Degarelix monotherapy compared with luteinizing hormone-releasing hormone (LHRH) agonists plus anti-androgen flare protection in advanced prostate cancer: an analysis of two randomized controlled trials.

OBJECTIVES: The objective of this study was to assess differences in efficacy outcomes between luteinizing hormone-releasing hormone (LHRH) agonist plus antiandrogen (AA) flare protection and monotherapy with the gonadotrophin-releasing hormone antagonist degarelix in patients with prostate cancer. METHODS: Data from 1455 patients were pooled from two prospective, phase III randomized 1-year clinical trials of degarelix versus LHRH agonist with or without AA. The AA bicalutamide was administered at the investigator's discretion. Adjusted hazard ratios (HRs) were calculated using a Cox proportional hazards regression model and a conditional logistic regression model was used for a case-control analysis of odds ratios (ORs). RESULTS: Patients received degarelix monotherapy (n = 972) or LHRH agonist (n = 483) of whom 57 also received AA. Overall, prostate-specific antigen progression-free survival (PSA PFS) was improved with degarelix versus LHRH agonist + AA (Cox proportional hazards regression model-adjusted HR for PSA PFS failure was 0.56 [95% confidence interval (CI) 0.33-0.97, p = 0.038]). To compensate for a higher proportion of patients with metastases, Gleason score 7-10, and PSA >20 ng/ml in the LHRH agonist + AA group, a case-control analysis using a conditional logistic regression model was utilized. This resulted in an OR for PSA PFS of 0.42 (95% CI 0.20-0.89; p = 0.023) in the overall population, and 0.35 (95% CI 0.13-0.96; p = 0.042) in patients with PSA >50 ng/ml at baseline, when treated with degarelix versus LHRH agonists + AA. There were a small number of deaths, 1.9% with degarelix and 7% with LHRH agonists + AA (case-control analysis OR = 0.37; p = 0.085). CONCLUSIONS: Degarelix monotherapy produced a more favorable effect on PSA PFS outcomes than a LHRH agonist + AA flare protection therapy in patients with prostate cancer when a case-control analysis was used to compensate for differences between treatment groups.

Efficacy of degarelix in prostate cancer patients following failure on luteinizing hormone-releasing hormone agonist treatment: results from an open-label, multicentre, uncontrolled, phase II trial (CS27).

OBJECTIVE: To evaluate the efficacy of second-line degarelix in patients with prostate cancer (PCa) after treatment failure with a luteinizing hormone-releasing hormone (LHRH) agonist. METHODS: This 1-year exploratory, multicentre, open-label phase II trial was performed in 2 patient cohorts (Cohort 1, n = 25; Cohort 2, n = 12) in Germany. Patients with castrate-resistant PCa after primary hormonal treatment received degarelix 240 mg, followed by 11 monthly maintenance doses of 80 mg. The primary endpoint was the proportion of patients with decreasing/stable prostate-specific antigen (PSA) (relative change ⩽+10% of baseline PSA) after 3 months. RESULTS: At Month 3, the response rate (intention-to-treat, last observation carried forward analysis) was 16.7% [95% confidence interval (CI): 4.74-37.38] in Cohort 1 and 33.3% (95% CI: 9.92-65.11) in Cohort 2. The probability of completing 12 months without PSA progression was 8.8% (95% CI: 1.51-24.3) in Cohort 1 and 8.3% (95% CI: 0.5-31.1) in Cohort 2. Degarelix was well tolerated; the most frequently reported adverse events were local injection-site reactions. CONCLUSIONS: In PCa patients who failed LHRH therapy, degarelix was well tolerated and achieved a limited PSA response. Phase III trials show that disease control benefits with degarelix versus agonists are more clearly demonstrated as first-line therapy.

Long-term tolerability and efficacy of degarelix: 5-year results from a phase III extension trial with a 1-arm crossover from leuprolide to degarelix.

