BPI19-009: Late Administration of Luteinizing Hormone-Releasing Hormone (LHRH) Agonists and Testosterone Levels >50NG/DL in Prostate Cancer

2019 ◽  
Vol 17 (3.5) ◽  
pp. BPI19-009
Author(s):  
Stuart Atkinson ◽  
Raoul S. Concepcion ◽  
John A. McLane ◽  
Deborah Boldt-Houle ◽  
Eleni Efstathiou
Keyword(s):  
Prostate Cancer ◽  
Standard Of Care ◽  
Lhrh Agonist ◽  
Contributing Factors ◽  
Luteinizing Hormone Releasing Hormone ◽  
Lhrh Agonists ◽  
Number Of Patients ◽  
Proven Efficacy ◽  
Clinical Benefits ◽  
T Values

Background: Achieving and maintaining effective testosterone (T) suppression is key to treatment of advanced prostate cancer (PCa), for which LHRH agonists are standard of care. Increasing evidence suggests maintaining very low T levels to <20 ng/dL with androgen deprivation therapy (ADT) is desirable and correlates with disease-specific survival in patients with advanced PCa. Consistent drug delivery is important in providing continuous T suppression throughout the course of treatment without T rising above castrate level (T breakthrough). However, T breakthrough may occur between administrations, especially if a subsequent dose is delayed. Contributing factors to late administrations may include scheduling challenges, shortage of available appointments, and increasing number of patients. While FDA approvals for ADT drugs are based on a 28-day month, insurers may mandate full calendar months between doses for reimbursement. This study explored timeliness of subsequent LHRH agonist administrations and its relationship with T breakthrough. Methods: A retrospective review of electronic medical records from January 1, 2007 and June 30, 2016 of 85,030 LHRH agonist administrations for PCa treatment was conducted to evaluate the percentage of late subsequent dosing and impact on frequencies of T breakthrough, defined as T>50 ng/dL. Late administrations were defined as those on or after day 33, 98, 129, and 195 for 1, 3, 4, and 6 month formulations, respectively. Results: 26.9% of all subsequent LHRH agonist administrations were late: 14.4% were ≤1 week late, 3.1% were between 1–2 weeks late, and 9.4% were >2 weeks late. While only 4% of T values exceeded 50 ng/dL when doses were administered early/on time, 21% of T values exceeded 50 ng/dL when administrations were late. Conclusions: Over a quarter of subsequent administrations were defined as late, leading to >20% incidence of T values exceeding 50 ng/dL. Considering the clinical benefits of maintaining effective T suppression throughout a course of ADT, clinicians should administer treatments within approved dosing instructions, routinely monitor T levels, and consider prescribing treatments with proven efficacy through the dosing interval to maintain T at castrate levels.

Late administration of luteinizing hormone-releasing hormone (LHRH) agonists and the impact on testosterone suppression in the real-world management of prostate cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 149-149
Author(s):  
Przemyslaw Twardowski ◽  
A. Oliver Sartor ◽  
John A. McLane ◽  
Debbie Boldt-Houle ◽  
Stuart Atkinson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lhrh Agonist ◽  
Duration Of Action ◽  
Luteinizing Hormone Releasing Hormone ◽  
Lhrh Agonists ◽  
Routine Monitoring ◽  
Prolonged Effect ◽  
Clinical Benefits ◽  
Low Testosterone ◽  
The Impact

149 Background: LHRH agonists are standard for androgen deprivation therapy (ADT) for advanced prostate cancer (PCa). Increasing evidence suggests maintaining very low testosterone (T) levels is desirable and correlate with disease-specific survival. However, T levels may rise above castrate level between administrations, especially if the next dose is delayed. A previous publication showed that subcutaneously-administered leuprolide acetate (LA) provided a longer duration of action than intramuscularly-administered LA past the dosing interval. This study evaluated the timeliness of LHRH agonist administrations and subsequent rate of T breakthroughs in PCa patients. Methods: A retrospective review of electronic medical records from 1/1/07-6/30/16 of 85,030 LHRH agonist administrations for PCa treatment was conducted to evaluate the percentage of late subsequent administrations and T tests with T > 50 ng/dL. A late administration was defined as occurring on or after day 33 (1 mo formulation), 98 (3 mo), 129 (4 mo), or 195 (6 mo). Descriptive statistics were used. Results: 26.9% of all subsequent LHRH agonist administrations were late: 14.4% were ≤ 1 week late, 3.1% were between 1 and 2 weeks late, and 9.4% were > 2 weeks late. 21% of T tests demonstrated T > 50 ng/dL when administrations were late, in contrast to only 4% of measured T levels exceeded 50 ng/dL when LHRH agonists were administered early or on time. Conclusions: Across LHRH agonists, greater than a quarter of subsequent administrations were defined as late. Among late administrations, about half were > 1 week late, and more than a third were > 2 weeks late. Late administrations were correlated with inadequate castration over 20% of the time. Considering the clinical benefits of maintaining effective T suppression during ADT, clinicians should administer treatments within approved dosing instructions, include routine monitoring of T levels, and consider prescribing treatments with proven prolonged effect through the dosing period to achieve T suppression to castrate levels.

