Patient preference on once-daily oral versus injectable androgen deprivation therapy for Asian patients with advanced prostate cancer.

PURPOSE: The study aimed at investigating prostate cancer patients' choice of androgen deprivation treatment (ADT) and possible factors that would affect their preferences of ADT. METHODS: This was a single-centre cross-sectional study investigating the usage and preferences of ADT. Consecutives prostate cancer patients who were receiving injectable luteinizing hormone-releasing hormone (LHRH) agonist or antagonist were recruited from the prostate cancer clinic in a tertiary academic hospital. Patients who received bilateral orchidectomy or those who could not consent to the study were excluded. Disease characteristics, treatment information and patient background were documented. The survey collected information related to their change in ADT regimen, preferences on drug usage (routes and frequency of administration) and their reasons. A hypothetical set of three drug formularies was designed. Questions regarding patient preference and the contributing reasons raised in the format of questionnaire. RESULTS: 100 patients completed the survey. Most patients started with more frequent injections (3-monthly, 54%; 1-monthly, 38%) and switched to 6-monthly injections (89%) at the time of the survey. Primary reasons for the change were healthcare opinion (72%) and less frequent treatment (51%). Three options of ADT (oral daily, 1-monthly and 6-monthly injection) with the same efficacies and side effect profile were offered: 61% preferred 6-monthly injection, 1% preferred 1-monthly injection and 38% preferred oral regimen. When patients were informed of lower cardiovascular side effects in 1-monthly injection or daily oral drug, patients' preference was 56% (6-monthly), 6% (1-monthly), and 39% (oral). Patients with polypharmacy (more than 5 regular medications) were more inclined to choose injections (p = 0.025). Patient age, educational background, employment status, marriage status and disease status were not found to be statistically significant contributing factors to patient preference. CONCLUSION: 6-monthly ADT injection was the preferred ADT despite greater cardiovascular risks. Among 1-monthly or daily oral LHRH antagonist, more patients prefer oral option. Convenience factor was highly valued.

Treatment patterns and survival in metastatic castration-sensitive prostate cancer in the US Veterans Health Administration.

BACKGROUND: Limited real-world data exist on treatment patterns and outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC). METHODS: A retrospective cohort study was conducted, using the Veterans Health Administration claims database (April 2013-March 2018). Among 369,734 prostate cancer patients, we selected all men who developed metastases within 90 days before or after medical/surgical castration and who received androgen deprivation therapy (ADT). Patients were categorized into four cohorts: ADT-only (± <90-day nonsteroidal anti-androgen [NSAA] use), ADT + NSAA, ADT + docetaxel, and ADT + abiraterone. Main outcomes were treatment patterns, time-to-progression to metastatic castration-resistant disease, and overall survival. Multivariable analysis and sensitivity analysis were conducted. RESULTS: Of 1395 patients, 874 (63%) received ADT-only, 338 (24%) received ADT + NSAA, 108 (8%) received ADT + docetaxel, and 75 (5%) received ADT + abiraterone. Proportions on ADT-only and ADT + NSAA declined (from 66% to 60% and from 31% to 17%, respectively) over the study period, while proportions prescribed ADT + docetaxel or abiraterone increased from 3% to 9% and from 1% to 15%, respectively. Patients treated with ADT + NSAA had similar risks of castration-resistant disease (hazard ratio [HR] 1.05; 95% confidence interval [CI]: 0.87, 1.26) and overall mortality (HR 1.22; 95% CI: 0.97, 1.54) as ADT-only. CONCLUSIONS: Most patients with mCSPC initiating ADT received ADT-only or ADT + NSAA, despite the emergence of docetaxel and novel hormonal therapies. Even in the most recent period (2017 to early 2018), only 24% of men received intensified therapy with agents known to prolong survival versus ADT-only. These data in real-world clinical practice suggest substantial room for improved outcomes in patients with mCSPC.

Is there still a role for bilateral orchidectomy in androgen-deprivation therapy for metastatic prostate cancer?

Objective: To compare bilateral orchidectomy, as the classical 'gold standard' androgen-deprivation therapy (ADT), and ADT using a luteinising hormone-releasing hormone (LHRH) antagonist (degarelix) for the treatment of metastatic prostate cancer regarding their short-term biochemical efficacy, testosterone castrate level, tolerability, and effect on health-related quality of life (HRQoL). Patients and methods: A total of 60 patients with newly diagnosed metastatic prostate cancer were managed by either bilateral orchidectomy or degarelix injection as ADT. Both groups were compared according to their prostate-specific antigen (PSA) nadir and testosterone level at the 6-month follow-up. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) after 12 months. Results: Bilateral orchidectomy and degarelix showed comparable results for PSA reduction, but there was a statistically significantly lower castrate level of testosterone in the bilateral orchidectomy group. Using the EROTC QLQC-30, bilateral orchidectomy was associated with better HRQoL, better global health status, and better functional status. Conclusion: Bilateral orchidectomy resulted in lower castrate levels of testosterone, which may be associated with better disease control, together with better HRQoL and general health status compared to LHRH antagonist (degarelix). These results indicate that we should consider revisiting bilateral orchidectomy as a valuable and effective treatment option for ADT. Abbreviations: ADT: androgen-deprivation therapy; EORTC (QLQ-C30): European Organisation for Research and Treatment of Cancer (Quality of Life Questionnaire-Core 30); HRQoL: health-related quality of life.

