Advanced Hormone-sensitive Prostate Cancer Research Articles

Re: Is There a Benefit of Additional Docetaxel, Abiraterone, Celecoxib, or Zoledronic Acid in Initial Treatments for Patients Older Than 70 Years with Hormone-Sensitive Advanced Prostate Cancer? A Meta-Analysis.

No AccessJournal of UrologyUrological Survey1 Nov 2020Re: Is There a Benefit of Additional Docetaxel, Abiraterone, Celecoxib, or Zoledronic Acid in Initial Treatments for Patients Older Than 70 Years with Hormone-Sensitive Advanced Prostate Cancer? A Meta-Analysis Tomas L. GrieblingMD, MPH Tomas L. GrieblingTomas L. Griebling More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001248AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Re: Is There a Benefit of Additional Docetaxel, Abiraterone, Celecoxib, or Zoledronic Acid in Initial Treatments for Patients Older Than 70 Years with Hormone-Sensitive Advanced Prostate Cancer? A Meta-Analysis." The Journal of Urology, 204(5), p. 1073 © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 204Issue 5November 2020Page: 1073-1073 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tomas L. Griebling More articles by this author Expand All Advertisement PDF DownloadLoading ...

How does early compare with deferred standard androgen suppression therapy (AST) for men with advanced hormone-sensitive prostate cancer?

How does early compare with deferred standard androgen suppression therapy (AST) for men with advanced hormone-sensitive prostate cancer?

Gleason score and docetaxel response in advanced hormone-sensitive prostate cancer: The lower the better

Recently, three randomized controlled trials evaluated the addition of docetaxel to ADT in advanced hormone-sensitive prostate cancer (aHSPC). Interestingly, all trials showed a trend towards improved OS in the subgroup of patients with Gleason <8 tumors. We herein performed a meta-analysis of these trials to assess the OS benefit of docetaxel in different Gleason score groups (<8 vs ≥8). We searched the Pubmed and Medline databases and ASCO conference proceedings (through February 1st 2018) for relevant trials. For each study, median OS values and hazard ratios (HR) with 95% confidence intervals (CI) collected across different Gleason score groups. We combined the HRs from each of the three eligible trials in the meta-analysis using the random-effect model. Three eligible studies were included in the analyses (CHAARTED, GETUG-AFU-15, and STAMPEDE). In the meta-analysis of three studies, docetaxel-based chemotherapy plus ADT was associated with improved OS [HR: 0.74; 95% CI: 0.62-0.87; p<0.001]. Among patients with tumor Gleason score <8, addition of docetaxel to ADT significantly improved overall survival [HR: 0.66, 95% CI: 0.52–0.85, p=0.001]. Although there was a trend towards improved OS with docetaxel in patients with Gleason score of ≥8, the magnitude of risk reduction was lower and did not achieve statistical significance [HR: 0.81, 95% CI: 0.64–1.02, p=0.066]. In this meta-analysis, OS benefit with the addition of docetaxel to ADT was more prominent in Gleason score <8 tumors. We propose that Gleason score can be a useful criteria for treatment selection in patients with aHSPC.

Early versus deferred standard androgen suppression therapy for advanced hormone-sensitive prostate cancer.

