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 Prognostic role of docetaxel-induced suppression of free testosterone serum levels in metastatic prostate cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paula Kappler ◽  
Michael A. Morgan ◽  
Philipp Ivanyi ◽  
Stefan J. Brunotte ◽  
Arnold Ganser ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Cox Regression ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Serum Levels ◽  
Biologically Active ◽  
Free Form ◽  
Total Testosterone ◽  
The Impact

AbstractTo date, only few data concerning the biologically active, free form of testosterone (FT) are available in metastatic prostate cancer (mPC) and the impact of FT on disease, therapy and outcome is largely unknown. We retrospectively studied the effect of docetaxel on FT and total testosterone (TT) serum levels in 67 mPC patients monitored between April 2008 and November 2020. FT and TT levels were measured before and weekly during therapy. The primary endpoint was overall survival (OS). Secondary endpoints were prostate-specific antigen response and radiographic response (PSAR, RR), progression-free survival (PFS), FT/TT levels and safety. Median FT and TT serum levels were completely suppressed to below the detection limit during docetaxel treatment (FT: from 0.32 to < 0.18 pg/mL and TT: from 0.12 to < 0.05 ng/mL, respectively). Multivariate Cox regression analyses identified requirement of non-narcotics, PSAR, complete FT suppression and FT nadir values < 0.18 pg/mL as independent parameters for PFS. Prior androgen-receptor targeted therapy (ART), soft tissue metastasis and complete FT suppression were independent prognostic factors for OS. FT was not predictive for treatment outcome in mPC patients with a history of ART.

scholarly journals Comparison of serum testosterone levels in prostate cancer patients receiving LHRH agonist therapy with or without the removal of the prostate

2012 ◽  
Vol 6 (3) ◽  
pp. 183-186
Author(s):  
Seetha Venkateswaran ◽  
David Margel ◽  
Stanley Yap ◽  
Karen Hersey ◽  
Paul Yip ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Serum Testosterone ◽  
Lhrh Agonist ◽  
Agonist Therapy ◽  
Testosterone Levels

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.

Quality of life and LhRH agonist therapy among prostate cancer patients who experience PSA failure

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9093-9093
Author(s):  
K. F. Kline ◽  
O. Sartor ◽  
N. A. Dandade ◽  
N. J. Nonzee ◽  
B. D. Vicuna ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Cancer Patients ◽  
Lhrh Agonist ◽  
Agonist Therapy ◽  
Psa Failure ◽  
Health Related Qol ◽  
Health Related ◽  
Lhrh Therapy

9093 Background: Growing numbers of prostate cancer patients survive for extended periods of time after initial diagnosis and treatment. Many experience a biochemical relapse (“PSA failure”) some time after prostatectomy or pelvic radiation. LhRH agonist therapy can reduce PSA levels, but its impact on survival time and quality of life (QOL) is unclear. We evaluated these concerns among Veterans who experienced PSA Failure. Methods: Eligibility criteria included: receipt of primary therapy for prostate cancer followed by a PSA nadir and subsequent PSA rise to at least 0.2 ng/ml. Data sources include patients (interviewer administered survey instruments on health-related QOL at baseline, 3 and 12 months) and medical records (clinical and laboratory findings). Results: 69 patients from the Jesse Brown VA Medical Center in Chicago have enrolled in the study to date. At their baseline interviews, 30 patients (43.5%) were receiving LhRH agonists (46.1% of 39 African-American patients and 48.0% of 25 White patients). LhRH agonist patients reported worse health-related QOL in domains relevant to prostate cancer than watchful waiting (WW) patients ( Table ), including increased frequency of urination, difficulty controlling urination, greater erectile dysfunction, and more limits on sexual activity. LhRH agonist and WW patients reported similar levels of sexual satisfaction. Conclusion: Of the PSA failure patients studied in this sample, those receiving LhRH agonist therapy experience more problems with urinary and sexual function than those who opted for WW. Longitudinal study will provide information about whether the LhRH therapy causes these side effects, or whether symptomatic patients are more likely to choose LhRH therapy than those with few prostate cancer symptoms. [Table: see text] No significant financial relationships to disclose.

scholarly journals Surgical Castration in Hormone-Refractory Metastatic Prostate Cancer Patients Can Be an Alternative for Medical Castration

