Iindidi / iprostate / i-prostate-hormone-therapy-sheet-sheet
Iziqulatho
Unyango lweHormone lweCancer Prostate
Yintoni iihomoni zesini samadoda?
IiHormone zizinto ezenziwe ngamadlala emzimbeni asebenza njengeempawu zemichiza. Zichaphazela iintshukumo zeeseli kunye nezicubu kwiindawo ezahlukeneyo emzimbeni, zihlala zifikelela kwiithagethi zazo ngokuhamba ngegazi.
I-Androgens (iihomoni zesini esingamadoda) yiklasi lamahomoni alawula ukukhula kunye nokugcinwa kweempawu zamadoda. I-testosterone kunye ne-dihydrotestosterone (DHT) zezona androgens zininzi emadodeni. Phantse yonke i-testosterone iveliswa kumatyhalarha; isixa esincinci siveliswa ngamadlala adrenal. Ukongeza, ezinye iiseli zomhlaza wendlala zifumana amandla okwenza testosterone kwi-cholesterol (1).
Ihormone ikukhuthaza njani ukukhula komhlaza wedlala lobudoda?
I-Androgens ziyafuneka ekukhuleni kwesiqhelo kunye nokusebenza kweprotrate, idlala kwinkqubo yokuzala eyindoda enceda ukwenza isidoda. I-Androgens ikwanyanzeleka ukuba ukukhula komhlaza wedlala lendlala. I-Androgens ikhuthaza ukukhula kokubini kwesiqhelo kunye nomhlaza iiseli zeprotate ngokuzibophelela kunye nokwenza ukuba i-androgen receptor, iprotein ebonakaliswe kwiiseli zeprotate (2). Nje ukuba isebenze, i-androgen receptor ivuselela ukubonakaliswa kohlobo oluthile olubangela ukuba iiseli zeprostate zikhule (3).
Kwasekuqaleni kokukhula kwabo, iicancer ze-Prostate zifuna amanqanaba aphezulu e-androgens ukuze zikhule. Umhlaza weprostate ubizwa ngokuba yi-castration sensitive, i-androgen exhomekeke kuyo, okanye i-androgen ethe-ethe kuba unyango olwehlisa amanqanaba e-androgen okanye ibhloko ye-androgen inokuthintela ukukhula kwabo.
Umhlaza wesifo se-Prostate uphathwe ngamachiza okanye utyando oluthintela i-androgens ekugqibeleni ibe yi-castrate (okanye i-castrate) enganyangekiyo, oko kuthetha ukuba banokuqhubeka nokukhula nokuba amanqanaba e-androgen asezantsi kakhulu okanye awabonakali. Kwixesha elidlulileyo ezi tumors zazibizwa ngokuba kukumelana nehomoni, i-androgen ezimeleyo, okanye i-hormone refractory; Nangona kunjalo, la magama kunqabile ukuba asetyenziswe ngoku kuba amathumba anganyangekiyo ekuthumeni anokuphendula kwelinye okanye nangaphezulu amachiza e-antiandrogen amatsha.
Zeziphi iintlobo zonyango lwehomoni ezisetyenziselwa umhlaza wedlala lobudoda?