Standard androgen suppression therapy (AST) using surgical or medical castration is considered a mainstay of advanced hormone-sensitive prostate cancer treatment. AST can be initiated early when disease is asymptomatic or deferred when patients suffer symptoms of disseminated prostate cancer. To assess the effects of early versus deferred standard AST for advanced hormone-sensitive prostate cancer. For this Cochrane Review update, we performed a comprehensive search of multiple databases (CENTRAL, MEDLINE, Embase, Web of Science; last searched November 2018) and two clinical trial registers, with no restrictions on the language of publication or publication status. We also searched bibliographies of included studies and conference proceedings (last searched January 2019). We included all randomised controlled trials (RCTs) with a direct comparison of early versus deferred standard AST. We excluded all other study designs. Participants included had advanced hormone-sensitive prostate cancer receiving surgical or medical castration. Two review authors independently classified studies and abstracted data. The primary outcomes were time to death of any cause and serious adverse events. Secondary outcomes were time to disease progression, time to death from prostate cancer, adverse events and quality of life. We performed statistical analyses using a random-effects model and assessed the certainty of evidence according to GRADE. We performed subgroup analyses for advanced but non-metastatic disease (T2-4/N+ M0), metastatic disease (M1), and prostate-specific antigen (PSA) relapse. We identified seven new RCTs since publication of the original review in 2002. In total, we included 10 RCTs.Primary outcomesEarly AST probably reduces the risk of death from any cause over time (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.75 to 0.90; moderate-certainty evidence; 4767 participants). This corresponds to 57 fewer deaths (95% CI 80 fewer to 31 fewer) per 1000 participants at 5 years for the moderate risk group and 23 fewer deaths (95% CI 32 fewer to 13 fewer) per 1000 participants at 5 years in the low risk group. We downgraded for study limitations. Early versus deferred AST may have little or no effect on serious adverse events (risk ratio (RR) 1.05, 95% CI 0.95 to 1.16; low-certainty evidence; 10,575 participants) which corresponds to 6 more serious adverse events (6 fewer to 18 more) per 1000 participants. We downgraded the certainty of evidence for study limitations and selective reporting.Secondary outcomesEarly AST probably reduces the risk of death from prostate cancer over time (HR 0.69, 95% CI 0.57 to 0.84; moderate-certainty evidence). This corresponds to 62 fewer prostate cancer deaths per 1000 (95% CI 87 fewer to 31 fewer) at 5 years for the moderate risk group and 24 fewer death from prostate cancer (95% CI 34 fewer to 12 fewer) per 1000 men at 5 years in the low risk group. We downgraded the certainty of evidence for study limitations.Early AST may decrease the rate of skeletal events (RR 0.37, 95% CI 0.17 to 0.80; low-certainty evidence) corresponding to 23 fewer skeletal events per 1000 (95% CI 31 fewer to 7 fewer). We downgraded for study limitations and imprecision. It may also increase fatigue (RR 1.41, 95% CI 1.23 to 1.62; low-certainty evidence), corresponding to 31 more men with this complaint per 1000 (95% CI 18 more to 48 more). We downgraded for study limitations and imprecision. It may increase the risk of heart failure (RR 1.90, 95% CI 1.09 to 3.33; low-certainty evidence) corresponding to 27 more events per 1000 (95% CI 3 more to 69 more). We downgraded the certainty of evidence for study limitations and imprecision.Global quality of life is probably similar after two years as assessed with the EORTC QLQ-C30 (version 3.0) questionnaire (mean difference -1.56, 95% CI -4.50 to 1.38; moderate-certainty evidence) with higher scores reflecting better quality of life. We downgraded the certainty of evidence for study limitations. Early AST probably extends time to death of any cause and time to death from prostate cancer. It may slightly decrease the rate of skeletal events. Rates of serious adverse events and quality of life may be similar. It may increase fatigue and may increase the risk of heart failure. Better quality trials would be particularly important to better understand the outcomes related to possible treatment-related harm, for which we only found low-certainty evidence.

Is There a Benefit of Addition Docetaxel, Abiraterone, Celecoxib, or Zoledronic Acid in Initial Treatments for Patients Older Than 70 Years With Hormone-sensitive Advanced Prostate Cancer? A Meta-analysis.

Results from large randomized controlled trials combining docetaxel, abiraterone, celecoxib, or bisphosphonates with androgen deprivation therapy (ADT) in hormone-sensitive prostate cancer have emerged. However, in our knowledge, few data are available in patients older than 70 years. Therefore, we undertook a meta-analysis of all published phase III studies. We performed a PubMed search using the keywords: "hormone sensitive prostate cancer," "phase III studies," "docetaxel," "abiraterone," "celecoxib," and "bisphosphonates." We also screened American Society of Clinical Oncology and European Society for Medical Oncology proceedings. Combination therapies were compared with ADT alone. The efficacy outcomes were overall survival (OS) and progression-free survival (PFS). Hazard ratios (HRs) with their 95% confidence intervals (CIs) were collected from the studies and pooled. A hazard ratio of less than 1.00 favored the combination group. This meta-analysis included 8 studies: 3 assessed docetaxel (CHAARTED, STAMPEDE arm E and C), 2 others assessed abiraterone (LATITUDE and STAMPEDE arm G); 2 others assessed celecoxib (STAMPEDE arm D and F), and the last one assessed zoledronic acid alone (STAMPEDE arm B). Our meta-analysis included 2264 patients (86% with metastases). Concerning age, we chose a cutoff of 70 years, corresponding to the available data for each study. The performance index was 0 to 1 for about 90% of patients. Overall, in patients > 70 years old, the addition of docetaxel statistically improved PFS (HR, 0.51; 95% CI, 0.42-0.61) but not OS (HR, 0.86; 95% CI, 0.69-1.07). The addition of abiraterone to ADT also statistically improved PFS (HR, 0.49; 95% CI, 0.37-0.64) but not OS (HR, 0.85; 95% CI, 0.67-1.08), as well as the addition of celecoxib (HR, 0.67; 95% CI, 0.53-0.85 and HR, 0.95; 95% CI, 0.73-1.25, respectively). The addition of zoledronic acid did not improve PFS or OS (HR, 0.78; 95% CI, 0.61-1.00 and HR, 0.99; 95% CI, 0.71-1.38, respectively). The addition of docetaxel, abiraterone, or celecoxib to ADT significantly increased PFS in older men with hormone-sensitive advanced prostate cancer. However, the benefit in OS is not statistically significant. Further studies are needed to define the best first-line strategy in this subgroup.

