Selective Estrogen Receptor Alpha Agonist GTx-758 Decreases Testosterone with Reduced Side Effects of Androgen Deprivation Therapy in Men with Advanced Prostate Cancer

2015 ◽  
Vol 67 (2) ◽  
pp. 334-341 ◽  
Author(s):  
Evan Y. Yu ◽  
Robert H. Getzenberg ◽  
Christopher C. Coss ◽  
Marc M. Gittelman ◽  
Thomas Keane ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Estrogen Receptor ◽  
Side Effects ◽  
Androgen Deprivation Therapy ◽  
Advanced Prostate Cancer ◽  
Estrogen Receptor Alpha ◽  
Androgen Deprivation ◽  
Receptor Alpha ◽  
Alpha Agonist

scholarly journals Prevalence and predictors of cannabis use among men receiving androgen-deprivation therapy for advanced prostate cancer

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Ahmad Mousa ◽  
Michele Petrovic ◽  
Neil E. Fleshner
Keyword(s):  
Prostate Cancer ◽  
Side Effects ◽  
Androgen Deprivation Therapy ◽  
Advanced Prostate Cancer ◽  
Symptom Relief ◽  
Therapeutic Benefit ◽  
Androgen Deprivation ◽  
Cannabis Use ◽  
Testosterone Levels ◽  
Treatment Side Effects

Introduction: Prostate cancer patients receiving androgen-deprivation therapy (ADT) often experience a combination of disease symptoms and treatment side effects. The therapeutic use of cannabis to alleviate these side effects has not been studied, despite increasing patient interest. With the increasing availability of cannabis, it is important for clinicians to understand the prevalence, predictors, and perceived benefits of cannabis use among patients with prostate cancer. Methods: A total of 222 men undergoing ADT were assessed in this two-part study. In part one, the cannabis-use questionnaire was administered to 56 men, probing demographics, usage habits, perspectives, and degrees of symptom relief related to cannabis use. In part two, 191 cryopreserved urine samples were retrieved and analyzed for the presence of tetrahydrocannabidiol (THC) metabolite 11-nor-Δ9-THC-COOH. The respondents were then stratified into two groups, users vs. non-users, and statistical analyses were conducted. Results: Questionnaire data revealed that 23.2% of surveyed men had recently used cannabis. In contrast, 5.8% of men had detectable levels of THC metabolite in their urine. Combined questionnaire and urine data revealed that cannabis users were significantly younger (p=0.003) and had lower testosterone levels (p=0.003) than non-users. The majority of men experiencing common ADT side effects reported some degree of relief following cannabis use. Conclusions: Cannabis use among men with advanced prostate cancer receiving ADT is more prevalent than in the general population and the majority of other oncological cohorts. Lower testosterone levels and reported therapeutic benefit among cannabis users warrants confirmation in appropriate clinical trials.

scholarly journals Preclinical Characterization of a Novel Diphenyl Benzamide Selective ERα Agonist for Hormone Therapy in Prostate Cancer

Endocrinology ◽  
2012 ◽  
Vol 153 (3) ◽  
pp. 1070-1081 ◽  
Author(s):  
Christopher C. Coss ◽  
Amanda Jones ◽  
Deanna N. Parke ◽  
Ramesh Narayanan ◽  
Christina M. Barrett ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Side Effects ◽  
Androgen Deprivation Therapy ◽  
Advanced Prostate Cancer ◽  
Hot Flashes ◽  
Specific Antigen ◽  
Disease Free Survival ◽  
Estrogen Deficiency ◽  
Androgen Deprivation ◽  
Term Therapy

Androgen deprivation therapy (ADT) is the mainstay of treatment for advanced prostate cancer. ADT improves overall and disease-free survival rates, but long-term therapy is associated with severe side effects of androgen and estrogen depletion including hot flashes, weight gain, depression, and osteoporosis. Effective hormone reduction can be achieved without estrogen deficiency-related side effects by using therapy with estrogenic compounds. However, cardiovascular complications induced by estrogens coupled with the availability of LHRH agonists led to discontinuation of estrogen use for primary androgen deprivation therapy in the 1980s. New treatments for prostate cancer that improve patient outcomes without the serious estrogen deficiency-related toxicities associated with ADT using LHRH analogs are needed. Herein we describe a novel nonsteroidal selective estrogen receptor-α agonist designed for first-line therapy of advanced prostate cancer that in animal models induces medical castration and minimizes many of the estrogen deficiency-related side effects of ADT. The present studies show that orally administered GTx-758 reversibly suppressed testosterone to castrate levels and subsequently reduced prostate volume and circulating prostate-specific antigen in relevant preclinical models without inducing hot flashes, bone loss, thrombophilia, hypercoagulation, or increasing fat mass.

