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

Abstract

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.

Oral exposure of sulpiride promotes the proliferation of Brown‑Norway rat prostates

“…Additionally, Van Coppenolle et al (8) demonstrated that T levels are higher in controls compared with animals treated with sulpiride, which is not congruent with the aforementioned results. Previous studies have indicated that an increase in PRL inhibits gonadotrop-releasing hormone (GnRH) release from the hypothalamus and reduces LH release via a negative feedback regulatory mechanism (54,55). The structure and function of the prostate are influenced by the hypothalamus-pituitary-gonadal axis (56), while tissue growth and hormone secretion are primarily affected by T regulation (57).…”

Differences in sex hormone recovery profile after cessation of 12‐week gonadotropin‐releasing hormone antagonist versus agonist therapy

“…For all patients, TPPB was administered using an ultrasound-guided technique with either the Mick applicator or an intraoperatively built custom-linked seed technique. 11 The implant was planned to deliver a dose of at least 144 Gy to the clinical target volume, which included the prostatic gland and treatment margin. All participating patients completed TPPB.…”

Bone Tumors: Types and Treatments

“…This class of drug binds to the unique region in the N-terminal domain of both full-length and truncated constitutively active splice variant of AR [40]. c. ADT that effectively reduces the serum testosterone levels has been a core tool for treating metastatic and advanced prostate cancer [48]. However, neoadjuvant ADT has been suggested to have several advantages in prostate cancer patients undergoing transperineal prostate brachytherapy.…”

“…The agents that are mainly used as adjuvant ADT include estrogens, antiandrogen monotherapy, and combined androgen blockade (CAB) using antiandrogen plus a gonadotropin-releasing hormone receptor (GnRH) agonist. It has been reported that in comparison to GnRH agonist, degarelix, a GnRH receptor antagonist, is more efficient in achieving castration levels of testosterone and PSA, without risk of testosterone flare [48,49].…”