Serum Proteomics on the Basis of Discovery of Predictive Biomarkers of Response to Androgen Deprivation Therapy in Advanced Prostate Cancer.

We investigated the serum proteome of hormone-sensitive prostate cancer patients to determine candidate biomarkers associated with androgen deprivation therapy (ADT) efficacy. Serum proteomes generated using isobaric mass tags for relative and absolute quantitation were analyzed using reverse-phase liquid chromatography coupled to tandem mass spectrometry. The advanced hormone-sensitive prostate cancer cohorts studied were: (1) untreated "paired" pre-ADT and 4-month post-ADT hormone-sensitive patients (n=15); (2) "early ADT failure" patients (n= 10) in whom ADT treatment failed within a short period of time; and (3) "late ADT failure" patients (n= 10) in whom ADT treatment failed after a prolonged response time. Differential abundance was assessed, and ingenuity pathway analysis (IPA) was used to identify interaction networks in selected candidates from these comparisons. Between "post-ADT" and combined "early" and "late" ADT failure groups 149 differentially detected candidates were observed, and between "early" and "late" ADT failure groups 98 candidates were observed; 47 candidates were common in both comparisons. IPA network enrichment analysis of the 47 candidates identified 3 interaction networks (P< .01) including 17-β-estradiol, nuclear factor kappa-light-chain enhancer of activated B cells complex, and P38 mitogen-activated protein kinases as pathways with potential markers of response to ADT. A global proteomic analysis identified pathways with markers of ADT response, which will need validation in independent data sets.

Cost-effectiveness analysis of abiraterone, docetaxel or placebo plus androgen deprivation therapy for hormone-sensitive advanced prostate cancer.

ABSTRACTObjective To evaluate the cost-effectiveness of the addition of chemotherapy or abiraterone to androgen deprivation.Methods We developed an analytical model to determine the cost-effectiveness of the addition of docetaxel or abiraterone versus androgen deprivation therapy alone. Direct and indirect costs were included in the model. The effects were expressed in Quality-Adjusted Life Years adjusted for side effects.Results Compared to androgen deprivation therapy alone, the addition of chemotherapy and of abiraterone generated 0.492 and 0.999, respectively, in Quality-Adjusted Life Years. Abiraterone led to a Quality-Adjusted Life Years gain of 0.506 compared to docetaxel. The incremental costs per Quality-Adjusted Life Years were R$ 133.649,22 for docetaxel, R$ 330.828,70 for abiraterone and R$ 571.379,42 for abiraterone compared to docetaxel, respectively.Conclusion The addition of chemotherapy to androgen deprivation therapy is more cost-effective than the addition of abiraterone to androgen deprivation therapy. However, discounts on abiraterone cost might improve cost-effectiveness.

Time to progression to castration-resistant prostate cancer after commencing combined androgen blockade for advanced hormone-sensitive prostate cancer.