Phase 2 Trial of GTx-758, an Estrogen Receptor Alpha Agonist, in Men With Castration-Resistant Prostate Cancer

2020 ◽  
Vol 18 (6) ◽  
pp. 436-443 ◽  
Author(s):  
Evan Y. Yu ◽  
Michael L. Hancock ◽  
William Aronson ◽  
Thomas Flaig ◽  
Laurence Belkoff ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Phase 2 ◽  
Castration Resistant Prostate Cancer ◽  
Receptor Alpha ◽  
Phase 2 Trial ◽  
Castration Resistant ◽  
Alpha Agonist

scholarly journals Androgen deprivation therapy promotes an obesity-like microenvironment in periprostatic fat

2019 ◽  
Vol 8 (5) ◽  
pp. 547-558 ◽  
Author(s):  
Stefano Mangiola ◽  
Ryan Stuchbery ◽  
Patrick McCoy ◽  
Ken Chow ◽  
Natalie Kurganovs ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adipose Tissue ◽  
Side Effects ◽  
Androgen Deprivation Therapy ◽  
Cancer Progression ◽  
Tissue Level ◽  
Androgen Deprivation ◽  
Clinical Settings ◽  
Prostate Cancer Development ◽  
Transcriptional Changes

Prostate cancer is a leading cause of morbidity and cancer-related death worldwide. Androgen deprivation therapy (ADT) is the cornerstone of management for advanced disease. The use of these therapies is associated with multiple side effects, including metabolic syndrome and truncal obesity. At the same time, obesity has been associated with both prostate cancer development and disease progression, linked to its effects on chronic inflammation at a tissue level. The connection between ADT, obesity, inflammation and prostate cancer progression is well established in clinical settings; however, an understanding of the changes in adipose tissue at the molecular level induced by castration therapies is missing. Here, we investigated the transcriptional changes in periprostatic fat tissue induced by profound ADT in a group of patients with high-risk tumours compared to a matching untreated cohort. We find that the deprivation of androgen is associated with a pro-inflammatory and obesity-like adipose tissue microenvironment. This study suggests that the beneficial effect of therapies based on androgen deprivation may be partially counteracted by metabolic and inflammatory side effects in the adipose tissue surrounding the prostate.

scholarly journals The modern role of androgen deprivation therapy in the management of localised and locally advanced prostate cancer

2016 ◽  
Vol 9 (2_suppl) ◽  
pp. 24-29 ◽  
Author(s):  
Charlotte Gunner ◽  
Aziz Gulamhusein ◽  
Derek J Rosario
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Advanced Prostate Cancer ◽  
Locally Advanced ◽  
Androgen Deprivation ◽  
Locally Advanced Prostate Cancer ◽  
Curative Intent ◽  
Cardiovascular Morbidity And Mortality ◽  
Increased Risk

Introduction: Approximately 50% of men diagnosed with prostate cancer will be exposed to androgen deprivation therapy (ADT) at some stage. The role of ADT in the management of metastatic disease has long been recognised, and its place in the management of localised and locally advanced disease has become clearer in the past few years. Nevertheless, concerns remain that some men might not benefit from ADT in earlier-stage disease. The purpose of the current article is to provide a brief narrative review of the role of ADT as part of a strategy of treatment with curative intent, concentrating mainly on key recent developments in the area. Methods: Narrative literature review of key publications in the English language relating to ADT in the management of localised and locally advanced prostate cancer. Results: In locally advanced and high-risk localised prostate cancer, the use of ADT in combination with radiotherapy improves disease-specific and overall survival. There is no evidence to support the use of ADT in the treatment of low-risk localised prostate cancer. There appears to be an increased risk of cardiovascular morbidity and mortality associated with luteinizing hormone-releasing hormone agonists, particularly in men with pre-existing cardiovascular disease, but the relevance of this in the adjuvant/neoadjuvant setting is currently unclear. Conclusions: Future studies should focus on identification of men who are at risk from cardiovascular complications associated with ADT and on the comparison of radiotherapy with ADT versus surgery in the management of localised and locally advanced prostate cancer, particularly with regards to men with pre-existing comorbidities.

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