Izinhlobo / i-prostate / i-prostate-hormone-therapy-fact-sheet
Okuqukethwe
- 1 Ukwelashwa Kwehormone Komdlavuza We-Prostate
- 1.1 Yini ama-hormone ocansi abesilisa?
- 1.2 Ngabe ama-hormone akuvuselela kanjani ukukhula komdlavuza wendlala yesinye?
- 1.3 Yiziphi izinhlobo zokwelashwa kwamahomoni ezisetshenziselwa umdlavuza wendlala yabesilisa?
- 1.4 Ukwelashwa kwehomoni kusetshenziswa kanjani ekwelapheni umdlavuza wendlala yabesilisa?
Ukwelashwa Kwehormone Komdlavuza We-Prostate
Yini ama-hormone ocansi abesilisa?
AmaHormone yizinto ezenziwe yizindlala emzimbeni ezisebenza njengezimpawu zamakhemikhali. Zithinta izenzo zamaseli nezicubu ezindaweni ezahlukahlukene emzimbeni, zivame ukufinyelela izinhloso zazo ngokuhamba egazini.
Ama-Androgens (ama-hormone abesilisa besilisa) ayisigaba samahomoni alawula ukuthuthukiswa kanye nokugcinwa kwezimpawu zesilisa. I-Testosterone ne-dihydrotestosterone (DHT) yi-androgens eningi kakhulu emadodeni. Cishe yonke i-testosterone ikhiqizwa emasendeni; inani elincane likhiqizwa yizindlala ze-adrenal. Ngaphezu kwalokho, amanye amangqamuzana omdlavuza wendlala yesinye athola ikhono lokwenza i-testosterone kusuka ku-cholesterol (1).
Ngabe ama-hormone akuvuselela kanjani ukukhula komdlavuza wendlala yesinye?
Ama-Androgens ayadingeka ekukhuleni okujwayelekile nokusebenza kwe-prostate, indlala ohlelweni lokuzala lwabesilisa olusiza ukwenza isidoda. I-Androgens nayo iyadingeka ukuze umdlavuza we-prostate ukhule. Ama-Androgens akhuthaza ukukhula kwawo womabili amaseli wendlala ejwayelekile futhi anomdlavuza ngokubopha nokwenza kusebenze i-androgen receptor, iphrotheni evezwa kumaseli wendlala (2). Uma seyenziwe yasebenza, i-receptor ye-androgen ivuselela ukubonakaliswa kofuzo oluthile obangela ukuthi amaseli e-prostate akhule (3).
Ekuqaleni kokukhula kwabo, umdlavuza we-prostate udinga amazinga aphakeme kakhulu ama-androgens ukuze akhule. Umdlavuza onjalo wendlala yesinye ubizwa ngokuthi yi-castration sensitive, i-androgen incike, noma i-androgen iyazwela ngoba izindlela zokwelapha ezinciphisa amazinga e-androgen noma ezivimba umsebenzi we-androgen zingavimbela ukukhula kwazo.
Umdlavuza wendlala yelashwa ngezidakamizwa noma ngokuhlinzwa okuvimba i-androgens ekugcineni kube ukumelana nokuthena (noma i-castrate), okusho ukuthi ingaqhubeka nokukhula noma amazinga e-androgen emzimbeni ephansi kakhulu noma engatholakali. Esikhathini esedlule lezi zicubu zazibizwa nangokuthi i-hormone resistant, i-androgen ezimele, noma i-hormone refractory; kodwa-ke, lawa magama akuvamile ukuthi asetshenziswe manje ngoba izicubu esezimelane nokuthenwa zingaphendula kumuthi omusha noma ngaphezulu we-antiandrogen.
Yiziphi izinhlobo zokwelashwa kwamahomoni ezisetshenziselwa umdlavuza wendlala yabesilisa?