OBJECTIVE: To demonstrate the safety and efficacy of up to 5 years of degarelix treatment and the effects of crossing over from leuprolide to degarelix in the extension phase of a phase III pivotal 1-year trial. METHODS: Patients receiving degarelix who completed the 1-year trial continued on 80 mg (n = 125) or 160 mg (n = 126) maintenance doses. Patients who received leuprolide were rerandomized to degarelix 240/80 mg (n = 69) or 240/160 mg (n = 65). Safety and tolerability were assessed (primary end point), as well as testosterone and prostate-specific antigen levels and prostate-specific antigen progression-free survival (secondary end points). RESULTS: Adverse event frequency was similar between both the groups. Adverse events included initial injection site reactions, hot flushes, and increased weight. Testosterone and prostate-specific antigen values during the extension study were similar to those seen during the 1-year trial in patients who continued on degarelix or crossed over from leuprolide. The prostate-specific antigen progression-free survival hazard rate was decreased significantly after the crossover in the leuprolide to degarelix group (from 0.20 to 0.09; P = .002), whereas in patients who continued on degarelix, the rate did not change significantly. In patients with baseline prostate-specific antigen >20 ng/mL, the same hazard rate change pattern was observed on crossover (from 0.38 to 0.19; P = .019). CONCLUSION: Degarelix was well tolerated; no safety concerns were identified. The significant prostate-specific antigen progression-free survival benefit established for degarelix over leuprolide during year 1 remained consistent at 5 years.

Disease control outcomes from analysis of pooled individual patient data from five comparative randomised clinical trials of degarelix versus luteinising hormone-releasing hormone agonists.

BACKGROUND: Studies comparing the gonadotropin-releasing hormone antagonist, degarelix, with luteinising hormone-releasing hormone (LHRH) agonists indicate differences in outcomes. OBJECTIVE: To assess differences in efficacy and safety outcomes in a pooled analysis of trials comparing degarelix with LHRH agonists. DESIGN, SETTING, AND PARTICIPANTS: Data were pooled from five prospective, phase 3 or 3b randomised trials (n=1925) of degarelix and leuprolide or goserelin in men requiring androgen deprivation therapy for the treatment of prostate cancer. Patients received either 3 mo (n=467) or 12 mo (n=1458) of treatment. INTERVENTION: Men were randomised to receive degarelix (n=1266), leuprolide (n=201), or goserelin (n=458). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Unadjusted Kaplan-Meier analyses were supported by the Cox proportional hazards model, adjusted for disease-related baseline factors, to estimate hazard ratios (HRs) of efficacy and safety outcomes. The Fisher exact test compared crude incidences of adverse events. RESULTS AND LIMITATIONS: Prostate-specific antigen (PSA) progression-free survival (PFS) was improved in the degarelix group (HR: 0.71; p=0.017). For patients with baseline PSA levels >20 ng/ml, the HR for PSA PFS was 0.74 (p=0.052). Overall survival (OS) was higher in the degarelix group (HR: 0.47; p=0.023). OS was particularly improved with degarelix in patients with baseline testosterone levels >2 ng/ml (HR: 0.36; p=0.006). In terms of disease-related adverse events, there were, overall, fewer joint-related signs and symptoms, musculoskeletal events, and urinary tract events in the degarelix group. CONCLUSIONS: These data indicate clinical benefits with degarelix, including a significant improvement in PSA PFS and OS, as well as reduced incidence of joint, musculoskeletal, and urinary tract adverse events, compared with LHRH agonists.

Degarelix versus goserelin (+ antiandrogen flare protection) in the relief of lower urinary tract symptoms secondary to prostate cancer: results from a phase IIIb study (NCT00831233).

INTRODUCTION: No studies to date have assessed the efficacy/tolerability of degarelix in the relief of lower urinary tract symptoms (LUTS) secondary to prostate cancer (PrCa). METHODS: Patients were randomised to degarelix 240/80 mg or goserelin 3.6 mg + bicalutamide flare protection (G+B); both treatments were administered for 3 months. The primary endpoint was change in International Prostate Symptom Score (IPSS) at week 12 compared with baseline. RESULTS: This study was stopped early due to recruitment difficulties. 40 patients received treatment (degarelix n = 27; G+B n = 13); most had locally advanced disease and were highly symptomatic. Degarelix was non-inferior to G+B in reducing IPSS at week 12 in the full analysis set (p = 0.20); the significantly larger IPSS reduction in the per-protocol analysis (p = 0.04) was suggestive of superior reductions with degarelix. Significantly more degarelix patients had improved quality of life (IPSS question) at week 12 (85 vs. 46%; p = 0.01). Mean prostate size reductions at week 12 were 42 versus 25% for patients receiving degarelix versus G+B, respectively (p = 0.04; post hoc analysis). Most adverse events were mild/moderate; more degarelix patients experienced injection site reactions whereas more G+B patients had urinary tract infections/cystitis. CONCLUSION: In 40 men with predominantly locally advanced PrCa and highly symptomatic LUTS, degarelix was at least non-inferior to G+B in reducing IPSS at week 12.