Unyango lweHormone lomhlaza wedlala lesinyi lunokuthintela imveliso okanye ukusetyenziswa kwe-androgens (4). Okwangoku unyango olwenziweyo lunokwenza ngeendlela ngeendlela:
- Ukunciphisa imveliso ye-androgen ngamasende
- Ukuthintela isenzo se-androgens kuwo wonke umzimba
- Vimba imveliso ye-androgen (synthesis) kuwo wonke umzimba
Unyango olucutha ukuveliswa kwe-androgen ngamatyhalarha zezona zisetyenziswa kakhulu kunyango lwehomoni yomhlaza wedlala lobudoda kunye nohlobo lokuqala lonyango lwehomoni olufunyanwa uninzi lwamadoda anomhlaza wesibeletho. Olu hlobo lonyango lwehomoni (ekwabizwa ngokuba lonyango lwe-androgen, okanye i-ADT) ibandakanya:
- I-Orchiectomy, inkqubo yotyando lokususa elinye okanye omabini amasende. Ukususwa kwamasende kungalinciphisa inqanaba le testosterone egazini ngama-90 ukuya kuma-95% (5). Olu hlobo lonyango, olubizwa ngokuba lutyando, lusisigxina kwaye alunakulungiseka. Uhlobo lwe-orchiectomy olubizwa ngokuba yi-subcapsular orchiectomy lususa kuphela izihlunu ezikumatyhalarha avelisa i-androgens, endaweni yalo lonke ityhalarha.
- Iziyobisi ezibizwa ngokuba yi-luteinizing hormone-releasing hormone (LHRH) agonists, ethintela ukhuseleko kwencindi yedlala ebizwa ngokuba yihomoni yeluteinizing. Ii-agonists ze-LHRH, ngamanye amaxesha ezibizwa ngokuba zii-analogs ze-LHRH, ziiproteni zokwenziwa ezifanayo nolwakhiwo lwe-LHRH kwaye zibophelela kwi-LHRH receptor kwi-pituitary gland. (I-LHRH ikwabizwa ngokuba yi-gonadotropin-release hormone okanye i-GnRH, ke ii-agonists ze-LHRH zikwabizwa ngokuba yi-GnRH agonists.)
Ngokwesiqhelo, xa amanqanaba e-androgen emzimbeni esezantsi, i-LHRH ivuselela i-pituitary gland ukuba ivelise i-luteinizing hormone, ethi yona ivuselele amasende ukuba avelise i-androgens. I-LHRH agonists, njenge-LHRH yomzimba, ekuqaleni ivuselela imveliso yehomoni ye-luteinizing. Nangona kunjalo, ubukho obuqhubekayo bamanqanaba aphezulu e-agonists e-LHRH eneneni abangela ukuba incindi yebhinqa iyeke ukuvelisa i-hormone ye-luteinizing, kwaye ngenxa yoko amasende awakhuthazwanga ukuba avelise i-androgens.
Unyango nge-agonist ye-LHRH ibizwa ngokuba yi-castration yezonyango okanye i-chemical castration kuba isebenzisa iziyobisi ukufezekisa into efanayo ne-cast cast (orchiechtomy). Kodwa, ngokungafaniyo ne-orchiectomy, iziphumo zala machiza kwimveliso ye-androgen ziyagwetywa. Xa unyango luyekisiwe, imveliso ye-androgen ihlala iqala kwakhona.
I-LHRH agonists zinikwa ngenaliti okanye zifakwe phantsi kolusu. Ii-agonists ezine ze-LHRH zamkelwe ukunyanga umhlaza wedlala lobudoda e-United States: i-leuprolide, i-goserelin, i-triptorelin kunye ne-histrelin.
Xa abaguli befumana i-agonist ye-LHRH okokuqala, banokufumana into ebizwa ngokuba yi "testosterone flare." Olu konyuka okwethutyana kwinqanaba le testosterone kwenzeka ngenxa yokuba ii-agonists ze-LHRH ngokufutshane zibangela ukuba i-pituitary gland ikhuphe i-hormone eyongezelelweyo ngaphambi kokuthintela ukukhutshwa kwayo. Ukuqaqamba kungazenza mandundu iimpawu zeklinikhi (umzekelo, iintlungu zethambo, ureter okanye ukuphuma kwesinyi, kunye ne-spinal cord compression), enokuba yingxaki ethile kumadoda anomdlavuza we-Prostate. Ukonyuka kwe testosterone kuhlala kubalwa ngokunika olunye uhlobo lonyango lwehomoni olubizwa ngokuba yonyango lwe-antiandrogen kunye ne-LHRH agonist kwiiveki zokuqala zonyango.