Ukwelashwa kwehormone komdlavuza wendlala yesinye kungavimba ukukhiqizwa noma ukusetshenziswa kwama-androgens (4). Okwamanje ukwelashwa okutholakalayo kungenza ngezindlela eziningana:
- Ukunciphisa ukukhiqizwa kwe-androgen ngamasende
- Ukuvimba isenzo se-androgens kuwo wonke umzimba
- Vimba ukukhiqizwa kwe-androgen (synthesis) emzimbeni wonke
Ukwelashwa okunciphisa ukukhiqizwa kwe-androgen ngamasende kuyizindlela zokwelashwa ze-hormone ezisetshenziswa kakhulu zomdlavuza wesinye kanye nohlobo lokuqala lokwelashwa kwamahomoni olutholwa ngabesilisa abaningi abanomdlavuza wendlala yesinye. Leli fomu lokwelashwa kwehomoni (elibizwa nangokuthi ukwelashwa kwe-androgen, noma i-ADT) lifaka:
- I-Orchiectomy, inqubo yokuhlinza ukususa elilodwa noma womabili amasende. Ukususwa kwamasende kunganciphisa izinga le-testosterone egazini ngo-90 kuye ku-95% (5). Lolu hlobo lwezokwelapha, olubizwa ngokuthi ukuthenwa ngokuhlinzwa, luhlala unomphela futhi alunakulungiswa. Uhlobo lwe-orchiectomy olubizwa nge-subcapsular orchiectomy lususa kuphela izicubu ezisemasendeni ezikhiqiza i-androgens, hhayi lonke isende.
- Izidakamizwa ezibizwa ngokuthi yi-luteinizing hormone-releasing hormone (LHRH) agonists, evimbela uketshezi kwehomoni ebizwa nge-luteinizing hormone. Ama-agonist e-LHRH, kwesinye isikhathi abizwa ngokuthi ama-LHRH analogs, angamaprotheni okwenziwa afana nse ne-LHRH futhi abophezela kumamukeli we-LHRH endlaleni ye-pituitary. (I-LHRH yaziwa nangokuthi i-gonadotropin-ikhipha i-hormone noma i-GnRH, ngakho-ke ama-agonists e-LHRH abizwa nangokuthi yi-GnRH agonists.)
Imvamisa, lapho amazinga e-androgen emzimbeni esezingeni eliphansi, i-LHRH ivuselela indlala ye-pituitary ukuthi ikhiqize i-luteinizing hormone, yona evuselela amasende ukuthi akhiqize i-androgens. Ama-agonists e-LHRH, njenge-LHRH yomzimba uqobo, aqale akhuthaze ukukhiqizwa kwehomoni ye-luteinizing. Kodwa-ke, ukutholakala okuqhubekayo kwamazinga aphakeme ama-agonist e-LHRH empeleni kudala ukuthi le ndlala ye-pituitary iyeke ukukhiqiza i-hormone ye-luteinizing, futhi ngenxa yalokho amasende awakhuthazwa ukukhiqiza i-androgens.
Ukwelashwa nge-agonist ye-LHRH kubizwa ngokuthi yi-medical castration noma i-chemical castration ngoba isebenzisa izidakamizwa ukufeza into efanayo nokuhlinzwa (i-orchiechtomy). Kepha, ngokungafani ne-orchiectomy, imiphumela yale mithi ekukhiqizeni i-androgen iyabuyiselwa. Lapho ukwelashwa kumisiwe, ukukhiqizwa kwe-androgen kuvame ukuqala kabusha.
Ama-agonist e-LHRH anikezwa ngomjovo noma afakwa ngaphansi kwesikhumba. Ama-agonist amane e-LHRH avunyelwe ukwelapha umdlavuza wendlala yabesilisa e-United States: i-leuprolide, i-goserelin, i-triptorelin ne-histrelin.
Lapho iziguli zithola i-agonist ye-LHRH okokuqala ngqa, zingathola into ebizwa nge- "testosterone flare." Lokhu kwanda kwesikhashana kwezinga le-testosterone kwenzeka ngoba ama-agonists e-LHRH kafushane abangela ukuthi indlala yebhinqa ikhiphe i-hormone eyengeziwe ye-luteinizing ngaphambi kokuvimba ukukhishwa kwayo. Ukuqhuma kungazenza zibe zimbi izimpawu zomtholampilo (ngokwesibonelo, ubuhlungu bamathambo, ukuvinjelwa kwe-ureter noma ukuphuma kwesinye, nokucindezelwa kwentambo yomgogodla), okungaba inkinga ethile emadodeni anomdlavuza we-Prostate. Ukwanda kwe-testosterone kuvame ukubalwa ngokunikeza olunye uhlobo lokwelashwa kwamahomoni olubizwa ngokuthi yi-antiandrogen therapy kanye ne-agonist ye-LHRH emasontweni ambalwa okuqala okwelashwa.