The effect of baseline testosterone on the efficacy of degarelix and leuprolide: further insights from a 12-month, comparative, phase III study in prostate cancer patients.

OBJECTIVE: To investigate the effects of baseline testosterone on testosterone control and prostate-specific antigen (PSA) suppression using data from a phase III trial (CS21) comparing degarelix and leuprolide in prostate cancer. METHODS: In CS21, patients with histologically confirmed prostate cancer (all stages) were randomized to degarelix 240 mg for 1 month followed by monthly maintenance doses of 80 or 160 mg, or leuprolide 7.5 mg/month. Patients receiving leuprolide could receive antiandrogens for flare protection. Treatment effects on testosterone and PSA reduction, testosterone surge, and microsurges were investigated in 3 baseline testosterone subgroups: <3.5, 3.5-5.0, and >5.0 ng/mL. Data are presented for the groups receiving degarelix 240/80 mg (the approved dose) and leuprolide 7.5 mg. RESULTS: Higher baseline testosterone delayed castration with both treatments. However, castrate testosterone levels and PSA suppression occurred more rapidly with degarelix irrespective of baseline testosterone. With leuprolide, the magnitude of testosterone surge and microsurges increased with increasing baseline testosterone. There was no overall correlation between baseline testosterone and initial PSA decrease in either treatment group, although PSA suppression tended to be slowest with leuprolide and fastest with degarelix in the high baseline testosterone subgroup. CONCLUSION: Patients with high baseline testosterone may have greater risk of tumor stimulation (clinical flare) and mini-flares during gonadotrophin-releasing hormone agonist treatment and so the need for flare protection with antiandrogens in these patients is obvious, especially in metastatic disease. Although higher baseline testosterone delays castration, castrate testosterone and PSA suppression occur more rapidly with degarelix, irrespective of baseline testosterone, without the need for flare protection.

An update on the use of gonadotropin-releasing hormone antagonists in prostate cancer.

Androgen deprivation therapy (ADT) is the main treatment approach in advanced prostate cancer and in recent years has primarily involved the use of gonadotropin-releasing hormone (GnRH) agonists. However, despite their efficacy, GnRH agonists have several drawbacks associated with their mode of action. These include an initial testosterone surge and testosterone microsurges on repeat administration. GnRH antagonists provide an alternative approach to ADT with a more direct mode of action that involves immediate blockade of GnRH receptors. Antagonists produce a more rapid suppression of testosterone (and prostate-specific antigen [PSA]) without a testosterone surge or microsurges and appear to offer an effective and well tolerated option for the hormonal treatment of prostate cancer. Comparisons with GnRH agonists have shown GnRH antagonists to be at least as effective in achieving and maintaining castrate testosterone levels in patients with prostate cancer. Furthermore, with antagonists, the lack of an initial testosterone surge (which may cause clinical flare) may allow more rapid relief of symptoms related to prostate cancer, avoid the need for concomitant antiandrogens to prevent clinical flare (so avoiding any antiandrogen-associated adverse events) and allow GnRH antagonist use in patients with high tumour burden and/or acute problems such as spinal cord compression. Although several antagonists have been investigated, only degarelix and abarelix are currently available for clinical use in prostate cancer. Currently, degarelix is the most extensively studied and widely available agent in this class. Degarelix is one of a newer generation of antagonists which, in a comprehensive and ongoing clinical development programme, has been shown to provide rapid, profound and sustained testosterone suppression without the systemic allergic reactions associated with earlier antagonists. This review examines the currently available data on GnRH antagonists in prostate cancer.

A phase III extension trial with a 1-arm crossover from leuprolide to degarelix: comparison of gonadotropin-releasing hormone agonist and antagonist effect on prostate cancer.