- Iziyobisi ezibizwa ngokuba zi-LHRH antagonists, lolunye uhlobo lokuphoswa kwezonyango. Abachasi be-LHRH (ekwabizwa ngokuba ngabachasi be-GnRH) bathintela i-LHRH ekubambeni kwii-receptors zayo kwi-pituitary gland. Oku kuthintela ukugcinwa kwehomoni ye-luteinizing, emisa amasende ekuveliseni i-androgens. Ngokungafaniyo ne-LHRH agonists, abachasi be-LHRH ababangeli ukuba i-testosterone flare.
Umchasi omnye we-LHRH, u-degarelix, ngoku uvunyiwe ukuba anyange umhlaza weprostate e-United States. Inikwa ngenaliti.
- Estrogens (iihormoni ezikhuthaza iimpawu zesini sabasetyhini). Nangona ii-estrogens zikwanakho ukuthintela ukuveliswa kwe-androgen ngamasende, kunqabile ukuba zisetyenziswe namhlanje kunyango lomhlaza wedlala lobudoda ngenxa yeziphumo ebezingalindelekanga.
Unyango oluthintela isenzo se-androgens emzimbeni (ekwabizwa ngokuba lonyango lwe-antiandrogen) zihlala zisetyenziswa xa i-ADT iyeka ukusebenza. Olu hlobo lonyango lubandakanya:
- I-Androgen receptor blockers (ekwabizwa ngokuba yi-androgen receptor antagonists), ezingamayeza akhuphisana nee-androgens zokubopha kwi-androgen receptor. Ngokukhuphisana ngokubopha kwi-androgen receptor, olu nyango linciphisa amandla e-androgens ukukhuthaza ukukhula komhlaza wesifo seprotate.
Ngenxa yokuba i-androgen receptor blocker ayithinteli imveliso ye-androgen, kunqabile ukuba isetyenziselwe ukunyanga umhlaza wedlala lesinyi. Endaweni yoko, zisetyenziswa ngokudibeneyo ne-ADT (nokuba yi-orchiectomy okanye i-LHRH agonist). Ukusetyenziswa kwe-androgen receptor blocker ngokudibanisa ne-orchiectomy okanye i-agonist ye-LHRH ibizwa ngokuba yi-androgen blockade, i-androgen blockade epheleleyo, okanye i-androgen blockade iyonke.
I-Androgen receptor blockers ezivunyiweyo e-United States ukunyanga umhlaza wedlala lesinyi zibandakanya i-flutamide, i-enzalutamide, i-apalutamide, i-bicalutamide, kunye ne-nilutamide. Banikwa njengeepilisi ukuba ziginywe.
Unyango oluthintela ukuveliswa kwe-androgens emzimbeni wonke lubandakanya:
- I-Androgen synthesis inhibitors, ezingamachiza athintela ukuveliswa kwe-androgens ngamadlala eadrenal kunye neeseli zomhlaza wedlala ngokwazo, kunye nangamasende. Nokuba unyango okanye utyando alukhuselwa kuthintela amadlala eadrenal kunye neeseli zomhlaza wesibeleko ekuveliseni i-androgens. Nangona iimali ze-androgens ezi ziveliswa zincinci, zinokwanela ukuxhasa ukukhula kwezinye iicancer zomhlaza.
I-Androgen synthesis inhibitors ingathoba amanqanaba e testosterone emzimbeni womntu ukuya kwinqanaba elikhulu kunalo naluphi na unyango olwaziwayo. La machiza athintela ukuveliswa kwe testosterone ngokuthintela i-enzyme ebizwa ngokuba yi-CYP17. Le enzyme, efumaneka kumatyhalarha, kwiadrenal, nakwimithambo yamathumba, iyafuneka emzimbeni ukuze ivelise i testosterone kwi cholesterol.