- Izidakamizwa ezibizwa ngokuthi yi-LHRH antagonists, okungenye indlela yokuthumela kwezokwelapha. Abaphikisi be-LHRH (ababizwa nangokuthi abamelene ne-GnRH) bavimbela i-LHRH ekuzibophezeleni kuma-receptors ayo endlala ye-pituitary. Lokhu kuvimbela uketshezi kwe-luteinizing hormone, emisa amasende ekukhiqizeni i-androgens. Ngokungafani nama-agonists e-LHRH, abaphikisi be-LHRH ababangeli ukuqhuma kwe-testosterone.
Umuntu oyedwa olwa ne-LHRH, u-degarelix, njengamanje uvunyelwe ukwelapha umdlavuza we-Prostate e-United States. Inikezwa ngomjovo.
- Ama-Estrogens (ama-hormone akhuthaza izici zobulili besifazane). Yize ama-estrogens nawo ekwazi ukuvimbela ukukhiqizwa kwe-androgen ngamasende, awavamile ukusetshenziswa namuhla ekwelapheni umdlavuza wendlala yesinye ngenxa yemiphumela yawo emibi.
Ukwelashwa okuvimba isenzo se-androgens emzimbeni (obizwa nangokuthi izindlela zokwelapha ze-antiandrogen) kuvame ukusetshenziswa lapho i-ADT iyeka ukusebenza. Ukwelashwa okunjalo kufaka:
- Ama-Androgen receptor blockers (abizwa nangokuthi abaphikisi be-androgen receptor antagonists), okuyizidakamizwa ezincintisana nama-androgens okubopha kumamukeli we-androgen. Ngokuqhudelana ngokubopha kumamukeli we-androgen, lezi zindlela zokwelapha zinciphisa ikhono lama-androgens ukukhuthaza ukukhula komdlavuza wesinye.
Ngoba i-androgen receptor blocker ayikuvimbi ukukhiqizwa kwe-androgen, kuyaqabukela zisetshenziswe zodwa ukwelapha umdlavuza wesinye. Esikhundleni salokho, zisetshenziswa ngokuhlangana ne-ADT (kungaba i-orchiectomy noma i-agonist ye-LHRH). Ukusetshenziswa kwe-androgen receptor blocker kuhlanganiswe ne-orchiectomy noma i-agonist ye-LHRH ibizwa ngokuthi yi-androgen blockade ehlanganisiwe, ukuvinjelwa okuphelele kwe-androgen, noma ukuvinjelwa okuphelele kwe-androgen.
Ama-Androgen receptor blockers avunyelwe e-United States ukwelapha umdlavuza wendlala yabesilisa ahlanganisa i-flutamide, i-enzalutamide, i-apalutamide, i-bicalutamide, ne-nilutamide. Anikezwa njengamaphilisi okufanele agwinywe.
Ukwelashwa okuvimba ukukhiqizwa kwama-androgens emzimbeni wonke kufaka:
- I-Androgen synthesis inhibitors, okuyizidakamizwa ezivimbela ukukhiqizwa kwama-androgens yizindlala ze-adrenal namaseli womdlavuza wendlala yesinye uqobo, kanye nangamasende. Noma ukusikwa kwezokwelapha noma kokuhlinzwa akuvimbeli izindlala nezindlala zomdlavuza wendlala ekukhiqizeni i-androgens. Noma amanani we-androgens lawa maseli akhiqizwa emancane, anganela ukuxhasa ukukhula kwamanye umdlavuza we-prostate.
I-Androgen synthesis inhibitors ingehlisa amazinga e-testosterone emzimbeni womuntu ngezinga elikhulu kunanoma ikuphi okunye ukwelashwa okwaziwayo. Le mithi ivimba ukukhiqizwa kwe-testosterone ngokuvimbela i-enzyme ebizwa nge-CYP17. Le enzyme, etholakala kwizicubu zesende, i-adrenal, ne-prostate tumor, iyadingeka emzimbeni ukukhiqiza i-testosterone kusuka ku-cholesterol.