PURPOSE: We investigated the efficacy and safety of degarelix treatment and the effects of switching from leuprolide to degarelix in an ongoing extension study with a median 27.5-month followup of a pivotal 1-year prostate cancer trial. MATERIALS AND METHODS: Patients who completed a 1-year pivotal phase III trial continued on the same monthly degarelix maintenance dose (160 or 80 mg in 125 each), or were re-randomized from leuprolide 7.5 mg to degarelix 240/80 mg (69) or 240/160 mg (65). Data are shown on the approved degarelix 240/80 mg dose. The primary end point was safety/tolerability and the secondary end points were testosterone, prostate specific antigen, luteinizing hormone and follicle-stimulating hormone responses, and prostate specific antigen failure and progression-free survival. RESULTS: During followup testosterone and prostate specific antigen suppression were similar to those in the 1-year trial in patients who continued on degarelix or switched from leuprolide. The prostate specific antigen progression-free survival hazard rate was decreased significantly after the switch in the leuprolide/degarelix group while the rate in those who continued on degarelix was consistent with the rate in treatment year 1. The same hazard rate change pattern occurred in the group with baseline prostate specific antigen greater than 20 ng/ml. Adverse event frequency was similar between the groups and decreased with time. CONCLUSIONS: Data support the statistically significant prostate specific antigen progression-free survival benefit for degarelix over leuprolide seen during year 1 and the use of degarelix as first line androgen deprivation therapy as an alternative to a gonadotropin-releasing hormone agonist.

Cardiovascular safety of degarelix: results from a 12-month, comparative, randomized, open label, parallel group phase III trial in patients with prostate cancer.

PURPOSE: We assessed the cardiovascular safety profile of degarelix, a new gonadotropin-releasing hormone antagonist. MATERIALS AND METHODS: This is the first report to our knowledge on cardiovascular safety data from a completed 1-year randomized controlled trial of leuprolide acetate vs degarelix. Outcomes considered in these analyses included the QT interval by central reading and analysis, and cardiovascular adverse events. On multivariate analyses relationships between selected baseline factors and cardiovascular events were evaluated. RESULTS: There were no significant differences between treatment groups for mean change in Fridericia's correction of QT during the trial. Markedly abnormal Fridericia's correction of QT values (500 milliseconds or greater) were observed in only a small number of subjects by treatment group, that is 2 (less than 1%) in the pooled degarelix group and 2 (1%) in the leuprolide group. Supraventricular arrhythmias were the most common type of arrhythmias, affecting 2% of subjects in the pooled degarelix group and 4% in the leuprolide group. Other arrhythmias occurred in 1% or less of subjects by treatment group. The most frequently reported cardiac disorder was ischemic heart disease, which occurred in 4% of subjects treated with degarelix and 10% of those on leuprolide. Cox proportional hazard ratio estimates for selected baseline covariates showed a significantly increased risk of cardiovascular events by age (p=0.0459) and systolic blood pressure (p=0.0061). CONCLUSIONS: In men with prostate cancer degarelix and leuprolide have similar cardiovascular safety profiles. These observations suggest that the cardiovascular events associated with both agents result from hypogonadism rather than a direct drug effect.

Additional analysis of the secondary end point of biochemical recurrence rate in a phase 3 trial (CS21) comparing degarelix 80 mg versus leuprolide in prostate cancer patients segmented by baseline characteristics.

BACKGROUND: Recent data suggest prostate-specific antigen (PSA) progression may predict overall survival in prostate cancer patients. OBJECTIVE: To compare the activity of degarelix and leuprolide regarding PSA recurrence-free survival. DESIGN, SETTING, AND PARTICIPANTS: Phase 3, 1-yr, multicentre, randomised, open-label trial comparing the efficacy and safety of degarelix at 240 mg for 1 mo, and then 80 mg monthly (240/80 mg); degarelix at 240 mg for 1 mo, and then 160 mg monthly; and leuprolide at 7.5 mg/mo. Overall, 610 patients with histologically confirmed prostate cancer (all stages), for whom androgen deprivation therapy was indicated, were included. The primary end point of this trial has been reported previously; the protocolled and exploratory subgroup analyses reported in this paper focus on degarelix at 240/80 mg (dose approved by the US Food and Drug Administration and the European Medicine Evaluation Association for the treatment of patients with hormone-naive advanced prostate cancer). MEASUREMENTS: PSA progression-free survival (two consecutive increases in PSA of 50% compared with nadir and ≥ 5 ng/ml on two consecutive measurements at least 2 wk apart or death) and change in PSA were reviewed. Effects of baseline disease stage (localised, locally advanced, and metastatic) and PSA level (<10, 10-20, >20-50, and >50 ng/ml) were analysed. RESULTS AND LIMITATIONS: Patients receiving degarelix showed a significantly lower risk of PSA progression or death compared with leuprolide (p=0.05). PSA recurrences occurred mainly in patients with advanced disease and exclusively in those with baseline PSA >20 ng/ml. Patients with PSA >20 ng/ml had a significantly longer time to PSA recurrence with degarelix (p=0.04). The relatively low number of patients in each subgroup is a limitation of this study. CONCLUSIONS: These results generate the hypothesis that degarelix at 240/80 mg offers improved PSA control compared with leuprolide. PSA recurrences occurred almost exclusively in patients with metastatic prostate cancer or high baseline PSA during this 1-yr study. Further studies are warranted to confirm these findings.