PurposeThe aim of our retrospective study was to determine the time to progression to castration-resistant prostate cancer (CRPC) in prostate cancer patients who undergo combined androgen blockade (CAB), as well as their prognoses.Materials and MethodsWe examined the overall survival (OS) and disease-specific survival rates, as well as the time to CRPC development, in 387 patients who were treated with CAB for prostate cancer. The disease-specific survival rate and time to CRPC were stratified by prostate-specific antigen (PSA) levels, Gleason score (GS), and presence of metastasis at diagnosis. We designated high-risk patients as those satisfying at least two of the following three criteria: extent of disease of bone metastasis grade ≥2, presence of metastasis at diagnosis, and a GS ≥8.ResultsThe 10- and 15-year OS rates were 74.0% and 50.4%, respectively, while the corresponding disease-specific survival rates were both 86.8%. Metastasis at diagnosis was an independent prognostic factor for disease-specific survival. The median time to CRPC development was 140.7 months. A PSA level ≥20 ng/mL, a GS ≥8, and the presence of metastasis at diagnosis were independent predictors of a shorter time to CRPC development. The 10-year disease-specific survival rate in the high-risk group was significantly lower than that in the low-risk group (approximately 74% vs. 98%), and the time to CRPC development was significantly shorter (median: 20.5 months vs. not reached).ConclusionsThe time to CRPC development was shorter in high-risk prostate cancer patients with metastases. Such patients require alternative novel treatment modalities.

Cardiovascular and Metabolic Effects of Androgen-Deprivation Therapy for Prostate Cancer.

Androgen-deprivation therapy (ADT) entails lowering serum testosterone levels to castrate levels and forms a cornerstone of the management of hormone-sensitive advanced prostate cancer; however, the benefit of ADT is partially offset by its detrimental metabolic and cardiovascular adverse effects. ADT decreases insulin sensitivity while promoting dyslipidemia and sarcopenic obesity, which leads to an increased risk of cardiovascular morbidity and potentially mortality. The risk seems to be highest in elderly patients who have had recent cardiovascular events before starting ADT. It is prudent to engage in an individualized risk-benefit discussion and develop a cohesive multidisciplinary management plan to medically optimize and closely observe these patients before and during treatment with ADT.

Molecular mechanisms of castration-resistant prostate cancer progressed from prostate cancer by androgen deprivation treatment

Androgen deprivation treatment (ADT) is the gold standard of care for patients with locally advanced or metastatic hormone-sensitive prostate cancer. However, most of these patients have developed to the castration-resistant prostate cancer (CRPC) after months or years through a series of different molecular mechanisms during ADT. So far, CRPC is still incurable and deadly, therefore, it is very important for researchers to study different molecular mechanism in the occurrence and development of CRPC, which may provide some new directions for targeted therapy. Key words: Prostatic neoplasms; Receptors, androgen; Carcinoma, neuroendocrine; Neoplastic stem cells; Transformation

Network metanalysis and cost-effectiveness of abiraterone, docetaxel or placebo plus androgen deprivation therapy (ADT) for hormone-sensitive advanced prostate cancer.

6615Background: Prostate cancer is the leading neoplasm among men worldwide. The objective of this study is to evaluate the cost-effectiveness of the addition of chemotherapy or abiraterone to ADT ...

Activity of VERU-111, an novel oral α and β tubulin inhibitor, against paclitaxel sensitive and resistant prostate cancer.

302 Background: Following proven efficiacy of docetaxel against hormone sensitive advanced prostate cancer (CHAARTED and STAMPEDE studies), the use of docetaxel for the treatment of hormone sensitive and castrate resistant metastatic prostate cancer has increased. Unfortunately, the utility of taxanes in prostate cancer has been limited because of the development of resistance, the need for IV infusion, and the associated treatment toxicity. VERU-111 is a highly orally available, novel α and β tubulin inhibitor, developed using a rationale design strategy to bind through hydrogen bonds to the α and β subunits of tubulin. VERU-111 inhibits tubulin polymerization and is not a substrate for multi-drug resistance proteins, a common mechanism for taxane resistance. Methods: In this study, dosing regimens of VERU-111 (oral) were tested in comparison with docetaxel (IV) and a vehicle (oral) in PC3 as well as in paclitaxel resistant PC3 (PC3-TXR). xenograft models. VERU-111 was evaluated at 3.3 mg/kg (5 days/week), 10 mg/kg (3 days/week), 15 mg/kg (2 days per week), 15 mg/kg (3 days per week) and 20 mg/kg (1 day/week). The animals were treated for 28 days and tumor volume and percentage size were calculated. Results: In the parental PC-3 model, animals treated with oral VERU-111, in all of the dose schemes tested, performed statistically indistinguishably from the IV docetaxel administration. In the PC3-TXR model, IV docetaxel had no impact on tumor growth whereas oral VERU-111 resulted in almost complete inhibition of tumor growth at 3.3 mg/kg (5 days/week) and 10 mg/kg (3 days/ week) as well as 20 mg/kg (1 day/week). In early toxicity studies, the animals treated with VERU-111 did not suffer any significant safety signals and gained weight during treatment. Conclusions: VERU-111 is a novel, oral α and β tubulin inhibitor that has drug characteristics making it an ideal candidate to be a therapeutic option for hormone sensitive and castrate resistant advanced prostate cancer. VERU-111 can be administered, with efficacy, as infrequent as once per week and will not require daily dosing. Additional toxicity studies are currently being performed with a Phase 1/2 study being planned to begin later this year.

