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Boeric Persson - One of the best experts on this subject based on the ideXlab platform.
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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
2014Co-Authors: David E Crawford, Neal D Shore, Fritz H Schroder, Bertrand Tombal, Kurt Miller, Laurent Boccongibod, Judd W Moul, Tine Kold Olesen, Anders Malmberg, Boeric PerssonAbstract: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.
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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
2012Co-Authors: Janerik Damber, Laurent Boccongibod, Tine Kold Olesen, Teuvo L J Tammela, Peter Iversen, Peranders Abrahamsson, Egbert Van Der Meulen, Boeric PerssonAbstract: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: 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.
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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
2011Co-Authors: David E Crawford, Neal D Shore, Fritz H Schroder, Bertrand Tombal, Kurt Miller, Laurent Boccongibod, Judd W Moul, Tine Kold Olesen, Jenskristian Jensen, Boeric PerssonAbstract: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.
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changes in alkaline phosphatase levels in patients with prostate cancer receiving degarelix or Leuprolide results from a 12 month comparative phase iii study
2009Co-Authors: Fritz H Schroder, Neal D Shore, Bertrand Tombal, Kurt Miller, Laurent Boccongibod, David E Crawford, Judd W Moul, Tine Kold Olesen, Boeric PerssonAbstract: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 = 50 ng/mL. Between-treatment differences in patients with metastatic disease and those with a PSA level of >= 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 >= 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.
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changes in alkaline phosphatase levels in patients with prostate cancer receiving degarelix or Leuprolide results from a 12 month comparative phase iii study
2009Co-Authors: Fritz H Schroder, Neal D Shore, Bertrand Tombal, Kurt Miller, Laurent Boccongibod, David E Crawford, Judd W Moul, Tine Kold Olesen, Boeric PerssonAbstract: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 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.
David E Crawford - One of the best experts on this subject based on the ideXlab platform.
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impact of late dosing on testosterone suppression with 2 different Leuprolide acetate formulations in situ gel and microsphere an analysis of united states clinical data
2021Co-Authors: David E Crawford, Thomas E Keane, Judd W Moul, Jason Hafron, Scott T Tagawa, Przemyslaw Twardowski, Richard G Harris, Raoul S Concepcion, C S Higano, Lucio N GordanAbstract:Purpose:Nonadherence to dosing schedules for androgen deprivation therapy increases the risk of testosterone escape for patients with prostate cancer. Two approved formulations of Leuprolide acetat...
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FSH suppression and tumour control in patients with prostate cancer during androgen deprivation with a GnRH agonist or antagonist
2019Co-Authors: David E Crawford, B. Tombal, T. Keane, F. Boccardo, K. Miller, N. Shore, J. W. Moul, J.-e. Damber, L. Collette, B.-e. PerssonAbstract:Background: Gonadotropin releasing hormone (GnRH) antagonists suppress follicle-stimulating hormone (FSH) to lower levels than GnRH agonists. This may partially explain the differences between these agents on prostate cancer outcomes. In this post-hoc analysis, FSH and prostate specific antigen (PSA) responses and the impact of cross-over from Leuprolide to degarelix were evaluated from a 1-year comparative study (CS21) and its extension study (CS21A). Materials and methods: Overall, 610 patients were enrolled in CS21, wherein PSA and FSH levels were evaluated monthly. CS21A evaluated 386 patients, including those previously treated with degarelix (n = 251) who continued to receive degarelix, and those previously treated with Leuprolide (n = 135) who crossed-over to receive degarelix. PSA and FSH levels were evaluated in CS21A for 3 months after cross-over. The associations between measurements were assessed using Spearman’s correlation coefficient. The impact of class variables on FSH suppression were evaluated using Analysis of Variance. Results: Rapid PSA and FSH suppression was observed and maintained in the degarelix arm (CS21 and CS21A), while patients on Leuprolide experienced rising PSA during CS21. Patients crossed-over from Leuprolide to degarelix achieved a suppression of FSH and a significant PSA decrease. PSA and FSH levels were significantly (p
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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
2014Co-Authors: David E Crawford, Neal D Shore, Fritz H Schroder, Bertrand Tombal, Kurt Miller, Laurent Boccongibod, Judd W Moul, Tine Kold Olesen, Anders Malmberg, Boeric PerssonAbstract: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.
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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
2011Co-Authors: David E Crawford, Neal D Shore, Fritz H Schroder, Bertrand Tombal, Kurt Miller, Laurent Boccongibod, Judd W Moul, Tine Kold Olesen, Jenskristian Jensen, Boeric PerssonAbstract: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.
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changes in alkaline phosphatase levels in patients with prostate cancer receiving degarelix or Leuprolide results from a 12 month comparative phase iii study
2009Co-Authors: Fritz H Schroder, Neal D Shore, Bertrand Tombal, Kurt Miller, Laurent Boccongibod, David E Crawford, Judd W Moul, Tine Kold Olesen, Boeric PerssonAbstract: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 = 50 ng/mL. Between-treatment differences in patients with metastatic disease and those with a PSA level of >= 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 >= 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.
