususwa ngokuhlinzwa, ophindela emuva ngemva kokwelashwa (ukubuyisela kabusha) noma osusakazekele kwezinye izingxenye zomzimba (i-metastasis).
Kuvunyelwe immunotherapy izidakamizwa
I-PD-1 inhibitor igunyaziwe
I-Pembrolizumab (Pembrolizumab, Keytruda) kanye ne-nivolumab (i-Nivolumab, i-Opdivo) yizidakamizwa eziqondise i-PD-1, iphrotheni esemangqamuzaneni amasosha omzimba abizwa ngokuthi ama-T cell avame ukusiza Ukuvimbela lawa maseli ekuhlaseleni amanye amaseli emzimbeni. Ngokuvimbela i-PD-1, le mithi ingathuthukisa ukusabela komzimba kumaseli omdlavuza.
On May 24, 2017, the US FDA approved the PD-1 inhibitor pembrolizumab (Pembrolizumab, Keytruda) for the treatment of solid isisu patients with microsatellite highly unstable (MSI-H) / mismatch repair defects (dMMR), The tumor types cover 15 different malignant tumors, including colorectal cancer, small cell lung cancer, and cervical cancer.
Ngo-Agasti 2, 2017, i-US Food and Drug Administration (FDA) yavuma i-nivolumab (Navumab, Opdivo) ekwelashweni kwe-fluorouracil, oxaliplatin, ne-irinotecan. I-Microsatellite enesifo esingazinzile (MSI -H) Ukwelashwa komdlavuza we-metastatic colorectal kubantu abadala noma ezinganeni (≥12 iminyaka) noma ukukhubazeka okungahambi kahle kokulungisa (dMMR).
Kuvunyelwe i-CTLA-4 inhibitor
I-Ipilimumab (Yervoy) esinye isidakamizwa esingaqinisa ukuphendula komzimba. Ngeke isetshenziswe yodwa. Idinga ukuhlanganiswa ne-nivolumab, evimba i-CTLA-4, engenye yamaprotheni kuma-T cell.
Icala eliphumelelayo le-MSI-High (MSI-High) mCRC ukusetshenziswa ngokuhlanganyela kwe-nivolumab ne-ipilimumab, eyahlolwa ocwaningweni lweSigaba II CheckMate142. Ukwelashwa kokuhlanganiswa kukhombise i-ORR (isilinganiso sokuphendula ngenhloso) yama-49%, kanti ezi-5 kweziguli eziyi-119 zine-CR (impendulo ephelele) kanye nama-53 PR (impendulo engaphelele). Iziguli eziningi (n = 82) phambilini bezithole i-fluorouracil, i-oxaliplatin ne-irinotecan. Kulezi ziguli, i-ORR yayingu-46%, ama-3 CRs nama-PR PR angama-35.
Ngokwedatha ye-CheckMate-142, i-FDA ivume inhlanganisela (i-Nivolumab + Ipilimumab) yokwelashwa kweziguli ezindala nezingane ezineminyaka engu-12 ubudala nangaphezulu, kufaka phakathi iziguli ze-mCRC ezine-MSI-H noma amaphutha okulungisa okungafani kahle (dMMR), Lezi ziguli zithuthukile ngemuva kokwelashwa nge-fluorouracil, i-oxaliplatin ne-irinotecan.
Ukuhunyushwa kokusetshenziswa kwe-MSI / dMMR ekwelashweni okucacile
I-MSI ibhekisa ekulahlekelweni kwezakhi zofuzo zokulungisa izinto ezingafani ezibangelwa yi-DNA methylation noma ukuguqulwa kwezakhi zofuzo, okuholela ekuguqulweni kobude bokulandelana okuphindwayo kwe-microsatellite. Ucwaningo luthole ukuthi i-MSI-H iyi-biomarker ebalulekile yamathumba afanele i-immunotherapy.
I-MSI ukungazinzi kwe-microsatellite, i-MMR (ukulungisa okungafani kahle) kubhekisa emsebenzini wokulungisa ukungalingani kofuzo. Isakhi sofuzo sokulungisa okungafani (isakhi sofuzo seMMR) singabonisa amaprotheni wokulungisa okungahambi kahle ngemuva kokubhalwa nokuhumusha. Uma ukulahleka kokuvezwa kwanoma iyiphi iprotheni ye-MMR kungadala ukukhubazeka emsebenzini wokulungisa okungafani kweseli, ukungafani kwesisekelo kunqubo yokuphindaphindeka kwe-DNA Ukulahleka komsebenzi wokulungisa kuholela ekuqongeleleni, okuholela ekwenzekeni kokungazinzi kwe-microsatellite (MSI). Cishe i-15% yomdlavuza obomvu ibangelwa indlela yeMSI.
I-PCR ingasetshenziswa ukuthola ubude bezingosi zesathelayithi (ama-microsatellites ayizimpinda ze-tandem zokulandelana kwe-DNA emifushane ku-genome ye-eukaryote) ku-tumor cell DNA, bese kuqhathaniswa ne-DNA yeseli evamile ehambisanayo. Ngokuthandwa kanye nokusetshenziswa kwe-NGS (Second Generation Sequencing), ngaphezu kokutholwa kwe-immunohistochemistry yendabuko kanye ne-PCR, isimo se-microsatellite singatholwa endaweni yesikhulumi se-NGS. Ukuze uqonde izikhungo zokuhlola izakhi zofuzo ze-NGS ezigunyaziwe ekhaya naphesheya, sicela uthintane no-400-626-9916.