More than reproduction: Central gonadotropin-releasing hormone antagonism decreases maternal aggression in lactating rats.

Gonadotropin-releasing hormone (GnRH) is a major regulator and activator of the hypothalamic-pituitary-gonadal axis. Many studies have demonstrated the importance of GnRH in reproduction and sexual behaviour. However, to date, only a single study shows an involvement of GnRH in maternal behaviour where a 30% reduction of GnRH neurones abolishes a mother's motivation to retrieve pups. On this basis, we aimed to investigate the effects of acute central GnRH receptor blockade in lactating rats on maternal care under non-stress and stress conditions, maternal motivation in the pup retrieval test, maternal anxiety on the elevated plus maze, and maternal aggression in the maternal defence test. We found that acute central infusion of a GnRH antagonist ([d-Phe2,6 ,Pro3 ]-luteinising hormone-releasing hormone; 0.5 ng 5 µL-1 ) impaired a mother's attack behaviour against a female intruder rat during the maternal defence test compared to vehicle controls. However, in contrast to the previous study on reduced GnRH neurones, acute central GnRH antagonism did not affect pup retrieval, nor any other parameter of maternal behaviour or maternal anxiety. Taken together, GnRH receptor activation is mandatory for protection of the offspring. These findings shed new light on GnRH as a neuropeptide acting not exclusively on the reproductive axis but, additionally, on maternal behaviour including pup retrieval and maternal aggression.

Recovery of Serum Testosterone Levels and Sexual Function in Patients Treated With Short-term Luteinizing Hormone-releasing Hormone Antagonist as a Neoadjuvant Therapy Before External Radiotherapy for Intermediate-risk Prostate Cancer: Preliminary Prospective Study.

INTRODUCTION: External beam radiation therapy (EBRT) with short-term androgen deprivation therapy is the standard of care for intermediate-risk prostate cancer patients. However, no study to date has evaluated the hormonal kinetics or sexual and hormonal function recovery after cessation of short-term luteinizing hormone (LH)-releasing hormone (LHRH) antagonist treatment. PATIENTS AND METHODS: Ten intermediate-risk prostate cancer patients (mean age, 69.9 years) were included. All patients received 4 months of LHRH antagonist (degarelix) treatment followed by EBRT. The testosterone, luteinizing hormone (LH), follicle-stimulating hormone, and prostate-specific antigen levels were measured and Expanded Prostate Cancer Index Composite questionnaires were completed before LHRH antagonist therapy at baseline; 1, 2, 3, and 4 months after the first injection of LHRH antagonist treatment; and every 2 months thereafter until 18 months. RESULTS: The testosterone levels were at the castration level at 1 month after the first LHRH antagonist injection. The median interval to recover a normal testosterone level (> 7.2 nmol/L) was 7 months after the last LHRH antagonist administration. The LH and follicle-stimulating hormone levels decreased but had increased more than twice above baseline at 15 months after the last LHRH antagonist injection. The sexual function and hormonal bother subdomain scores and sexual and hormonal domain scores decreased once after LHRH antagonist treatment but had significantly recovered thereafter (P < .05). CONCLUSION: In most patients, the testosterone level had normalized within 9 months after the last LHRH administration. Sexual and hormonal function recovered after short-term LHRH antagonist administration for neoadjuvant therapy before EBRT.

Therapeutic outcomes of the LHRH antagonists.

INTRODUCTION: Recently, LHRH antagonists have been established in the management of advanced prostate cancer, although the vast majority of Medical Oncologists and Urologists still prefer the LHRH agonists. Areas Covered: In this article we assess the therapeutic outcomes and the safety of the LHRH antagonists (mainly degarelix) compared to the LHRH agonists. Expert Commentary: Relevant studies demonstrated that LHRH antagonists are at least non-inferior to the LHRH agonists regarding therapeutic efficacy and safety, while there is potential benefit over the LHRH agonists in terms of cardiovascular morbidity and disease control. Disadvantages regarding formulation and frequency of administration are currently seem to be improving, as a 3-month depot of degarelix is evaluated and relugolix, an investigational orally administered is undergoing phase I studies, while the results of relative comparative studies are warranted.

Questionable oncologic benefits of degarelix.

INTRODUCTION: Luteinizing hormone releasing hormone (LhRh) antagonist degarelix has been approved by the Food and Drug Administration (FDA) for the treatment of advanced prostate cancer in 2008. However, the studies that followed such initial approval have several limitations. OBJECTIVE: To make a critical review of those publications. METHODS: Literature search on degarelix. RESULTS: The studies supporting the use of degarelix are criticized on the basis of selection bias in regards to the heterogeneous populations described, ad hoc analyses with low statistical merit, and the presentation of selected data that would appear to be favorable to the evaluated medication. In addition, those studies still have not shown that any of the data that they point out have any association with clinical benefit. CONCLUSION: The flawed methodology of these publications makes the evidence to support the use of degarelix rather weak.