Intergroup study EORTC-1532-gucg: A phase 2 randomized open-label study of oral darolutamide (ODM-201) vs. androgen deprivation therapy (ADT) with LHRH agonists or antagonist in men with hormone naive prostate cancer (PCa).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. TPS406-TPS406 ◽  
Author(s):  
Bertrand F. Tombal ◽  
Silke Gillessen ◽  
Yohann Loriot ◽  
Sandrine Marreaud ◽  
Laurence Collette ◽  
...  
Keyword(s):  
Side Effects ◽  
Androgen Deprivation Therapy ◽  
Competitive Inhibition ◽  
Single Agent ◽  
Objective Response ◽  
Androgen Deprivation ◽  
Total Testosterone ◽  
Disease Extent ◽  
Lhrh Analogues ◽  
Increased Risk

TPS406 Background: Androgen deprivation therapy (ADT) by LHRH analogues aims to lower serum testosterone. ADT is associated with several side effects that include hot flushes, depression, loss of libido, metabolic disturbances leading to an increase risk of cardiovascular disease, increased bone resorption leading to increased risk of osteoporosis and skeletal fracture. AR antagonists may circumvent these side effects by suppressing AR transcription by competitive inhibition of AR, without lowering systemic testosterone. In Europe, first generation AR antagonists bicalutamide 150 mg is registered for the treatment of non-metastatic hormone-naïve PCa. is a novel AR antagonist that is structurally distinct with higher AR-binding affinity compared to bicalutamide, enzalutamide, and apalutamide. The aim of this trial is to investigate the activity, safety and tolerability of darolutamide as single agent, as an alternative to LHRH analogues in men requiring ADT. Methods: EORTC-1532-GUCG (NCT02972060) will randomize 250 men with hormone-naïve PCa 1:1 to 600 mg (2× 300-mg tablets) bid of darolutamide1 or LHRH agonist or antagonist, stratified for type of ADT (agonist vs. antagonist), disease extent (measurable, non-measurable, vs. no metastasis) and age (≥70 vs < 70 years). Key inclusion criteria include histologically confirmed asymptomatic PCa (all stages) for whom continuous ADT is indicated for a minimum period of 24 weeks. Patients with up to 4 confirmed not visceral metastases, are allowed. Baseline total testosterone should be ≥ 8 nmol/L or 230 ng/dL. Primary endpoint is PSA response assessed at 24 weeks, defined as a ≥ 80% decline in PSA at week 24 in the darolutamide study arm. The ADT arm is used as an internal non comparative control. Key secondary endpoints include: Change in hormone-treatment related symptoms scale of the EORTC QLQ-PR25 at 24 weeks (comparison between arms); objective response rate at 24 weeks in patients with measurable disease at baseline, safety according to NCI-CTC version 4.0. Clinical trial information: NCT02972060.

scholarly journals Using Exercise and Nutrition to Alter Fat and Lean Mass in Men with Prostate Cancer Receiving Androgen Deprivation Therapy: A Narrative Review

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1664
Author(s):  
Rebekah L. Wilson ◽  
Dennis R. Taaffe ◽  
Robert U. Newton ◽  
Nicolas H. Hart ◽  
Philippa Lyons-Wall ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Side Effects ◽  
Physical Function ◽  
Androgen Deprivation Therapy ◽  
Cancer Progression ◽  
Lean Mass ◽  
Resting Metabolic Rate ◽  
Androgen Deprivation ◽  
Increased Risk ◽  
Patient Reported

Fat mass (FM) gain and lean mass (LM) loss are common side effects for patients with prostate cancer receiving androgen deprivation therapy (ADT). Excess FM has been associated with an increased risk of developing obesity-related comorbidities, exacerbating prostate cancer progression, and all-cause and cancer-specific mortality. LM is the predominant contributor to resting metabolic rate, with any loss impacting long-term weight management as well as physical function. Therefore, reducing FM and preserving LM may improve patient-reported outcomes, risk of disease progression, and ameliorate comorbidity development. In ADT-treated patients, exercise and nutrition programs can lead to improvements in quality of life and physical function; however, effects on body composition have been variable. The aim of this review was to provide a descriptive overview and critical appraisal of exercise and nutrition-based interventions in prostate cancer patients on ADT and their effect on FM and LM. Our findings are that FM gain and LM loss are side effects of ADT that could be reduced, prevented, or even reversed with the implementation of a combined exercise and nutrition program. However, the most effective combination of specific exercise and nutrition prescriptions are yet to be determined, and thus should be a focus for future studies.

598: Increased Risk of Newly Diagnosed Comorbidities in Prostate Cancer Patients Treated with Androgen Deprivation Therapy

2007 ◽  
Vol 177 (4S) ◽  
pp. 200-200 ◽  
Author(s):  
Andrea Gallina ◽  
Pierre I. Karakiewicz ◽  
Jochen Walz ◽  
Claudio Jeldres ◽  
Quoc-Dien Trinh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Androgen Deprivation Therapy ◽  
Androgen Deprivation ◽  
Newly Diagnosed ◽  
Increased Risk

scholarly journals Effect of androgen deprivation therapy on serum levels of sclerostin, Dickkopf-1, and osteoprotegerin: a cross-sectional and longitudinal analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alice Wang ◽  
Nishi Karunasinghe ◽  
Lindsay D. Plank ◽  
Shuotun Zhu ◽  
Sue Osborne ◽  
...  
Keyword(s):  
Androgen Deprivation Therapy ◽  
Longitudinal Analysis ◽  
Serum Levels ◽  
Androgen Deprivation ◽  
Mineral Density ◽  
Cross Sectional ◽  
Prognostic Features ◽  
Increased Risk ◽  
Positive Correlations ◽  
Dickkopf 1

AbstractAndrogen deprivation therapy (ADT) for men with prostate cancer (PCa) results in accelerated bone loss and increased risk of bone fracture. The aim of the present study was to evaluate serum bone markers—sclerostin, Dickkopf-1 (DKK-1) and osteoprotegerin (OPG), in a cohort of 88 PCa patients without known bone metastases, managed with and without ADT, and to analyse their relationship with bone mineral density (BMD) and sex steroids. The cross-sectional analysis between acute-, chronic- and former-ADT groups and PCa controls showed that sclerostin and OPG levels significantly differed between them (p = 0.029 and p = 0.032). Groups contributing to these significant changes were recorded. There were no significant differences in serum DKK-1 levels across the four groups (p = 0.683). In the longitudinal analysis, significant % decreases within groups were seen for DKK-1 [chronic-ADT (− 10.06%, p = 0.0057), former-ADT (− 12.77%, p = 0.0239), and in PCa controls group (− 16.73, p = 0.0022); and OPG levels in chronic ADT (− 8.28%, p = 0.003) and PCa controls group (− 12.82%, p = 0.017)]. However, % changes in sclerostin, DKK-1, and OPG did not differ significantly over 6-months across the evaluated groups. Sclerostin levels showed significant positive correlations with BMD at baseline in the ADT group, while in PCa controls this correlation existed at both baseline and 6-month time points. Sclerostin correlated negatively with testosterone in former ADT users and in PCa controls. Possible prognostic features denoted by parallel increases in sclerostin and BMD are discussed.

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.

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.

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