Late dosing of luteinizing hormone-releasing hormone agonists (LHRH) and testosterone (T) levels >20 ng/dL in prostate cancer (PCa).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 31-31
Author(s):  
Przemyslaw Twardowski ◽  
Stuart Atkinson ◽  
Deborah Boldt-Houle ◽  
A. Oliver Sartor
Keyword(s):  
Electronic Medical Records ◽  
Medical Records ◽  
Specific Antigen ◽  
Lhrh Agonist ◽  
Luteinizing Hormone Releasing Hormone ◽  
Castration Resistant ◽  
Psa Testing ◽  
Proven Efficacy ◽  
Clinical Benefits ◽  
T Values

31 Background: LHRH agonists are the most frequently used drugs for the delivery of androgen deprivation therapy (ADT) for PCa. Evidence suggests achieving and sustaining T levels ≤20 ng/dL with ADT is desirable and correlates with improved disease-specific survival in advanced PCa patients. However, T levels may rise above castration level (50 ng/dL) between injections, especially if a subsequent dose is delayed. Increase in prostate-specific antigen (PSA) level on ADT may represent true disease progression to castration resistant PCa, or may be a result of late ADT dosing and inadequate T suppression. Current study evaluated timeliness of LHRH agonist dosing, subsequent rate of T breakthroughs and frequency of T/PSA testing prior to dosing in PCa patients. Methods: A retrospective review of electronic medical records and associated claims data (1/1/07-6/30/16) of LHRH agonist injections (n=85,030) evaluated the frequency of late dosing (defined as occurring after day 32, 97, 128, 194 for 1-, 3-, 4-, 6-month formulations, respectively), T tests >20 ng/dL and frequency of T/PSA tests prior to dosing. Results: 26.9% of injections were late: 14.4% were ≤1 week late, 3.1% were between 1-2 weeks late and 9.4% were >2 weeks late. 43% of T values exceeded 20 ng/dL for late injections; while only 21% exceeded this level for early/on-time injections. 83% of LHRH injections had a PSA value drawn prior to dosing; however, only 13% had a similarly timed T assessment. Conclusions: Overall, >25% of injections were late. For late injections, the proportion of T tests with T >20 ng/dL was higher compared to when the dosing was early/on-time. Late injections correlated with ineffective T suppression (>20 ng/dL) over 40% of the time. For all injections, T levels were not monitored as frequently as PSA levels. Considering the potential clinical benefits of maintaining effective T suppression throughout the course of ADT, clinicians should ensure treatments are delivered within approved dosing instructions, routinely monitor T levels and consider prescribing treatments with proven efficacy through the dosing interval to maintain T ≤20 ng/dL.

scholarly journals Luteinizing hormone-releasing hormone agonists for prostate cancer patients: routine clinical practice of Russian cancer urologists

2021 ◽  
Vol 17 (2) ◽  
pp. 83-92
Author(s):  
V. B. Matveev ◽  
B. Ya. Alekseev ◽  
B. Sh. Kamolov ◽  
A. S. Markova
Keyword(s):  
Prostate Cancer ◽  
Clinical Practice ◽  
Luteinizing Hormone ◽  
Testosterone Level ◽  
Routine Clinical Practice ◽  
Lhrh Agonist ◽  
Luteinizing Hormone Releasing Hormone ◽  
Lhrh Agonists ◽  
Hormone Sensitive ◽  
First Time