Changes in alkaline phosphatase levels in patients with prostate cancer receiving degarelix or leuprolide: results from a 12-month, comparative, phase III study.

Study Type - Therapy (RCT) Level of Evidence 1b OBJECTIVE To compare the activity of degarelix, a new gonadotrophin-releasing hormone (GnRH) blocker, with leuprolide depot 7.5 mg in the control of total serum alkaline phosphatase (S-ALP) levels in patients with prostate cancer. PATIENTS AND METHODS In the randomized, phase III trial (CS21), patients with histologically confirmed prostate cancer (all stages), were randomized to one of three regimens: degarelix subcutaneous 240 mg for 1 month followed by monthly maintenance doses of 80 mg or 160 mg, or intramuscular leuprolide 7.5 mg/month. Patients receiving leuprolide could also receive antiandrogens for flare protection. We report exploratory S-ALP analyses from CS21, focusing on the comparison of degarelix 240/80 mg with leuprolide 7.5 mg, in line with the recent approvals of this dose by the USA Food and Drug Administration and the European Medicines Agency. RESULTS Overall, 610 patients were included, with a median age of 73 years and median prostate-specific antigen (PSA) level of 19.0 ng/mL. Baseline S-ALP levels were high in metastatic patients and highest in patients with metastatic disease and a haemoglobin level of <13 g/dL. In metastatic disease, after initial peaks in both groups, S-ALP levels were suppressed below baseline with degarelix but were maintained around baseline with leuprolide. The late rise in S-ALP seen with leuprolide was not apparent with degarelix. The pattern of S-ALP response was similar in patients with a baseline PSA level of > or =50 ng/mL. Between-treatment differences in patients with metastatic disease and those with a PSA level of > or =50 ng/mL were significant at day 364 (P = 0.014 and 0.007, respectively). CONCLUSION Patients with metastatic disease or those with PSA levels of > or =50 ng/mL at baseline had greater reductions in S-ALP levels with degarelix than with leuprolide. Patients in the degarelix group maintained S-ALP suppression throughout the study, in contrast to those in the leuprolide group. This suggests that degarelix might offer better S-ALP control than leuprolide and might prolong control of skeletal metastases, compared with GnRH agonists, over a 1-year treatment period.

Degarelix 240/80 mg: a new treatment option for patients with advanced prostate cancer.

Gonadotrophin-releasing hormone (GnRH) receptor blockers (antagonists) are the latest addition to the hormonal therapy armamentarium for patients with prostate cancer. In contrast to the GnRH agonists, GnRH blockers have an immediate onset of action and do not cause an initial surge in testosterone levels that can lead to clinical flare in patients with advanced disease. Degarelix (Firmagon is a new GnRH blocker that has recently been approved by the EMEA and US FDA for the treatment of men with hormone-sensitive advanced prostate cancer. In this article, we briefly review the Phase III trial data for degarelix 240/80 mg (licensed dose) versus leuprolide 7.5 mg that led to these recent approvals.

Degarelix: a new approach for the treatment of prostate cancer.