Ii-androgen synthesis inhibitors ezintathu zamkelwe e-United States: i-acirateone acetate, ketoconazole, kunye ne-aminoglutethimide. Zonke zinikwa njengeepilisi ekufuneka ziginyiwe.
I-aciratone acetate yamkelwe ngokudibanisa ne-prednisone yokunyanga umhlaza weprostate onobungozi obunobungozi obukhulu kunye nomhlaza weprostate. Phambi kokuvunywa kwe-abiraterone kunye ne-enzalutamide, amachiza amabini avunyiweyo ngaphandle kwemhlaza yesinyi- ketoconazole kunye ne-aminoglutethimide-ngamanye amaxesha ayesetyenziselwa ngaphandle kwelebheli njengonyango lwesibini lomhlaza wesifo seprostate.
Unyango lwehomoni lusetyenziselwa njani ukunyanga umhlaza wedlala lobudoda?
Unyango lwehormone lunokusetyenziswa ngeendlela ezininzi ukunyanga umhlaza wedlala lobudoda, kubandakanya:
Umhlaza webala leprostate kwangoko kunye nomngcipheko ophakathi okanye omkhulu wokuphindaphinda. Amadoda anomhlaza webala le-Prostate kwinqanaba eliphakathi okanye elinomngcipheko ophakathi wokuphindaphindeka afumana unyango lwehomoni ngaphambi, ngexesha, kunye / okanye emva konyango lwe-radiation, okanye banokufumana unyango lwehomoni emva kweprotatectomy (utyando lokususa idlala lobudoda) (6) . Izinto ezisetyenziselwa ukumisela umngcipheko wokuphindaphinda komhlaza webala le-Prostate zibandakanya inqanaba lesisu (njengoko kulinganiswa ngamanqaku eGleason), ubungakanani apho ithumba lisasazeke nakwizicubu ezijikelezileyo, nokuba iiseli zesisu zifunyenwe kwii-lymph node ezikufutshane ngexesha lotyando.
Ubude bonyango kunyango lwehomoni kumanqanaba okuqala omhlaza wedlala lendlala luxhomekeke kumngcipheko wendoda wokuphindeka. Kumadoda anomhlaza ophakathi ongumngcipheko, unyango lwehomoni ngokubanzi lunikezelwa iinyanga ezi-6; kumadoda anezifo ezinobungozi obukhulu kunikwa ngokubanzi iinyanga ezili-18-24.
Amadoda afumana unyango lwehomoni emva kweprostatectomy aphila ixesha elide ngaphandle kokuphindaphinda kunamadoda ane-prostatectomy yedwa, kodwa awaphili ixesha elide (6). Amadoda afumana unyango lwehomoni emva konyango lwe-radiation engaphandle yomhlaza ophakathi okanye onomngcipheko omkhulu wesifo somhlaza wesibeleko uhlala ixesha elide, kokubini ngokubanzi nangaphandle kokuphindaphinda, kunamadoda anyangwa ngonyango lwemitha kuphela (6, 7). Amadoda afumana unyango lwehomoni ngokudibeneyo nonyango lwemitha aphile ixesha elide kunamadoda afumana unyango ngemitha kuphela (8). Nangona kunjalo, elona xesha lililo kunye nobude be-ADT, ngaphambi nasemva konyango lwe-radiation, alukasekwa (9, 10).
Ukusetyenziswa kwonyango lwehomoni (eyedwa okanye ngokudityaniswa nechemotherapy) ngaphambi kokuba iprostatectomy ingakhange iboniswe ukuba iyolula ixesha lokuphila kwaye ayisiyonyango oluqhelekileyo. Okubaluleke ngakumbi kwi-androgen blockade ngaphambi kwe-prostatectomy kufundwa kwizilingo zeklinikhi.
