Gonadotropin-releasing hormone antagonist: A real advantage?

Kimura, Takahiro; Sasaki, Hiroshi; Akazawa, Kouhei; Egawa, Shin

doi:10.1016/j.urolonc.2015.04.013

Cited by 7 publications

(6 citation statements)

References 37 publications

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“…analyzed the six phase III prospective randomized trials and concluded that the risk of cardiac events within 1 year of initiating therapy was significantly lower for treatments with GnRH antagonists than for treatments with GnRH agonists in patients with pre‐existing CVD . However, the study was a post‐hoc analysis of the six phase III trials, and did not provide convincing evidence to show a clear superiority of GnRH antagonist, because the inclusion criteria and the intervention dosage was heterogenous, and the primary end‐point was not the incidence of CVD . A few basic studies showed possibilities of mechanisms of differences between GnRH agonists and antagonists; GnRH receptors that exist on T cells or in the urinary tract might play significant roles .…”

Section: Differences Between Gnrh Agonist and Antagonistmentioning

confidence: 99%

Metabolic changes in patients with prostate cancer during androgen deprivation therapy

Mitsuzuka

Arai

2017

Int J of Urology

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Androgen deprivation therapy continues to be widely used for the treatment of prostate cancer despite the appearance of new-generation androgen-receptor targeting drugs after 2000. Androgen deprivation therapy can alleviate symptoms in patients with metastatic prostate cancer and might have a survival benefit in some patients, but it causes undesirable changes in lipid, glucose, muscle or bone metabolism. These metabolic changes could lead to new onset or worsening of diseases, such as obesity, metabolic syndrome, diabetes mellitus, cardiovascular disease, sarcopenia or fracture. Several studies examining the influence of androgen deprivation therapy in Japanese patients with prostate cancer also showed that metabolic changes, such as weight gain, dyslipidemia or fat accumulation, can occur as in patients in Western countries. Efforts to decrease these unfavorable changes and events are important. First, overuse of androgen deprivation therapy for localized or elderly prostate cancer patients should be reconsidered. Second, intermittent androgen deprivation therapy might be beneficial for selected patients who suffer from impaired quality of life as a result of continuous androgen deprivation therapy. Third, education and instruction, such as diet or exercise, to decrease metabolic changes before initiating androgen deprivation therapy is important, because metabolic changes are likely to occur in the early androgen deprivation therapy period. Fourth, routine monitoring of weight, laboratory data or bone mineral density during androgen deprivation therapy are required to avoid unfavorable events.

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Section: Differences Between Gnrh Agonist and Antagonistmentioning

confidence: 99%

Metabolic changes in patients with prostate cancer during androgen deprivation therapy

Mitsuzuka

Arai

2017

Int J of Urology

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“…This method initially leads to a testosterone surge that can worsen the disease, but continuous administration of the agonist eventually downregulates the pituitary GnRH-R, regulating LH release and decreasing testosterone production [ 40 ]. On the other hand, GnRH antagonists act by directly binding to GnRH-R, thus avoiding the testosterone “flare” caused by GnRH agonists [ 41 , 42 ]. Even though it is clear that chronic stress leads to the suppression of GnRH, and GnRH constitutes a target for PC treatment, no study to date has directly examined the relationship between stress-induced modulation of the GnRH system and PC-related outcomes in a single in vivo model.…”