Ama-inhibitor amathathu we-androgen synthesis avunyelwe e-United States: i-abiraterone acetate, ketoconazole, ne-aminoglutethimide. Zonke zinikezwa njengamaphilisi okufanele zigwinywe.
I-Abiraterone acetate ivunyelwe ngokuhlangana ne-prednisone ukwelapha umdlavuza wendlala yesifo sofuba obucayi obusengozini enkulu kanye nomdlavuza wesibeletho ongazweli ekuthumeni. Ngaphambi kokuvunyelwa kwe-abiraterone ne-enzalutamide, imithi emibili evunyelwe izinkomba ngaphandle komdlavuza wendlala yesinye — i-ketoconazole ne-aminoglutethimide — kwesinye isikhathi yayisetshenziswa njengelebuli njengolayini bomugqa wesibili womdlavuza wendlala yesinye.
Ukwelashwa kwehomoni kusetshenziswa kanjani ekwelapheni umdlavuza wendlala yabesilisa?
Ukwelashwa kweHormone kungasetshenziswa ngezindlela eziningana ukwelapha umdlavuza wesinye, kufaka phakathi:
Umdlavuza wesibeletho osezingeni lokuqala onobungozi obuphakathi noma obukhulu bokuphindeka. Amadoda anomdlavuza wendlala yesigaba sokuqala onobungozi obuphakathi noma obuphakeme bokuphinda avame ukuthola ukwelashwa kwe-hormone ngaphambi, phakathi, kanye / noma ngemuva kokwelashwa ngemisebe, noma angathola ukwelashwa kwe-hormone ngemuva kwe-prostatectomy (ukuhlinzwa ukuze kususwe indlala yesinye) (6) . Izici ezisetshenziselwa ukunquma ubungozi bokuphindeka komdlavuza wesibeletho zifaka phakathi ibanga lesimila (njengoba kulinganiswa isilinganiso seGleason), izinga lapho isimila sesisabalale laba yizicubu ezizungezile, nokuthi amaseli wesimila atholakala yini kuma-lymph node aseduzane ngesikhathi sokuhlinzwa.
Ubude bokwelashwa nge-hormone therapy yomdlavuza wendlala yesigaba sokuqala kuncike engozini yendoda yokuphindeka. Kwabesilisa abanomdlavuza ophakathi nendawo onobungozi, ukwelashwa kwamahomoni ngokuvamile kunikezwa izinyanga eziyisithupha; kubantu besilisa abanezifo ezinobungozi obukhulu unikezwa izinyanga eziyi-18-24.
Abesilisa abanokwelashwa kwe-hormone ngemuva kwe-prostatectomy baphila isikhathi eside ngaphandle kokuphindaphinda kunamadoda ane-prostatectomy eyedwa, kepha awaphili isikhathi eside (6). Abesilisa abathola ukwelashwa ngama-hormone ngemuva kokwelapha ngemisebe kwangaphandle kwemishanguzo yomdlavuza wesinye noma ophakathi nobungozi obukhulu baphila isikhathi eside, kokubili ngokuphelele nangaphandle kokuphindeka, kunamadoda alashwa ngemithi yokwelashwa ngemisebe yodwa (6, 7). Abesilisa abathola ukwelashwa kwamahomoni ngokuhambisana nokwelashwa ngemisebe baphila isikhathi eside kunamadoda athola ukwelashwa ngemisebe eyedwa (8). Kodwa-ke, isikhathi esifanele nobude be-ADT, ngaphambi nangemva kokwelashwa ngemisebe, akukasungulwa (9, 10).
Ukusetshenziswa kokwelapha i-hormone (kukodwa noma kuhlanganiswe ne-chemotherapy) ngaphambi kokuthi i-prostatectomy ingakhonjiswa ukwelula isikhathi sokuphila futhi akuyona indlela ejwayelekile yokwelashwa. Ukuvinjelwa okukhulu kwe-androgen ngaphambi kwe-prostatectomy kufundwa kuzilingo zomtholampilo.