Background. Despite the recent amendments to the guidelines for the treatment of metastatic hormone-sensitive prostate cancer (PCa) implying standard use of luteinizing hormone-releasing hormone (LHRH) agonists in combination with chemotherapy or androgen inhibitors, androgen deprivation therapy (ADT) remains an essential component of treatment for advanced PCa. Testosterone target castration level of 20 ng/dL implies routine measurement of testosterone levels along with prostate-specific antigen (PSA) levels during ADT. It is particularly interesting to evaluate the frequency of achieving castration testosterone level in routine clinical practice. Objective: to assess the frequency of achieving castration testosterone level (20 ng/dL) and maintaining it after 6 months of therapy in patients with hormone-sensitive PCa receiving an LHRH agonist for the first time. Materials and methods. In 2019-2020, Russian Society of Cancer Urologists conducted a non-interventional prospective multicenter study (observational program) aimed to evaluate the efficacy of LHRH agonist (including buserelin, goserelin, leuprorelin or triptorelin) in routine clinical practice in Russia. This study involved 39 cancer urologists and 479 patients aged 18 years and older diagnosed with hormone-sensitive PCa, who started their ADT with LHRH agonists for the first time regardless of the disease stage and previous treatment. Patients received hormone therapy with an LHRH agonist for at least 6 months, visiting their doctor every 3 months (visit 1; visit 2: after 3 months; visit 3: after 6 months). Results. Patients received one of the following drugs: leuprorelin (3.75 mg; 7.5 mg; 22.5 mg; 45 mg; n = 225; 47,0 %), goserelin (3.6 mg; 10.8 mg; n = 132; 27.5 %), buserelin (3.75 mg; n = 67; 14.0 %), and triptorelin (3.75 mg; 11.25 mg; n = 55; 11.5 %). Of 479 patients, 186 (38.8 %) received combination treatment with bicalutamide, 12 (2.5 %) with fluta-mide, 54 (11.3 %) with zoledronic acid, and 11 (2.3 %) with denosumab. Among 146 patients with metastatic PCa, a combination of ADT plus docetaxel was administered to 30 participants (20.6 %), ADT plus abiraterone to 8 participants (5.5 %), and ADT plus enzalutamide to 2 participants (1.4 %). After 6 months of therapy, mean PSA level decreased by 94.2 % (from baseline 118.12 ng/mL to 6.87 ng/mL). Mean testosterone level was 19.0 ng/dL (range: 0.029-100 ng/dL). Among 430 patients, the targeted testosterone level <20 ng/dL was achieved in 257 individuals (59.8 %); the level of 20-50 ng/dL was achieved in 158 individuals (36.7 %); and fifteen patients (3.5 %) had their testosterone level >50 ng/dL. The incidence of adverse events was low; most of them were mild. Conclusion. Our findings suggest that not all patients achieve targeted testosterone level of <20 ng/dL, which corroborates the need for routine monitoring of testosterone levels during therapy to ensure its timely correction. We observed frequent administration of ADT with maximum androgen blockade. In patients with metastatic PCa, the use of standards for combination treatment with docetaxel and androgen inhibitors is limited.

scholarly journals Practical differences between luteinizing hormone-releasing hormone agonists in prostate cancer: perspectives across the spectrum of care

2017 ◽  
Vol 10 (2) ◽  
pp. 51-63 ◽  
Author(s):  
Davide Meani ◽  
Mladen Solarić ◽  
Harri Visapää ◽  
Rose-Marie Rosén ◽  
Robert Janknegt ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Luteinizing Hormone ◽  
Cancer Patients ◽  
Healthcare Management ◽  
Lhrh Agonist ◽  
Specific Storage ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Lhrh Agonists ◽  
Solid Implants

Background: Androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) agonists is well established for the treatment of men with metastatic prostate cancer. As clear differences in efficacy, safety, or tolerability between the available LHRH agonists are lacking, the healthcare management team needs to look to practical differences between the formulations when selecting therapy for their patients. Moreover, as the economic burden of prostate cancer rises alongside earlier diagnosis and improved survival, the possibility for cost savings by using products with specific features is growing in importance. Methods: A review was conducted to summarize the information on the different LHRH agonist formulations currently available and offer insight into their relative benefits and disadvantages from the perspectives of physicians, a pharmacist, and a nurse. Results: The leuprorelin acetate and goserelin acetate solid implants have the advantage of being ready to use with no requirement for refrigeration, whereas powder and microsphere formulations have to be reconstituted and have specific storage or handling constraints. The single-step administration of solid implants, therefore, has potential to reduce labor time and associated costs. Dosing frequency is another key consideration, as administering the injection provides an opportunity for face-to-face interaction between the patient and healthcare professionals to ensure therapy is optimized and give reassurance to patients. Prostate cancer patients are reported to prefer 3- or 6-monthly dosing, which aligns with the monitoring frequency recommended in European Association of Urology guidelines and has been shown to result in reduced annual costs compared with 1-month formulations. Conclusions: A number of practical differences exist between the different LHRH agonist preparations available, which may impact on clinical practice. It is important for healthcare providers to be aware and carefully consider these differences when selecting treatments for their prostate cancer patients.

