Imiphi imiphumela emibi ingabe udokotela wakho ubheke?
Njenganoma imuphi ukwelashwa, kunesimo esiphezulu futhi esihlaselayo. Ukugcizelela ukuthi i- immunotherapy isetshenziselwa ukuthuthukisa ukubikezela kwezinhlobo ezithile zomdlavuza njengemdlavuza engasemncane yamangqamuzana wamaphaphu, i-melanoma, umdlavuza wesangqamuzana we-renal, umdlavuza we-colon, ne-Hodgkin's lymphoma. Ngamanye amazwi, abantu banikezwa ithuba lesibili ekuphile ukuphila okunethezekile futhi okunethezeka-into eyenza ngokuqondile ukushintsha ukwelashwa komdlavuza.
Yiqiniso, ukuhlaziywa kwe-immunotherapy kuqala nje, futhi lokhu kuyindawo eguqukayo futhi ejabulisayo kakhulu ekucwaningweni komdlavuza nasekunakekeleni okwamanje.
Ngalokho, njengoba abantu abaningi belashwa nge-immunotherapy, ikakhulukazi i-checkpoint inhibitors (ipilimumab, nivolumab, ne-pembrolizumab), odokotela babona izinkinga eziyingqayizivele ezingase ziphakame ngenxa yokuthatha lezi zidakamizwa ezintsha.
Sibutsetelo se-Checkpoint Inhibitors
Ukuze uqonde imiphumela emibi noma izidakamizwa ze- checkpoint inhibitors , kubalulekile ukuqonda ukuthi lolu hlobo lwe-immunotherapy lusebenza kanjani.
Ngamafuphi, ukuhlolwa kwamagciwane okuvame ukulwa namasosha omzimba (okubizwa ngokuthi ama-T cells). Lezi zinhlayiya ze-checkpoint zisebenza ngendlela eyinkimbinkimbi yokumisa ukuvimbela ama-T cells omuntu ekuhlaseleni amangqamuzana aphilile-amasonto angaphandle kuphela (isibonelo, amangqamuzana aphethwe igciwane).
Ngeshwa, amangqamuzana omdlavuza akhohlisayo ngokuthi enza futhi aveze amakhemikhali awo okuhlola, yingakho umzimba wakho ungahlaseli isifo esibi, njengoba ubungacabanga.
Kodwa-ke, ososayensi baye balwa ngokudala izindlela zokwelapha ezivimbela lezi zindawo zokuhlola ezitholakala emangqamuzaneni omdlavuza ngamathemba ukuthi isimiso somzimba sokuzivikela somzimba manje singayibona umdlavuza njengangaphandle, siqalise ukuhlaselwa, futhi siyicacise.
Izinyopho ze-Checkpoint Inhibitors
Yiqiniso, izinkinga zingase ziphakame uma amasosha omzimba omuntu eqala ukudideka futhi eqala ukuhlasela amaseli avamile, enempilo ngaphezu kwamangqamuzana omdlavuza ombi.
Ngamanye amazwi, ukuvuvukala okukhulu, ukulimala komzimba, nezifo ezizimele kungenziwa ngokusetshenziswa kwalezi zinambuzane zokuhlola.
Eqinisweni, ucwaningo lubonisa ukuthi lezi zingozi, ezibizwa ngokuthi izenzakalo ezimbi ezihlobene nomzimba, zivela kubantu abangamaphesenti angama-85 emva kokwelashwa ne-inhibitor ipilimumab yokuhlola. Zenzeka ngamaphesenti angaba ngu-70 abantu ngemuva kokwelashwa nge-checkpoint inhibitors nivolumab noma i-pembrolizumab.
Njengengxenye, i-ipilimumab ivimbela ukuhlolwa kwamagciwane okuyi-CTLA-4 (iprotheni ehambisana ne-cytotoxic T- lymphocyte 4) futhi isetshenziselwe ukwelapha i- melanoma .
I-Nivolumab kanye ne-pembrolizumab target PD-1 (i-programmed death receptor-1) futhi isetshenziselwe ukwelapha umdlavuza we-cancer njenge-melanoma, umdlavuza we-renal cell, umdlavuza ongasona omncane wesifo samaphaphu, kanye ne-Hodgkin's lymphoma.