Darolutamide (ODM-201) for the treatment of prostate cancer

ABSTRACTIntroduction: Androgen deprivation therapy (ADT) is a mainstay initial treatment for advanced hormone-sensitive prostate cancer (HSPC), but disease progression to castration-resistant prostate cancer (CRPC) invariably occurs when patients do not succumb to another disease or comorbidity. Recognition that the androgen receptor (AR) axis continues to drive disease progression has led to the development of several AR-directed approved agents, including abiraterone acetate and enzalutamide. An investigational agent, darolutamide (ODM-201, BAY-1841788), has completed early-phase clinical trials, and two global phase III trials are currently accruing patients.Areas covered: The unmet clinical need, pharmacokinetics, preclinical development, and clinical efficacy and safety of darolutamide for the treatment of advanced prostate cancer are reviewed. The design of two ongoing phase III trials (ARAMIS and ARASENS) of darolutamide in men with non-metastatic CRPC and metastatic HSPC, respectively, are also discussed.Expert opinion: Darolutamide is an oral, investigational, high-affinity AR antagonist which has activity against known AR mutants that confer resistance to other second-generation antiandrogens, has minimal blood–brain barrier penetration, and does not significantly increase serum testosterone. These features may offer potential advantages over the second-generation antiandrogens. In the phase I/II ARADES trial, darolutamide demonstrated promising antitumor activity and a favorable safety profile in men with metastatic CRPC.

Long-term androgen deprivation therapy (ADT) with leuprorelin and quality of life in patients with advanced prostate cancer (PCa).

268 Background: LHRH analogs are the gold standard for treatment of patients with hormone-sensitive advanced PCa. In this study, we investigated the quality of life (QoL) of PCa patients under long-term treatment with leuprorelin acetate in microcapsules (1, 3, and 6 month depot formulation) for up to 19.8 years. Methods: Observational and retrospective analysis of data from 536 PCa patients treated with leuproreline and 116 patients of a control group (CG, ≥ 77 years of age, &gt; 5 years urological treatment, no cancer, no ADT). Data was collected in 30 German office based urological practices using EORTC questionnaires QLQ-C30 and QLQ-PR25. Results: Mean treatment duration was 8.6 years (range: 4.5 - 19.8 years). Mean age ± SD of PCa patients (79.6 ± 6.3 years) was comparable to CG (80.5 ± 3.1 years), as were body height, weight, BMI, and Karnofsky-Index (88.0 ± 12.7 vs. 88.4 ± 12.0). The general health status (QLQ-C30) was comparable for PCa patients vs. CG: 64.6 ± 20.5 vs. 66.8 ± 20.3; p = 0.3117. Marginal differences were observed regarding physical functioning (73.2 ± 23.1 vs. 78.1 ± 21.0; p = 0.0402) and role functioning (70.6 ± 30.4 vs. 74.4 ± 25.7; p = 0.1648). PCa patients rated fatigue (33.6 ± 25.1 vs. 28.8 ± 23.3; p = 0.0629), dyspnoea (24.0 ± 28.5 vs. 19.6 ± 26.9; p = 0.1307), and insomnia (28.9 ± 32.6 vs. 23.7 ± 27.2; p = 0.0751) slightly worse than CG. As assessed by QLQ-PR25, PCa patients scored lower on sexual activity (12.0 ± 20.6 vs. 23.7 ± 25.7; p &lt; 0.0001) and sexual function (43.3 ± 25.8 vs. 55.9 ± 27.0; p = 0.0067) compared to CG. PCa patients had less urinary tract symptoms (28.2 ± 19.8 vs. 31.2 ± 19.2; p = 0.1472) but stronger symptoms of androgen deprivation (21.4 ± 17.3 vs. 10.8 ± 13.2; p &lt; 0.0001), and they had a higher need of incontinence aids (29.6 ± 34.2 vs. 16.7 ± 20.5; p = 0.0056) – however, 136 of the 536 PCa patients had a prostatectomy. Conclusions: In this study, PCa patients treated with leuprorelin for up to 19.8 years (8.6 years on average) had an overall QoL comparable to an age-matched control group. As expected, sexual activity and sexual function were lower in PCa patients under ADT. Overall, treatment with leuprorelin is a well-tolerated long-term therapy for patients with hormone-sensitive advanced PCa. Clinical trial information: ENA E005(a) / DE-N-LEU-019(a).