scholarly journals Treatment Landscape of Nonmetastatic Castration-Resistant Prostate Cancer: A Window of Opportunity

2021 ◽  
Vol 11 (11) ◽  
pp. 1190
Author(s):  
Fernando López-Campos ◽  
Antonio Conde-Moreno ◽  
Marta Barrado Los Arcos ◽  
Antonio Gómez-Caamaño ◽  
Raquel García-Gómez ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Guidelines ◽  
Standard Of Care ◽  
Phase Iii ◽  
Metastatic Progression ◽  
Castration Resistant Prostate Cancer ◽  
Phase Iii Clinical Trials ◽  
Castration Resistant ◽  
Medical Need ◽  
Clinical Benefits

The treatment for nonmetastatic castration-resistant prostate cancer (nmCRPC) is a highly unmet medical need. The classic treatment approach for these patients—androgen deprivation therapy (ADT) alone—until metastatic progression is now considered suboptimal. Several randomized phase III clinical trials have demonstrated significant clinical benefits—including significantly better overall survival (OS)—for treatments that combine ADT with apalutamide, enzalutamide, and darolutamide. As a result, these approaches are now included in treatment guidelines and are considered a standard of care. In the present article, we discuss the changing landscape of the management of patients with nmCRPC.

scholarly journals Clinical significance of suboptimal hormonal levels in men with prostate cancer treated with LHRH agonists

2013 ◽  
Vol 7 (3-4) ◽  
pp. e226-30 ◽  
Author(s):  
Jun Kawakami ◽  
Alvaro Morales
Keyword(s):  
Prostate Cancer ◽  
Blood Sample ◽  
Serum Levels ◽  
Total Testosterone ◽  
Lhrh Agonist ◽  
Agonist Therapy ◽  
Hormone Levels ◽  
Lhrh Agonists ◽  
Significant Difference ◽  
Hormonal Levels

Purpose:  We examined the serum levels of testosterone (T) (total and bioavailable) dehydroepiandrosterone (DHEA), follicle stimulating (FSH), luteinizing (LH), and prostate specific antigen (PSA) in men receiving treatment with  luteinizing hormone releasing-hormone (LHRH) agonists for metastatic prostate cancer, to determine the efficacy of these agents in lowering T levels and whether a possible  relationship exists between PSA values, as a surrogate measure of tumor activity, and hormone levels.   Materials and Methods:  This was a single center prospective study of patients on LHRH agonists.  Of all 100 eligible patients, 31 did not qualify: 10 were receiving their first injection, 13 were on intermittent hormonal therapy, 7 refused to enter the trial, and 1 patient’s blood sample was lost.  Therefore, 69 patients were included in the final analysis.  Each patient had their blood sample drawn immediately before the administration of a LHRH agonist. The new proposed criteria of <20ng/dL (0.69 nmol/L) of total testosterone was used to define optimal levels of the hormone in this population.   Results: Of the 69 patients, 41 were on goserelin injections, 21 on leuprolide, and 7 on buserelin.  There was no statistical difference in hormone levels between any of the medications.  Overall, 21% of patients failed to reach optimal levels of total testosterone. PSA levels were higher in this group.  There was a statistically significant correlation between PSA and testosterone levels as well as between PSA and  FSH.  Serum levels of PSA however, did not correlate with those of bio-available testosterone.   Conclusions: Failure to reach optimal levels of testosterone occurs in patients on LHRH agonist therapy.  Higher PSA values are more commonly found in patients with sub-optimal levels of testosterone receiving LHRH analogs but the clinical importance of this finding has not been established.  There is no significant difference with respect to hormonal levels reached among patients on a variety of LHRH agonists.  Total testosterone determinations should be considered in patients on LHRH agonist therapy, particularly when the PSA values begin to rise since it may lead to further beneficial hormonal manipulation.