Ukubuyela emuva ezinotshweni, noma kunjalo, izinhlelo ezibhekiswe kuzo eziyinhloko ukuthi lezi zivivinyo zokuhlola "ngokungalungile" emzimbeni kukhona isikhumba, isisu somzimba, isibindi, nezinhlelo ze-endocrine.
I-Skin Toxicities
Izinkinga zesikhumba yisenzakalo esivame kakhulu esihlobene nesigciwane sokuzivikela esihlobene nokuthatha i-checkhibit inhibitor, futhi bavame ukuqala kokuqala ekwelapheni.
Izibonelo zezinkinga zesikhumba zihlanganisa ukuqubuka, ukuhlakulela, i-alopecia (ukulahleka kwezinwele), kanye ne- vitiligo .
Izinkinga zomlomo zinjengomlomo owomile kanye nomlomo we-mucositis (uma izilonda zenza emlonyeni) zingase zenzeke.
Ukwelashwa kwe-rash ngokuvamile kuhlanganisa ukusebenzisa ukhilimu we-corticosteroid. Nakuba ngabe ukuqubuka kunzima, i-corticosteroid yomlomo ngezinye izikhathi idinga. Ukuthatha i-antihistamine yomlomo njengoBenadryl (diphenhydramine) ingasiza ekubambeni.
Ngokuvamile, uma ukuqhuma kunzima, okusho ukuthi kuhlanganisa ngaphezu kwamaphesenti angama-30 omzimba, umuntu cishe uzodinga i-steroids enikezwa nge-vein (intravenously) elandelwa umthamo we-oral steroids.
Kubalulekile ukuthi uqaphele ukuthi izidakamizwa ezinzima ezifana ne- Stevens-Johnson syndrome ziye zavame ukubikwa kubantu abaphatha i-inhibitor yokuhlola.
Yingakho wena noma udokotela wakho womdlavuza othandekayo uzoqapha ngokucophelela ngenkathi ethatha i-immunotherapy futhi ngokushesha ubona i- dermatologist uma i-rash yakho ibukeka ibuhlungu (njengokungathi yenza ama-blisters) noma uma ungatholi usizo ngezinyathelo ezilula njengekhilimu ye-corticosteroid.
Izinyathelo Zokuqeda Amathumbu Emathunjini
Isifo sohudo kanye ne-colitis, okubangela ubuhlungu besisu nangesinye isikhathi igazi e-stool, kukhona izinkinga ezimbili zamathumbu ezingase zenzeke ngenxa yokuthatha inhibitor yokuhlola. Uma lezi zenzeke zenzeka, zibonisa ngokujwayelekile amasonto ayisithupha noma kamuva ngemuva kokuqala i-immunotherapy.
Lokho kusho ukuthi lezi zimo ezimbi zibonakala zivame kakhulu kulabo abathola ama-antibodies okuvimbela i-CTLA-4 (isibonelo, ipilimumab ye-melanoma ephakeme), uma kuqhathaniswa nalabo abathola ama-inhibitors e-PD-1 (isibonelo, i-nivolumab ye-cell squamous esedlule engeyona encane umdlavuza wesifo samaphaphu).
Ukwelashwa kwesifo sohudo esiphuthumayo kanye nokuqala kuhlanganisa ukudla okunamanzi okudliwayo, ukudla okunomdlavuza , futhi mhlawumbe imithi yokulwa nesifo sohudo njengo-Imodium (loperamide). Kodwa uma isifo sohudo siqhubeka isikhathi esingaphezu kwezinsuku ezimbili noma ezintathu, naphezu kwalezi zindlela ezilula, noma uma isifo sohudo sinzima kakhulu (ukunyakaza okuyisine noma ngaphezulu kwamathumbu ngosuku ngalokhu kuvamile), ukuhlolwa okuphelele kuzokwenziwa ukuze kuhlolwe ukuhlolwa kwesifo sohudo ukutheleleka kuyisifo, hhayi umuthi.