Umhlaza weprostate obuyileyo. Unyango lweHormone olusetyenziswe lodwa lunyango olusemgangathweni lwamadoda anomdlavuza we-Prostate ophindaphindiweyo njengoko kubhalwe yi-CT, i-MRI, okanye ukuskena kwethambo emva konyango kunyango lwe-radiation okanye i-prostatectomy. Unyango ngamanye amaxesha luyacetyiswa kumadoda ane "biochemical" ukuphindaphinda-ukunyuka kweprostate-specific antigen (PSA) kwinqanaba elilandela unyango lokuqala lwasekhaya ngoqhaqho okanye ngemitha-ngakumbi ukuba inqanaba le-PSA liphindwe kabini kwinyanga ezingaphantsi kwe-3 kwaye umhlaza awunawo usasazeko.
Uvavanyo lweklinikhi olungenamkhethe phakathi kwamadoda aphindaphindiweyo kwi-biochemical emva kwe-prostatectomy yafumanisa ukuba amadoda ayenonyango lwe-antiandrogen kunye nonyango lwemitha babengenakufane baphuhlise i-metastases okanye babulawe ngumhlaza wesibeletho okanye bebonke kunamadoda ane-placebo kunye ne-radiation (11). Nangona kunjalo, abaguli abanamaxabiso asezantsi e-PSA khange babonakale bexhamla kulongezo lonyango lwehomoni kwimitha. Olunye uvavanyo lwaklinikhi lwakutsha nje lubonise ukuba kumadoda anyuka amanqanaba e-PSA emva konyango lwasekhaya olwalusemngciphekweni omkhulu we-metastasis kodwa babengenabungqina besifo se-metastatic, ukongeza i-chemotherapy nge-docetaxel kwi-ADT kwakungekho ngaphezulu kwe-ADT ngokwamanqanaba aliqela okusinda ( 12).
Umhlaza ophambili okanye we-metastatic cancer. Unyango lweHormone olusetyenziswe lodwa lunyango oluqhelekileyo kumadoda afunyenwe enesifo se-metastatic (okt, isifo esisasazeke kwamanye amalungu omzimba) xa umhlaza wesibeletho ufunyaniswa okokuqala (13). Uvavanyo lweklinikhi lubonakalisile ukuba la madoda aphila ixesha elide xa anyangwa nge-ADT kunye ne-abiraterone / prednisone, enzalutamide, okanye i-apalutamide kunalapho anyangwa nge-ADT yodwa (14-17). Nangona kunjalo, ngenxa yokuba unyango lwehomoni lunokuba neziphumo ebezingalindelekanga, amanye amadoda akhetha ukungathathi unyango lwehomoni de iimpawu zikhule.
Iziphumo zokuqala zetyala elixhaswe yi-NCI elaliqhutywa ngamaqela amabini asebenzisana nomhlaza-i-Eastern Cooperative Oncology Group (i-ECOG) kunye ne-American College ye-Radiology Imaging Network (ACRIN) -acebisa ukuba amadoda anomhlaza wesifo seprostate womhlaza ofumana I-chemotherapy drug docetaxel ekuqaleni konyango olusemgangathweni lwehomoni iphila ixesha elide kunamadoda afumana unyango lwehormone kuphela. Amadoda anesifo se-metastatic esibonakalayo avele ukuba axhamle kakhulu kulongezo lwakwangoko lwe-docetaxel. Ezi ziphumo ziqinisekisiwe kutshanje kunye nokulandelwa kwexesha elide (18).
Ukuthanjiswa kweempawu. Unyango lweHormone ngamanye amaxesha lusetyenziselwa lodwa ukuphelisa okanye ukuthintela iimpawu zalapha kumadoda anomhlaza womhlaza wamatyhalarha anganyanzelekanga ukuba enze utyando okanye unyango ngemitha (19). Amadoda anjalo afaka abo banobomi obulinganiselweyo, abo banezicubu ezihamba phambili kwalapha ekhaya, kunye / okanye abo banezinye iimeko ezinzima zempilo.
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