Neal D Shore - One of the best experts on this subject based on the ideXlab platform.
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impact of age on efficacy and safety of relugolix a subgroup analysis from the randomized phase 3 hero study versus Leuprolide in men with advanced prostate cancer
2021Co-Authors: Michael S Cookson, Neal D Shore, Daniel J George, Daniel Saltzstein, Ronald Tutrone, Hideyuki Akaza, Alberto Bossi, Bryan Selby, Bruce P Brown, Jacqueline M WallingAbstract:5075Background: In the phase 3 HERO study, the oral GnRH receptor antagonist relugolix demonstrated sustained testosterone suppression superior to that of Leuprolide and a comparative 54% decrease ...
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oral relugolix for androgen deprivation therapy in advanced prostate cancer
2020Co-Authors: Neal D Shore, Fred Saad, Michael S Cookson, Daniel J George, Daniel Saltzstein, Ronald Tutrone, Hideyuki Akaza, Alberto Bossi, David Van Veenhuyzen, Bryan SelbyAbstract:Abstract Background Injectable luteinizing hormone–releasing hormone agonists (e.g., Leuprolide) are the standard agents for achieving androgen deprivation for prostate cancer despite the initial t...
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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
2014Co-Authors: David E Crawford, Neal D Shore, Fritz H Schroder, Bertrand Tombal, Kurt Miller, Laurent Boccongibod, Judd W Moul, Tine Kold Olesen, Anders Malmberg, Boeric PerssonAbstract: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.
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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
2011Co-Authors: David E Crawford, Neal D Shore, Fritz H Schroder, Bertrand Tombal, Kurt Miller, Laurent Boccongibod, Judd W Moul, Tine Kold Olesen, Jenskristian Jensen, Boeric PerssonAbstract: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.
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changes in alkaline phosphatase levels in patients with prostate cancer receiving degarelix or Leuprolide results from a 12 month comparative phase iii study
2009Co-Authors: Fritz H Schroder, Neal D Shore, Bertrand Tombal, Kurt Miller, Laurent Boccongibod, David E Crawford, Judd W Moul, Tine Kold Olesen, Boeric PerssonAbstract: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 = 50 ng/mL. Between-treatment differences in patients with metastatic disease and those with a PSA level of >= 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 >= 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.
Agneta Bergqvist - One of the best experts on this subject based on the ideXlab platform.
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subcutaneous depot medroxyprogesterone acetate versus Leuprolide acetate in the treatment of endometriosis associated pain
2006Co-Authors: P G Crosignani, Anthony A. Luciano, Amrit Ray, Agneta BergqvistAbstract:This study compared the effectiveness and safety of a new subcutaneous formulation of depot medroxyprogesterone acetate delivering 104 mg per 0.65 mL (DMPA-SC 104) every 3 months with those of Leuprolide-a widely used and effective treatment for pain from endometriosis-in a dose of 3.75 mg per month (or 11.25 mg every 3 months). Bone mineral density (BMD) was estimated after 6 months of treatment and again at a 12-month follow-up assessment. Clinical end points included dysmenorrhea, dyspareunia, pelvic pain and tenderness, and induration. In addition, productivity was monitored at 6 and 18 months. Both treatments began in the first 5 days of a normal menstrual cycle. Participants were 299 women with laparoscopically diagnosed endometriosis; 153 were randomized to receive DMPA-SC 104, and 146 Leuprolide. Between two thirds and three fourths of patients in both groups completed 12 months of follow up. The 2 treatment groups were initially similar in nearly all respects. All signs and symptoms of endometriosis were lessened as effectively by treatment with DMPA-SC 104 as with Leuprolide. More than three fourths of patients in each treatment group maintained improvement at 12 months. Patients reported a higher quality of life with either treatment, and those in both treatment groups were satisfied with their results. Productivity also improved significantly in both groups. Patients taking Leuprolide had significant reductions from baseline BMD in the total hip and lumbar spine regions after 6 months of treatment. A similar change occurred, in the spine only, in patients given DMPA-SC 104. At 12 months, BMD values were normal at both sites in the latter group, whereas women treated with Leuprolide continued to have declining values at both sites. Hot flushes were less frequent in the DMPA-SC 104 group as was amenorrhea. Serious adverse events occurred in 4% of the DMPA-SC 104 group and 2% of patients given Leuprolide. The most common side effect during follow-up was breast pain, which was slightly more frequent in the DMPA-SC 104 group. There were no clinically important changes in hematologic values, biochemical assays, or urinalysis. Although further long-term trials will be needed, the present findings suggest that DMPA-SC 104 may be suitable as a first-line treatment for women having pain caused by endometriosis. (Several investigators, including my colleagues and I.
