Selective estrogen receptor alpha agonist GTx-758 decreases testosterone with reduced side effects of androgen deprivation therapy in men with advanced prostate cancer.
Eur Urol
; 67(2): 334-41, 2015 Feb.
Article
em En
| MEDLINE
| ID: mdl-24968970
ABSTRACT
BACKGROUND:
A need remains for new therapeutic approaches for men with advanced prostate cancer, particularly earlier in the disease course.OBJECTIVE:
To assess the ability of an oral selective estrogen receptor α agonist (GTx-758) to lower testosterone concentrations compared with leuprolide while minimizing estrogen deficiency-related side effects of androgen-deprivation therapy. DESIGN, SETTING, ANDPARTICIPANTS:
Hormone-naive advanced prostate cancer patients were randomized to oral GTx-758 1000 mg/d, 2000 mg/d, or leuprolide depot. INTERVENTION GTx-758 and leuprolide. OUTCOME MEASUREMENTS AND STATISTICALANALYSIS:
The primary end point was the proportion of patients achieving total testosterone ≤ 50 ng/dl by day 60. Secondary end points included serum free testosterone, prostate-specific antigen (PSA), sex hormone-binding globulin, hot flashes, bone turnover markers, and insulin-like growth factor (IGF)-1 levels. RESULTS ANDLIMITATIONS:
Of 159 randomized patients, leuprolide reduced total testosterone to ≤ 50 ng/dl in a greater proportion of patients than GTx-758 by day 60 (43.4%, 63.6%, and 88.2% of subjects receiving GTx-758 1000 mg [p<0.001], GTx-758 2000 mg [p=0.004], and leuprolide, respectively). GTx-758 reduced free testosterone and PSA earlier and to a greater degree than leuprolide. GTx-758 led to fewer hot flashes, decreases in bone turnover markers, and alterations in IGF-1 compared with leuprolide. A higher incidence of venous thromboembolic events (VTEs) was seen with GTx-758 (4.1%) compared with leuprolide (0.0%).CONCLUSIONS:
Although leuprolide reduced total testosterone to ≤ 50 ng/dl in a greater proportion of patients compared with GTx-758, GTx-758 was superior in lowering free testosterone and PSA. GTx-758 reduced estrogen deficiency side effects of hot flashes, bone loss, and insulin resistance but with a higher incidence of VTEs. PATIENTSUMMARY:
This paper reports findings that leuprolide lowered total testosterone more than GTx-758 but that GTx-758 lowered free testosterone and prostate-specific antigen more than leuprolide. GTx-758 also reduced estrogen deficiency side effects, albeit at a higher rate of vascular events. TRIAL REGISTRATION Clinicaltrials.gov identifier NCT01615120.Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Testosterona
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Benzamidas
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Biomarcadores Tumorais
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Leuprolida
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Antineoplásicos Hormonais
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Moduladores Seletivos de Receptor Estrogênico
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Neoplasias Hormônio-Dependentes
Tipo de estudo:
Clinical_trials
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Aged80
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Humans
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Male
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Middle aged
País/Região como assunto:
America do norte
Idioma:
En
Revista:
Eur Urol
Ano de publicação:
2015
Tipo de documento:
Article