Ngaphezu kwalokho, ama-tumor specimens (kufaka phakathi ama-specimens wokuhlinza nama-puncture specimens) angasetshenziselwa ukutholwa kwe-immunohistochemical kwezakhi zofuzo ezine ezingafani, kufaka phakathi: MLH1, MSH2, MSH6, ne-PMS2. Uma nje noma imaphi kulawa maprotheni amane engekho, isimila singaphansi kwe-dMMR, okuyiphutha lomsebenzi wokulungisa okungafani. Uma wonke amaprotheni amane evezwa kahle futhi isimila kuyi-pMMR, umsebenzi wokulungisa okungafani usuqediwe.
Ukuhlolwa kofuzo kokuhlolwa kombiko weMSI
Isithombe esilandelayo sikhombisa isiguli esivela kwi-Global Oncologist Network esitholakale sine-MSI-H ngemuva kokuhlolwa kwe-MSI yinkampani yokuhlola ulibofuzo lwasekhaya (400-626-9916). Lesi siguli sinenhlanhla enkulu futhi silungele i-immunotherapy.
Esinye isiguli esikwi-Global Oncologist Network sahlolwa kahle yi-US Keruis Gene (400-626-9916), futhi wonke amaprotheni amane ayene-positive (okusho ukuthi) isiguli sasiyi-pMMR, futhi sasingafanele i-Immunotherapy evunyelwe ngenhla .
Ukuchazwa kwemiphumela yokuhlolwa kokugcina kungahlukaniswa nge-MSS (ukuzinza kwe-microsatellite), i-MSI-L (ukungazinzi okuncane kwe-microsatellite) ne-MSI-H (ukungazinzi okuphezulu kwe-microsatellite). Ngokuvamile, i-dMMR ilingana ne-MSI-H, futhi i-pMMR ilingana ne-MSS ne-MSI-L.
Izindlela zokuqapha ukusetshenziswa kwe-PD-1 inhibitors
- Le mithi inikezwa njenge-infravenous (IV) infusions njalo emavikini amabili noma amathathu.
- Imiphumela emibi yale mithi ihlanganisa ukukhathala, ukukhwehlela, isicanucanu, ukulunywa, ukuqubuka, ukungathandi ukudla, ukuqunjelwa, ubuhlungu bamalunga kanye nohudo.
- Eminye imiphumela emibi kakhulu yenzeka kaningi. Kwesinye isikhathi, amasosha omzimba angahlasela ezinye izingxenye, mhlawumbe abangele izinkinga ezinkulu noma ezisongela ukuphila emaphashini, emathunjini, esibindini, izindlala ezikhiqiza ama-hormone, izinso, noma ezinye izitho.
- Ngesikhathi sokumnika, isimo somzimba sesiguli sidinga ukubhekwa ngesikhathi sangempela.
Izinyathelo zokuqapha zemithi ye-Ipilimumab
- Lo muthi usetshenziswa ne-nivolumab (Opdivo) ukwelapha umdlavuza obala ngokobulili, kepha awunakusetshenziswa wedwa. Inikezwa ukumfakelwa ngemithambo (IV), imvamisa njalo emavikini amathathu emijikelezweni yokwelashwa emi-3.
- Imiphumela emibi kakhulu yalo muthi ihlanganisa ukukhathala, isifo sohudo, ukuqubuka kanye nokulunywa.
- Uma usebenzisa lesi sidakamizwa, imiphumela emibi emibi ibonakala ijwayelekile kakhulu kunokusebenzisa ama-PD-1 inhibitors. Njengama-PD-1 inhibitors, lo muthi ungadala ukuthi amasosha omzimba ahlasele ezinye izingxenye zomzimba, ezingadala izinkinga ezinkulu ngamathumbu, isibindi, izindlala ezikhiqiza ama-hormone, izinzwa, isikhumba, amehlo, noma ezinye izitho. Kwabanye abantu, le miphumela emibi ingasongela impilo.
- Ngesikhathi sokumnika, isimo somzimba sesiguli sidinga ukubhekwa ngesikhathi sangempela.
Ungazikhetha kanjani izidakamizwa ze-immunotherapy kumdlavuza onobuhlungu?
Isazi somdlavuza we-colorectal cancer waseMelika uDkt Chiorean uthe, “IPembrolizumab noma i-nivolumab zithandwa kakhulu kwiziguli ezine-MSI-H. I-Nivolumab ehlangene ne-ipilimumab (i-CTLA-4 inhibitor) ayivamisile ukusetshenziswa. Ngicabanga umehluko i
s very small. Similarly, some people may argue that CTLA-4 may be better tolerated by the inhibitory response, but I also feel that the toxicity is significantly higher. ”
Dr. Messersmith said that when he needed to quickly obtain therapeutic effects, he used nivolumab and ipilimumab combination therapy. Adding ipilimumab can get an additional 15%–20% response rate. If the patient is symptomatic, it can be added. Even though this may increase adverse reactions, the treatment effect is even greater. This requires an assessment of the patient’s physical condition.
If patients and their families have difficulty in choosing an immunotherapy drug, they can seek domestic authoritative colorectal cancer experts for consultation through the Global Oncologist Network (+91 96 1588 1588) to determine the final, more suitable treatment plan.