Uma ukutheleleka kuphelelwe yisikhathi, futhi imbangela ibhekwa njengokwelashwa-okuhlobene, i-corticosteroids iyadingeka futhi ngezinye izikhathi imishanguzo enamandla kakhulu evikela isimiso somzimba sokuzivikela njenge- Remicade (infliximab) iyadingeka.
Enye yezinto ezisongela ukuphila, nakuba kungavamile, izinkinga zokuguliswa yizinyanga lapho odokotela abaqaphele khona yi- perforation emathunjini emathunjini (lapho umgodi uhlotshaniswa nodonga lwamathumbu kusukela ekuvuvukala okukhulu).
Ukuqothuka kwesibindi
I-inhibitors yokuhlola ingaholela ekukhuleni kwamabhomu enzyme, okuyisibindi sokuvuvukala kwesibindi. Lezi ziphakamiso ngokuvamile zibonwa ezinyangeni ezimbili kuya kwezintathu ngemuva kokuqala ukwelapha.
Ngokuvamile, udokotela uzoqapha ukuhlolwa kwegazi lesibindi , ikakhulukazi ngaphambi kokuhlolwa komzimba ngamunye, futhi uma izinyimba zanda, kuzomiswa umsebenzi ukuze kutholakale ukuthi imbangela ihambisana nokuzivikela noma enye into (isibonelo, enye imithi noma ukutheleleka ngegciwane).
Njengeminye imiphumela emibi ehlobene nomzimba, uma imbangela inqunywa ukuthi ihlotshaniswe ne-immunotherapy, i-corticosteroids izobe ishiwo. Uma isifo sobindi sinzima kakhulu, ukwelashwa nge-immunotherapy kungadingeka ukuthi kumiswe ngokuphelele.
I-Endocrine System Toxicities
Izenzakalo ezimbi ezihlobene nomzimba zingase zenzeke ngaphakathi kwesimiso se-endocrine somzimba, esihlanganisa igwebu le-pituitary, ugundane we-thyroid kanye nama-gland adrenal. Ngokwesilinganiso, izimpawu zivela cishe ngemva kwamasonto ayisishiyagalolunye emva kokuqala ukwelashwa futhi zingabandakanya:
- Ukukhathala
- Ukungabi namandla
- I-nausea
- Ukudideka
- Izinwele
- Ukulahlekelwa kwesifiso
- Izinkinga zembono
- Fever
Esinye sezimo ezimbi kakhulu ze-endocrine yimiphumela ye- hypothyroidism , okuyilapho umuntu eqala i-thyroid engasebenzi.
I-gland ye-thyroid engasebenzi kakhulu, ebizwa nge-hyperthyroidism, nayo ibike. Zombili lezi zimo zingaphathwa yi-endocrinologist futhi zitholwe ngokusebenzisa ukuhlolwa kwegazi, ikakhulukazi ukuhlolwa kwegazi okwakhiqiza i-hormone (TSH). I-Hypothyroidism idinga ukwelashwa nge-hormone ye-thyroid, ebizwa nge-Synthroid (levothyroxine).
Ngaphezu kwe-hypothyroidism, enye inkinga ejwayelekile ye-endocrine engase ikhule ngenxa yokuthatha uphawu lokuvimbela i-immunotherapy yi-hypophysitis, okuwukuvuvukala kwe-pituitary gland-okubizwa ngokuthi i-master gland ngoba ikhishwa ama-hormone amaningi emzimbeni.
Ukuphefumula kungabangela ukukhathala nokuhlolelwa ikhanda nokuhlolwa kwegazi kwembula amaningana ama-hormone aphansi. Ukucubungula ukuhlolwa kungabonisa nokuvuvukala kwegciwane le-pituitary. Uma kutholakala maduzane, i-high-dose corticosteroids inganciphisa ukuvuvukala phansi ngokwanele ukuvimbela isidingo sezidakamizwa zesikhathi eside sokusebenzisa izidakamizwa.
Uma izigulane eziyingozi ziyathinteka, umuntu angase athuthukise ukucindezeleka kwegazi eliphansi, ukuphelelwa amandla kwamanzi kanye nezinkinga ze-electrolyte ezinamazinga aphezulu e-potassium namazinga aphansi e-sodium egazini. Lokhu kuyiphuthumayo kwezokwelapha futhi kudinga ukuthi umuntu angene esibhedlela futhi athole i-corticosteroids.