Options of Chemotherapy in the Treatment of Prostate Cancer

Prostate cancer is one of the most common malignancies in men. Chemotherapy has an important role in the management of prostate cancer, especially for the treatment of castrate resistant prostate cancer (mCRPC). According to recently published studies, chemotherapy can also be used to treat advanced hormone sensitive disease. The aim of this report is to review the currently available options for chemotherapy of prostate cancer. Docetaxel is a chemotherapeutic agent used for standard treatment of mCRPC as 1st line therapy. In TAX 327 and SWOG 9916 studies reported in 2004, docetaxel, the first cytostatic agent indicated for this disease, prolonged overall survival. As a 2nd line mCRPC treatment, kabazitaxel resulted in longer overall survival than mitoxantrone, according to the results of the TROPIC study. Targeted hormone treatment, radium-223 irradiation, and immunotherapy are other treatment options for patients with mCRPC. Currently, the main focus is to develop an optimal sequence of treatments. Standard androgen deprivation therapy (ADT) is the standard option for patients with advanced hormone sensitive prostate cancer. According to recently published studies (CHAARTED, STAMPEDE), docetaxel with ADT increases overall survival in this group of patients. In the Czech Republic, this option is still off-label. Chemotherapy is not indicated in patients with early prostate cancer after radical prostatectomy or radiotherapy.Key words: prostate cancer - metastasis - chemotherapy - docetaxel - cabazitaxelThe authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 9. 5. 2016Accepted: 6. 6. 2016.

Switching from an LHRH Antagonist to an LHRH Agonist: A Case Report of 10 Finnish Patients with Advanced Prostate Cancer.

IntroductionLuteinizing hormone-releasing hormone (LHRH) analogues are widely used for the treatment of advanced hormone-dependent prostate cancer. However, there are currently no clinical guidelines for switching between LHRH analogues. It has been reported that there may be clinical benefits for patients switching between different formulations of LHRH agonists, as well as from an LHRH agonist to LHRH antagonist, but there are no published data on switching from an LHRH antagonist to an LHRH agonist. In this paper, we summarize the clinical notes of 10 patients with hormone-sensitive advanced prostate cancer who switched from an LHRH antagonist to an LHRH agonist.MethodsPatients with T3N0M0–T4N1M1 prostate cancer experiencing injection site reactions, such as pain and swelling, with monthly degarelix (Firmagon®) subcutaneous injections were switched to the 3-monthly leuprorelin acetate implant (Leuprorelin Sandoz®) subcutaneous injections.ResultsMean patient age was 75 years (SD 8.3; range 59–85) and Gleason scores ranged from 7 to 9. The mean [±standard deviation (SD)] duration of degarelix treatment was 5 ± 3.7 months (range 2–13). After switching, prostate serum antigen levels were comparable or reduced from those measured prior to switching, showing that efficacy was not compromised. Throughout the course of treatment, no patients reported injection site reactions. Patients reported increased satisfaction with the leuprorelin acetate implant versus degarelix, mainly because of a lack of injection site reactions and reduced frequency of injection.ConclusionThis is the first report of the clinical experience and potential cost implications of switching from an LHRH antagonist to an LHRH agonist. These data are consistent with other experiences of switching between LHRH analogues in terms of efficacy, safety, and potential cost savings, and provide preliminary evidence that the switch from an LHRH antagonist to an agonist is safe and equally efficacious.