Expression of LHRH receptors in prostate cancer cells prior to therapy, following castration, or following treatment with LHRH agonists

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5163-5163
Author(s):  
S. Liu ◽  
A. V. Schally ◽  
S. Xiong ◽  
R. Cote ◽  
D. Hawes ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Receptor Expression ◽  
Localized Prostate Cancer ◽  
Prolonged Treatment ◽  
Lhrh Agonist ◽  
Prostate Cancer Cells ◽  
Agonist Therapy ◽  
Lhrh Agonists ◽  
Lhrh Receptor

5163 Background: In the treatment of advanced prostate cancer, the effects of luteinizing hormone releasing hormone (LHRH) agonists are mediated through the down-regulation of pituitary LHRH receptors, inhibiting the pituitary-gonadal axis. Several groups have demonstrated LHRH receptor expression on prostate cancer cells. These tumoral receptors have been shown to mediate direct inhibitory effects in vitro. That expression of LHRH receptors persists in the castrate resistant state. To date, there is no information on LHRH receptor expression on the prostate after LHRH agonist therapy. This study investigates the expression of LHRH receptors following prolonged exposure to LHRH agonists. Methods: Expression of LHRH receptors was determined using immunohistochemistry and the intensity was graded on a scale from zero to 3. The expression was analyzed in three cohorts of patients: (1) 47 men with localized prostate cancer treated with radical prostatectomy with no hormone therapy, (2) 61 men with localized prostate cancer treated with neoadjuvant LHRH agonists for varying duration prior to prostatectomy, and (3) 22 men with metastatic prostate cancer who received a palliative transurethral resection of the prostate after clinical progression. In the final cohort, 15 men were treated with castration and 7 were treated with LHRH agonists. Results: 45 of 47 hormone naïve samples (95.7%) demonstrated LHRH receptor expression. Statistical analysis revealed a correlation between strong receptor expression and higher pathologic tumor stage as well as shorter overall survival. 60 of 61 samples treated with neoadjuvant LHRH agonist therapy (98.4%) demonstrated LHRH receptor expression. All 22 samples from patients with metastatic disease demonstrated LHRH receptor expression. The majority of these samples demonstrated moderate to strong intensity. Conclusions: LHRH receptors are expressed on prostate cancers cells of hormone naïve and castrated patients. The expression of these receptors appears to persist despite prolonged treatment with LHRH agonists. The continued expression of these receptors supports the concept of targeting prostatic LHRH receptors to deliver cytotoxic therapy based on LHRH analogs, such as AN-152. [Table: see text]

scholarly journals Luteinizing hormone-releasing hormone antagonists for urinary obstruction in prostate cancer

2013 ◽  
Vol 7 (9-10) ◽  
pp. 648 ◽  
Author(s):  
Patricia Tai ◽  
Asim Amjad ◽  
Rashmi Koul ◽  
Evgeny Sadikov ◽  
Arbind Dubey
Keyword(s):  
Prostate Cancer ◽  
Luteinizing Hormone ◽  
Serum Creatinine ◽  
Urinary Tract Obstruction ◽  
Specific Antigen ◽  
Pelvic Mass ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Lhrh Agonists ◽  
Lhrh Antagonists

Luteinizing hormone-releasing hormone (LHRH) antagonists rapidly reduce testosterone and are preferred to LHRH agonists in situations when early response is important. The lack of flare reaction, as compared to LHRH agonists, is particularly desirable as it would not aggravate the problem. A 78-year-old man presented with symptoms of urinary tract obstruction. He had a prostate-specific antigen (PSA) of 91.3 ug/L and serum creatinine 146 umol/L. He had a large pelvic mass due to histologically confirmed prostate cancer, resulting in moderate left hydronephrosis and deteriorating renal function (serum creatinine of 163 umol/L). He was started on combined degarelix and bicalutamide on the day of consultation (day 0). The hydronephrosis resolved on the repeat computerized tomography scan performed on day 10. Serum creatinine normalized to under 130 umol/L on day 18. The PSA fell to 11 ug/L on day 18, 2.8 ug/L on day 28, and 0.5 ug/L on day 53. Therefore, LHRH antagonists are particularly useful in urgent situations. It is the preferred choice in these circumstances.

Sign in / Sign up

Export Citation Format

Share Document