Umdlavuza wesibeletho obuyile / ophindaphindiwe Ukwelashwa kweHormone okusetshenziswe yedwa ukwelashwa okujwayelekile kwabesilisa abanomdlavuza we-prostate ophindaphindiwe njengoba kubhalwe yi-CT, i-MRI, noma ukuskena kwamathambo ngemuva kokwelashwa nge-radiation therapy noma i-prostatectomy. ukwelashwa kwesinye isikhathi kunconywa amadoda aphindaphindiwe "ngamakhemikhali" - ukukhuphuka kwezinga le-prostate-specific antigen (PSA) kulandela ukwelashwa okuyisisekelo kwendawo ngokuhlinzwa noma ngemisebe — ikakhulukazi uma izinga le-PSA liphindeka kabili ezinyangeni ezingaphansi kwezintathu kanti umdlavuza awukaze ukubhebhetheka.
Isivivinyo somtholampilo esingahleliwe phakathi kwamadoda aphindaphindiwe ngamakhemikhali ngemuva kwe-prostatectomy athola ukuthi abesilisa ababenokwelashwa kwe-antiandrogen kanye nokwelashwa ngemisebe babengenamathuba amancane okuthuthukisa imastastase noma babulawe ngumdlavuza wendlala noma jikelele kunabesilisa ababene-placebo plus radiation (11). Kodwa-ke, iziguli ezinamanani aphansi e-PSA azange zibonakale zizuza ngokwengezwa kokwelapha i-hormone kwimisebe. Olunye uvivinyo lwakamuva lomtholampilo lukhombisile ukuthi kwabesilisa abanamazinga akhuphukayo e-PSA ngemuva kokwelashwa okuyisisekelo okuyibo ababesengozini enkulu ye-metastasis kepha babengenabo ubufakazi besifo se-metastatic, ukungeza i-chemotherapy nge-docetaxel ku-ADT kwakungaphakeme kune-ADT ngokwezinyathelo ezimbalwa zokusinda ( 12).
Umdlavuza we-Prostate noma we-metastatic Ukwelashwa kweHormone okusetshenziswa kuphela ukwelashwa okujwayelekile kwabesilisa okutholakala ukuthi banesifo se-metastatic (okungukuthi, isifo esisakazekele kwezinye izingxenye zomzimba) lapho umdlavuza wabo wendlala yesinye utholakala okokuqala (13). Ukuhlolwa komtholampilo kukhombisile ukuthi amadoda anjalo asinda isikhathi eside lapho elashwa nge-ADT kanye ne-abiraterone / prednisone, enzalutamide, noma i-apalutamide kunalapho elashwa nge-ADT kuphela (14-17). Kodwa-ke, ngoba ukwelashwa kwamahomoni kungaba nemiphumela emibi kakhulu, amanye amadoda akhetha ukungayithathi imishanguzo yehomoni kuze kube yilapho kuvela izimpawu.
Imiphumela yokuqala yesivivinyo esixhaswe yi-NCI esasenziwa amaqembu amabili abambisene nomdlavuza-i-Eastern Cooperative Oncology Group (ECOG) kanye ne-American College of Radiology Imaging Network (ACRIN) -sikisele ukuthi amadoda anomdlavuza we-prostate ozwela i-hormone othola i-hormone i-chemotherapy drug docetaxel ekuqaleni kwelashwa ejwayelekile ye-hormone iphila isikhathi eside kunamadoda athola ukwelashwa kwamahomoni eyedwa. Abesilisa abanesifo se-metastatic esibanzi kakhulu babonakala bezuza kakhulu ekungezweni kwasekuqaleni kwe-docetaxel. Lokhu okutholakele kusanda kuqinisekiswa ngokulandelwa okude (18).
Ukudonswa kwezimpawu. Ukwelashwa kweHormone kwesinye isikhathi kusetshenziselwa wedwa ukucubungula noma ukuvimbela izimpawu zasendaweni emadodeni anomdlavuza we-Prostate wendawo ongakhethelwa ukuhlinzwa noma ukwelashwa ngemisebe (19). Amadoda anjalo afaka phakathi labo abanesilinganiso seminyaka yokuphila, labo abanezimila ezisezingeni eliphakeme, kanye / noma labo abanezinye izimo zezempilo ezinzima.
Nika amandla ukuvuselelwa okuzenzakalelayo kwamazwana