Section: Introductionmentioning

confidence: 99%

Stress alters the expression of cancer-related genes in the prostate

et al. 2017

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BackgroundProstate cancer is a major contributor to mortality worldwide, and significant efforts are being undertaken to decipher specific cellular and molecular pathways underlying the disease. Chronic stress is known to suppress reproductive function and promote tumor progression in several cancer models, but our understanding of the mechanisms through which stress contributes to cancer development and progression is incomplete. We therefore examined the relationship between stress, modulation of the gonadotropin-releasing hormone (GnRH) system, and changes in the expression of cancer-related genes in the rat prostate.MethodsAdult male rats were acutely or repeatedly exposed to restraint stress, and compared to unstressed controls and groups that were allowed 14 days of recovery from the stress. Prostate tissue was collected and frozen for gene expression analyses by PCR array before the rats were transcardially perfused; and brain tissues harvested and immunohistochemically stained for Fos to determine neuronal activation.ResultsAcute stress elevated Fos expression in the paraventricular nucleus of the hypothalamus (PVH), an effect that habituated with repeated stress exposure. Data from the PCR arrays showed that repeated stress significantly increases the transcript levels of several genes associated with cellular proliferation, including proto-oncogenes. Data from another array platform showed that both acute and repeated stress can induce significant changes in metastatic gene expression. The functional diversity of genes with altered expression, which includes transcription factors, growth factor receptors, apoptotic genes, and extracellular matrix components, suggests that stress is able to induce aberrant changes in pathways that are deregulated in prostate cancer.ConclusionsOur findings further support the notion that stress can affect cancer outcomes, perhaps by interfering with neuroendocrine mechanisms involved in the control of reproduction.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3635-4) contains supplementary material, which is available to authorized users.

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“…Regarding adverse events, the results from previous studies are controversial and confusing. Shore ND et al stated the potential advantages of GnRH antagonists in adverse events and oncological outcome [22], while Kimura T et al questioned the real advantage of that drug [23]. In this study, we hypothesized 3 months GnRH antagonist to be more advantageous than GnRH agonists owing to more rapid recovery of serum testosterone after discontinuation.…”

Section: Introductionmentioning

confidence: 85%

A comparative study on the efficacies of gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist in neoadjuvant androgen deprivation therapy combined with transperineal prostate brachytherapy for localized prostate cancer

et al. 2016

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BackgroundNeoadjuvant androgen deprivation therapy (ADT) has been suggested to confer several clinical benefits in patients with prostate cancer (PCa) undergoing transperineal prostate brachytherapy (TPPB). Unlike gonadotropin-releasing hormone (GnRH) receptor agonists, a GnRH antagonist such as degarelix can achieve castrate levels of testosterone without testosterone flare. However, normalization of serum testosterone levels following completion of neoadjuvant ADT in either form of treatment has never been compared in clinical trials.Methods/DesignThis is a single-center, open-label, randomized controlled study that will compare the efficacy and safety of degarelix with those of existing GnRH agonists combined with 125I-TPPB. A total of 56 patients with low/intermediate-risk clinically localized PCa will be enrolled and randomized to one of two treatment groups: the GnRH agonist group and the degarelix group. Patients in the GnRH agonist group will receive leuprorelin acetate or goserelin acetate, and those in the degarelix group will receive the initial dose of 240 mg as 2 subcutaneous injections of 120 mg each, and then 80 mg of maintenance doses every 4 weeks for 12 weeks. Those randomly assigned to the 12-week intervention period will subsequently undergo 48-weeks of follow-up after 125I-TPPB. The primary endpoint is defined as normalization of serum testosterone levels (>50 ng/dL) following completion of neoadjuvant ADT. All patients will be assessed every 4 weeks for the first 24 weeks, then every 12 weeks for the next 36 weeks after administrations of these drugs. Secondary endpoints are the proportion of normalized serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), the percent reduction in prostate specific antigen (PSA) compared with pretreatment levels, the percent reduction in total prostate volume (TPV) during neoadjuvant ADT, the percent increase in TPV after 125I-TPPB, the percent reduction in hemoglobin, serum alkaline phosphatase (ALP), changes in free testosterone and bone mineral content measurement, the proportion of patients who have serum testosterone levels over 50 ng/dL at 12 weeks following completion of neoadjuvant ADT, and the improvement of quality of life (QOL).DiscussionThe present study will provide additional insight regarding the benefit and potency of degarelix and will examine its potential as a new option for administration in neoadjuvant ADT.Trial registrationIdentification number: UMIN000015519.Registration date: October 24, 2014.

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Gonadotropin-releasing hormone antagonist: A real advantage?

Cited by 7 publications

References 37 publications

Metabolic changes in patients with prostate cancer during androgen deprivation therapy

Metabolic changes in patients with prostate cancer during androgen deprivation therapy

Stress alters the expression of cancer-related genes in the prostate

A comparative study on the efficacies of gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist in neoadjuvant androgen deprivation therapy combined with transperineal prostate brachytherapy for localized prostate cancer

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