Degarelix for treating advanced hormone-sensitive prostate cancer

Degarelix for treating advanced hormone-sensitive prostate cancer

Androgen deprivation therapy with Leuprolide acetate for treatment of advanced prostate cancer

ABSTRACTIntroduction: Hormone sensitive advanced prostate cancer (PCa) is an incurable disease that is treated with a variety of hormonal therapies targeting the androgen/androgen receptor signaling axis. For decades androgen deprivation therapy (ADT) by surgical or chemical castration is the gold standard for the treatment of advanced PCa.Areas covered: This review discusses the pharmacological features of Leuprolide, a luteinizing hormone-releasing hormone (LHRH) agonists/analog and the most commonly used drug in ADT.Expert opinion: Although Leuprolide has been on the market for more than 30 years it is still the leading option for ADT and serves as a basis for most multimodal therapy concepts. The fact that with the onset of castration-resistance in late stage metastatic disease, a prolongation of ADT in combination with a second line hormonal manipulation is recommended supports the importance of the compound for daily clinical practice.

Association of single nucleotide polymorphism in four genes and response to androgen deprivation therapy (ADT) in men with advanced hormone sensitive prostate cancer (aHSPC).

224 Background: Germline variations in genes involved in androgen biosynthesis and metabolic pathways may predict time to response to androgen deprivation therapy (ADT) in aHSPC, serve as prognostic and predictive biomarkers, and guide towards more individualized upfront therapy. Methods: 706 single nucleotide polymorphisms (SNPs) from the Illumina OmniExpress genotyping platform within the boundaries of 59 genes reported to be involved in the androgen metabolic pathway were investigated for association with time to onset of castration resistance prostate cancer (CRPC) in 171 Caucasian men with aHSPC, i.e. those progressing after definitive treatment (biochemical recurrence alone, or onset of metastatic disease), undergoing treatment with ADT. Cox proportional hazard analysis was employed using Gleason score as a covariate and assessing each SNP under an additive genetic model in which the number of minor alleles contributes increasing risk (or protection). Results: Five SNPs in four genes showed evidence of association with time to CRPC on ADT while controlling for Gleason Score (p &lt; .0002) (Table). Each of these genes had other nearby SNPs with at least nominal (p &lt; 0.05) significance and so, don’t appear to be false positives. Conclusions: Although none of these SNPs exceeded a strict Bonferoni multiple testing correction (p &lt; 0.00007), that threshold is almost certainly conservative as the SNPs and tests are correlated. These results are being validated in a larger cohort and may serve as predictive markers to ADT in this setting. [Table: see text]

Abstract 39: Association of single nucleotide polymorphisms (SNPs) in STS and SULT2B1 and response to androgen deprivation therapy (ADT) in men with advanced hormone sensitive prostate cancer (aHSPC)

Abstract Background: Germline variations in genes involved in androgen biosynthesis and metabolic pathways may predict time to response to androgen deprivation therapy (ADT) in aHSPC, serve as prognostic and predictive biomarkers, and guide towards more individualized upfront therapy. Methods: 795 single nucleotide polymorphisms (SNPs) from the Illumina OmniExpress genotyping platform within the boundaries of 60 genes reported to be involved in the androgen metabolic pathway were investigated for association with time to onset of castration resistance prostate cancer (CRPC) in 118 Caucasian men with aHSPC, i.e. those progressing after definitive treatment, undergoing treatment with ADT. Cox proportional hazard analysis was employed using Gleason score as a covariate and assessing each SNP under an additive genetic model in which the number of minor alleles contributes increasing risk (or protection). Results: Three SNPs in STS (steroid sulfatase gene), and three SNPs in SULT2B1 (sulfotransferase 2B1 gene) were significantly associated with time to CRPC on ADT while controlling for Gleason Score (p &amp;lt; .005). Conclusions: SNPs in STS and SULT2B1 significantly associated with time to CRPC on ADT in aHSPC, and may serve as predictive markers to ADT in this setting. Data are being validated in a larger cohort. Citation Format: Neeraj Agarwal, Tyler Buckley, James Farnham, Shiven B. Patel, Archana Agarwal, Srinivas Tantravahi, Craig Teerlink, Frederick S. Albright, Robert A. Stephenson, Anitha Alex, Lisa Cannon-Albright. Association of single nucleotide polymorphisms (SNPs) in STS and SULT2B1 and response to androgen deprivation therapy (ADT) in men with advanced hormone sensitive prostate cancer (aHSPC). [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr 39.