Okokugcina, uhlobo lwesifo sikashukela sohlobo olusha olusha olungajwayelekile aluxhunywanga ngokuthatha i-PD-1 inhibitor. Yingakho odokotela bavame ukuhlola i-glucose (ushukela emazingeni akho egazi) lapho uqala ukwelashwa.
Izinsalela ezidakayo
I-immunotherapy nayo ingabangela ukuvuvukala emaphashini, futhi lokhu kubizwa nge-pneumonitis, nakuba kungavamile, uma kuqhathaniswa nezidakamizwa ezibalulwe ngenhla. Lo mphumela omubi ukhathazeka kakhulu kubantu abanomdlavuza wamapapu ophuthumayo owela i-immunotherapy, njengoba umsebenzi wabo wamaphaphu usuvele ukhubazekile emdlalweni. Kungabangela izimpawu ezifana nokukhwehlela noma ubunzima bokuphefumula.
Ngenkathi ngokuvamile kuyingozi engavamile, i-pneumonitis ingasongela ukuphila. Uma usolwa, udokotela wakho uzolawula ezinye izimbangela zokuvuvukala kwamaphaphu njengengculaza (okuthiwa i-pneumonia) noma ukuqhubeka komdlavuza. Udokotela uzovame ukuhlehlisa i-CT scan yesifuba sokusiza ekuxilongweni.
Ukwelapha kuvame ukufaka ukuyeka i-immunotherapy isikhathi esinqunyiwe ngenkathi umuntu ehlola ngokucophelela amaphaphu abo. Ama-corticosteroids nawo avame ukunikezwa, futhi ezimweni ezinzima, i-immunosuppressant efana ne-Remicade (infliximab) ingadingeka uma umuntu engaphumeleli nge-steroids.
Okokugcina, ezinye izimo ezingavamile ezihlobene nomzimba omzimba zibikwe njengezinkinga zesisindo noma zeso. Kulesi sibonelo, udokotela wakho uzokutshela ochwepheshe, i- neurologist noma i- ophthalmologist , ukuze uthole isifo esifanele sokuxilongwa kanye nokwelapha.
Izwi elivela
Uma wena noma othandekayo uthatha i-inhibitor yokuhlola, kuhle ukwazi ngolwazi olunobuthi obuhlobene nalo, ngoba luhlukile kulabo abahlotshaniswa ne-chemotherapies yendabuko.
Ngamanye amazwi, izimpawu ezifihlakeleyo nemiphumela yalezi zimbi ezimbi ziyinto enomlando kumadokotela odlavuza. Noma kunjalo, ungesabi nguwo. Kunalokho, fundiswa futhi uqaphele, njengoba abaningi bazoxazulula uma beqashelwa ngokushesha.
> Imithombo:
> Kroschinsky F et al. Izidakamizwa ezintsha, izidakamizwa ezintsha: imiphumela emibi yezinhlobonhlobo zamanje nomkhankaso we-cancer kanye nabaphathi babo. Ukunakekelwa kweCrit. 2017; 21: 89.
> Linardou H, Gogas H. Ukuphathwa kokudakayo kwe-immunotherapy yeziguli ezine-melanoma ye-metastatic. Ann Transl Med . 2016 Jul; 4 (14): 272.
> Michot JM et al. Izenzakalo ezimbi ezihlobene nomzimba nge-immune checkpoint blockade: ukubuyekezwa okuphelele. I-Eur J Cancer . 2016 Feb; 54: 139-48.
> Iphosta M, iWolchok J. Toxicities ehambisana ne-checkpoint inhibitor immunotherapy. Ku: UpToDate, Atkins MB (Ed), UpToDate, Waltham, MA.
> I-Villadolid J, i-Amin A. I-immune checkpoint inhibitors emisebenzini yomtholampilo: ubuyekeze ekulawuleni izidakamizwa ezihlobene nomzimba. Ukuhumusha i-Cancer Cancer Res . 2015 Okthoba; 4 (5): 560-75.