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Masayoshi Zaitsu ◽  
Mariko Yamanoi ◽  
Koji Mikami ◽  
Yuta Takeshima ◽  
Naohiko Okamoto ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Metastatic Prostate Cancer ◽  
Reduction Rate ◽  
Case Series ◽  
Total Testosterone ◽  
Lhrh Agonist ◽  
Hormone Refractory Prostate Cancer ◽  
Testosterone Levels ◽  
Hormone Refractory

Background. Most patients with metastatic prostate cancer are endocrinologically treated with LHRH agonist, but finally castration-refractory and hormone-refractory cancers occur. Serum testosterone levels get low to “the castration level” by LHRH agonists but may not get low enough against castration-refractory prostate cancer.Methods. As case series, twelve patients suffering from hormone-refractory prostate cancer continuously on LHRH agonist underwent surgical castration. Additionally, one hundred and thirty-nine prostate cancer patients on LHRH agonist or surgical castration were tested for serum total testosterone levels.Results. Surgical castration caused decrease in serum PSA in one out of 12 hormone-refractory prostate cancer patients with PSA reduction rate 74%. Serum total testosterone levels were below the sensitivity threshold (0.05 ng/mL) in 40 of 89 (44.9%) medically castrated patients and 33 of 50 (66.0%) surgically castrated patients (P=.20).Conclusion. Even hormone-refractory prostate cancer patients are candidates for surgical castration because of endocrinological, oncological, and economical reasons.

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.

Neoadjuvant hormone therapy for radical prostate radiotherapy: A case-matched study comparing bicalutamide to LHRH agonist therapy.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 88-88
Author(s):  
Jolyne O'Hare ◽  
Ursula McGivern ◽  
Cliona McDowell ◽  
Darren M. Mitchell ◽  
Gemma Corey ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Geometric Mean ◽  
Treated Group ◽  
Biochemical Failure ◽  
Lhrh Agonist ◽  
Radical Radiotherapy ◽  
Agonist Therapy ◽  
Psa Kinetics ◽  
Matched Study

88 Background: To assess and compare the biochemical failure free survival (BFFS), PSA kinetics and absolute PSA responses in men receiving radical radiotherapy for localized prostate cancer (RT) receiving either neoadjuvant bicalutamide or neoadjuvant LHRH agonist therapy. Methods: A retrospective review of consecutive cases with prostate cancer treated with BC monotherapy prior to radical radiotherapy was individually case matched to men treated with neoadjuvant LHRHa monotherapy from April 2004 to December 2008. PSA kinetics and absolute pre-RT, post neo-adjuvant hormone PSA (PRPH-PSA) level and subsequent BFFS were analyzed. Results: 65 men treated with BC monotherapy were individually matched with 65 men treated with LHRHa. The median follow-up was 44 months and 54 months respectively. There were no significant differences in pre-treatment patient or tumour characteristics. Statistically significant differences were noted between groups in the PRPH-PSA with a geometric mean of 2.0ng/ml (range 0.1 – 11.2ng/ml) for BC patients and 1.0ng/ml (range 0.1 – 11.1ng/ml) for LHRHa patients (p<0.001). The geometric mean PSA halving time during the neo-adjuvant period of 14.6weeks (range 2 – 160weeks) in the BC treated group was statistically significantly different when compared to the mean of 16.1 weeks (range 2.1-96.8 weeks) for LHRHa patients (p=0.056). There were however no differences in PSA velocity. A PRPH-PSA of <1.0ng/ml and <0.1ng/ml was seen in 16(24.6%) and 2 (3%) of the BC patients and 34(52.3%) and 3(4.6%) of LHRHa patients respectively. Phoenix biochemical failure was seen in 10(15.4%, 95%CI [8.6%, 26.1%]) and 8(12.3%, [6.4%, 22.5%) of BC and LHRHa patients respectively. Neither PRPH-PSA level nor PSA kinetics during the neo-adjuvant period predict for subsequent BFFS at this duration of follow-up. Conclusions: In this case-matched study, we found that although neo-adjuvant BC therapy did not result in equivalent PRPH-PSA suppression when compared to neo-adjuvant LHRHa alone, there was no difference in biochemical failure rates between the cohorts at an overall median follow-up of 44 months. Longer follow-up is required.

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