Androgen deprivation therapy remains the mainstay of medical treatment for prostate cancer. Generally, this is achieved with medical androgen deprivation rather than orchidectomy, as most patients find the permanency and psychological effects of the latter unacceptable. Gonadotrophin-releasing hormone (GnRH) agonists are the most widely used androgen deprivation therapy, but do have some drawbacks. The most apparent is the induction of a transient surge in serum testosterone that may stimulate tumor growth, causing patients to experience new or worsening cancer symptoms. These may include increased bone pain and urinary retention, and consequently delay the therapeutic benefit of these agents. These shortcomings led to the development of the GnRH antagonists/receptor blockers. Degarelix is a novel GnRH receptor blocker that has an immediate onset of action, producing a rapid decrease in luteinizing hormone and follicle-stimulating hormone leading to fast testosterone suppression without the initial surge associated with the GnRH agonists. Administration of subcutaneous degarelix depot has been investigated in multicenter, open-label, randomized, phase II trials of up to 1 year's duration in patients with prostate cancer. Degarelix induced rapid luteinizing hormone suppression and fast, profound and sustained suppression of serum testosterone (or=2 weeks before clinically relevant changes were induced by the GnRH agonist leuprolide. Degarelix was as effective as leuprolide at reducing testosterone

Will GnRH antagonists improve prostate cancer treatment?

Androgen ablation forms a basis for treating prostate cancer and is achieved either by surgical castration, or pharmacologically using oestrogens, anti-androgens and/or gonadotropin-releasing hormone (GnRH) analogues. GnRH antagonists (or blockers) offer a new means of treatment by directly blocking GnRH receptors. Advantages of GnRH antagonists include lack of the initial stimulation of gonadotropin and testosterone production, lack of gonadotropin microsurges and sustained follicle-stimulating hormone suppression; disadvantages include increased histamine release. This review discusses advantages and disadvantages of the GnRH antagonists currently in development, in light of receptor physiology and pre-clinical and clinical data. Comparative clinical trials will ultimately establish their efficacy in comparison to other pharmacotherapies. Therefore, continuing development and refinement is needed to improve prostate cancer treatment.

The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer.

OBJECTIVE: To evaluate the efficacy and safety of degarelix, a new gonadotrophin-releasing hormone (GnRH) antagonist (blocker), vs leuprolide for achieving and maintaining testosterone suppression in a 1-year phase III trial involving patients with prostate cancer. PATIENTS AND METHODS: In all, 610 patients with adenocarcinoma of the prostate (any stage; median age 72 years; median testosterone 3.93 ng/mL, median prostate-specific antigen, PSA, level 19.0 ng/mL) were randomized and received study treatment. Androgen-deprivation therapy was indicated (neoadjuvant hormonal treatment was excluded) according to the investigator's assessment. Three dosing regimens were evaluated: a starting dose of 240 mg of degarelix subcutaneous (s.c.) for 1 month, followed by s.c. maintenance doses of 80 mg or 160 mg monthly, or intramuscular (i.m.) leuprolide doses of 7.5 mg monthly. Therapy was maintained for the 12-month study. Both the intent-to-treat (ITT) and per protocol populations were analysed. RESULTS: The primary endpoint of the trial was suppression of testosterone to

A 1-year, open label, randomized phase II dose finding study of degarelix for the treatment of prostate cancer in North America.

PURPOSE: Degarelix is a gonadotropin-releasing hormone receptor antagonist (blocker) with rapid onset of action suppressing gonadotropins, testosterone and prostate specific antigen in prostate cancer. In the present open label, randomized study in North America we evaluated the efficacy and safety of a starting dose of 200 mg degarelix followed by monthly injections of 60 or 80 mg during 1 year of prostate cancer treatment. MATERIALS AND METHODS: A total of 127 patients (median age 76 years, range 47 to 93) with histologically confirmed prostate cancer were enrolled in the study. Efficacy was assessed by measuring serum testosterone and prostate specific antigen. RESULTS: Median baseline testosterone and prostate specific antigen levels were 4.13 ng/ml (P25-P75 3.03-5.11) and 13.4 ng/ml (P25-P75 6.80-25.7), respectively. The starting dose induced a rapid suppression of testosterone in that 88% of the patients had testosterone levels of 0.5 ng/ml or less 1 month after the injection. For patients who had testosterone levels of 0.5 ng/ml or less after 1 month, 93% and 98% of those receiving maintenance doses of 60 and 80 mg, respectively, had testosterone levels that were consistently 0.5 ng/ml or less at all monthly measurements from 1 month to 1 year. No evidence of testosterone surge was detected. In both groups prostate specific antigen decreased by 96% after 1 year and median time to 90% reduction in prostate specific antigen was 56 days. Six patients (5%) withdrew from the study due to adverse events. CONCLUSIONS: Degarelix treatment for 1 year resulted in a fast, profound and sustained suppression of testosterone and prostate specific antigen with no evidence of testosterone surge. Degarelix was well tolerated.