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.

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.

Survey of ADT-induced estrogen deficiency-related side effects in a contemporary cohort of men with advanced prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 235-235
Author(s):  
Robert H. Getzenberg ◽  
Mark C. Scholz ◽  
Alexandra Scholz ◽  
Mitchell S. Steiner
Keyword(s):  
Prostate Cancer ◽  
Side Effects ◽  
Hormonal Therapy ◽  
Advanced Prostate Cancer ◽  
Treatment Options ◽  
Hot Flashes ◽  
Estrogen Deficiency ◽  
Medical Need ◽  
Clinically Significant ◽  
The Impact

235 Background: Androgen Deprivation Therapy (ADT) is a mainstay in the treatment of advanced prostate cancer. ADT-induced estrogen deficiency related side effects may cause men to delay, pause, or discontinue ADT, increases morbidity and mortality, and can significantly impact quality of life. ADT-induced effects include hot flashes, bone loss and fractures, fatigue, decreased libido, and metabolic and lipid changes. Currently there are no FDA approved treatments for ADT-induced hot flashes in men with advanced prostate cancer. In this study, a survey was conducted on the impact of hot flashes, one of the hallmark ADT-induced estrogen deficiency effects, in a contemporary cohort. Methods: During the period of August/September 2019, 212 men with advanced prostate cancer on ADT participated in a digital survey conducted by the Prostate Cancer Research Institute (PCRI) focused on the frequency, severity and impact of their hot flashes. The men were at least 50 years of age with 61% being 70 or older. ADT types included LUPRONÒ(64%), ELIGARDÒ(12%), ZOLADEXÒ(7%) and other forms of hormonal therapy (17%). Results: Of the 212 men surveyed, 99% reported hot flashes with 80% indicating that they experience clinically significant, moderate to severe hot flashes. 77% of men reported that the number of hot flashes stayed the same or increased during their hormonal therapy. 37% of the men experienced more than 5 hot flashes per day and 23% indicated that they felt embarrassed about their hot flashes. Only 51% had either researched how to address their hot flashes or discussed them with their physician. Importantly, 16% considered halting ADT as a result of their hot flashes. Conclusions: This contemporary survey underscores the significant unmet medical need to treat moderate to severe hot flashes which occurred in 80% of the men studied. As about half of the men have not discussed their symptoms with a physician either because of embarrassment or lack of treatment options, the number of men with moderate to severe hot flashes appears to be greatly under-reported. As men on ADT are living longer with prostate cancer, finding an effective and safe treatment for debilitating hot flashes must be a priority.

scholarly journals Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer

2015 ◽  
Vol 33 (19) ◽  
pp. 2143-2150 ◽  
Author(s):  
Malcolm D. Mason ◽  
Wendy R. Parulekar ◽  
Matthew R. Sydes ◽  
Michael Brundage ◽  
Peter Kirkbride ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Androgen Deprivation Therapy ◽  
Advanced Prostate Cancer ◽  
Locally Advanced ◽  
Specific Antigen ◽  
Androgen Deprivation ◽  
Final Report ◽  
Locally Advanced Prostate Cancer

Purpose We have previously reported that radiotherapy (RT) added to androgen-deprivation therapy (ADT) improves survival in men with locally advanced prostate cancer. Here, we report the prespecified final analysis of this randomized trial. Patients and Methods NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110 was a randomized controlled trial of patients with locally advanced prostate cancer. Patients with T3-4, N0/Nx, M0 prostate cancer or T1-2 disease with either prostate-specific antigen (PSA) of more than 40 μg/L or PSA of 20 to 40 μg/L plus Gleason score of 8 to 10 were randomly assigned to lifelong ADT alone or to ADT+RT. The RT dose was 64 to 69 Gy in 35 to 39 fractions to the prostate and pelvis or prostate alone. Overall survival was compared using a log-rank test stratified for prespecified variables. Results One thousand two hundred five patients were randomly assigned between 1995 and 2005, 602 to ADT alone and 603 to ADT+RT. At a median follow-up time of 8 years, 465 patients had died, including 199 patients from prostate cancer. Overall survival was significantly improved in the patients allocated to ADT+RT (hazard ratio [HR], 0.70; 95% CI, 0.57 to 0.85; P < .001). Deaths from prostate cancer were significantly reduced by the addition of RT to ADT (HR, 0.46; 95% CI, 0.34 to 0.61; P < .001). Patients on ADT+RT reported a higher frequency of adverse events related to bowel toxicity, but only two of 589 patients had grade 3 or greater diarrhea at 24 months after RT. Conclusion This analysis demonstrates that the previously reported benefit in survival is maintained at a median follow-up of 8 years and firmly establishes the role of RT in the treatment of men with locally advanced prostate cancer.

The Role of Chromogranin A (CgA) in Monitoring Patients with Prostate Cancer Under Androgen Deprivation Therapy: Comparison with Prostatic Specific Antigen (PSA)

2008 ◽  
Vol 1 (2) ◽  
pp. 115-119
Author(s):  
Athanasios Bantis ◽  
Petros Sountoulides ◽  
Athanasios Zissimopoulos ◽  
Christos Kalaitzis ◽  
Stilianos Giannakopoulos ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Chromogranin A ◽  
Specific Antigen ◽  
Androgen Deprivation ◽  
Prostatic Specific Antigen
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