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Subcutaneous injection of depot medroxyprogesterone acetate compared with Leuprolide acetate in the treatment of endometriosis-associated pain
2006Co-Authors: William D. Schlaff, Sandra A. Carson, Anthony A. Luciano, Doug Ross, Agneta BergqvistAbstract:Objective To compare the efficacy and safety of SC depot medroxyprogesterone acetate (DMPA-SC 104) with that of Leuprolide acetate in treatment of endometriosis. Design Phase 3, multicenter, randomized, evaluator-blinded, comparator-controlled trial. Setting Clinical trial sites in Canada and United States. Patient(s) Two hundred seventy-four women with surgically diagnosed endometriosis. Intervention(s) Intramuscular injections of DMPA-SC (104 mg) or Leuprolide acetate (11.25 mg), given every 3 months for 6 months, with 12 months of posttreatment follow-up. Main Outcome Measure(s) Reduction in five endometriosis symptoms or signs (dysmenorrhea, dyspareunia, pelvic pain, pelvic tenderness, pelvic induration); change in bone mineral density (BMD), hypoestrogenic symptoms, bleeding, and weight. Result(s) The depot medroxyprogesterone acetate given SC was statistically equivalent to Leuprolide in reducing four of five endometriosis symptoms or signs at the end of treatment (month 6) and in reducing all five symptoms after 12 months' follow-up (month 18). Patients in the DMPA-SC 104 group showed significantly less BMD loss than did Leuprolide patients at month 6, with scores returning to baseline at 12 months' follow-up. No statistically significant differences in median weight changes were observed between groups. Compared with Leuprolide, DMPA-SC 104 was associated with fewer hypoestrogenic symptoms but more irregular bleeding. Conclusion(s) Efficacy of DMPA-SC 104 was equivalent to that of Leuprolide for reducing endometriosis-associated pain, with less impact on BMD and fewer hypoestrogenic side effects but more bleeding.
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subcutaneous depot medroxyprogesterone acetate versus Leuprolide acetate in the treatment of endometriosis associated pain
2006Co-Authors: P G Crosignani, Anthony A. Luciano, Amrit Ray, Agneta BergqvistAbstract:BACKGROUND A clinical study compared efficacy and safety of depot medroxyprogesterone acetate (DMPA) with Leuprolide for endometriosis-associated pain. METHODS This multicentre, 18 month, evaluator-blinded, comparator-controlled trial randomized 300 women with laparoscopically diagnosed endometriosis to 6 month treatment with subcutaneous injection of 104 mg/0.65 ml DMPA (DMPA-SC 104) every 3 months or Leuprolide (3.75 mg monthly or 11.25 mg every 3 months), with 12 months post-treatment follow-up. Endpoints included patient response to treatment in five signs/symptoms (dysmenorrhoea, dyspareunia, pelvic pain, pelvic tenderness, induration) and changes in bone mineral density (BMD) and productivity at 6 and 18 months. RESULTS DMPA-SC 104 and Leuprolide produced equivalent (P < 0.02) reductions in at least four pain categories and significant (P < 0.001) improvements in composite score at months 6 and 18. At month 6, reductions in total hip and lumbar spine BMD were significantly less (P < 0.001) with DMPA-SC 104 versus Leuprolide. BMD returned to pre-treatment levels 12 months post-treatment in the DMPA-SC 104 but not the Leuprolide group. Total productivity also significantly (P < or = 0.05) improved in both groups at 6 and 18 months. CONCLUSIONS DMPA-SC 104 reduces endometriosis-associated pain as effectively as Leuprolide and improves productivity with significantly less BMD decline.
Judd W Moul - One of the best experts on this subject based on the ideXlab platform.
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impact of late dosing on testosterone suppression with 2 different Leuprolide acetate formulations in situ gel and microsphere an analysis of united states clinical data
2021Co-Authors: David E Crawford, Thomas E Keane, Judd W Moul, Jason Hafron, Scott T Tagawa, Przemyslaw Twardowski, Richard G Harris, Raoul S Concepcion, C S Higano, Lucio N GordanAbstract:Purpose:Nonadherence to dosing schedules for androgen deprivation therapy increases the risk of testosterone escape for patients with prostate cancer. Two approved formulations of Leuprolide acetat...
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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
2014Co-Authors: David E Crawford, Neal D Shore, Fritz H Schroder, Bertrand Tombal, Kurt Miller, Laurent Boccongibod, Judd W Moul, Tine Kold Olesen, Anders Malmberg, Boeric PerssonAbstract: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.
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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
2011Co-Authors: David E Crawford, Neal D Shore, Fritz H Schroder, Bertrand Tombal, Kurt Miller, Laurent Boccongibod, Judd W Moul, Tine Kold Olesen, Jenskristian Jensen, Boeric PerssonAbstract: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.
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changes in alkaline phosphatase levels in patients with prostate cancer receiving degarelix or Leuprolide results from a 12 month comparative phase iii study
2009Co-Authors: Fritz H Schroder, Neal D Shore, Bertrand Tombal, Kurt Miller, Laurent Boccongibod, David E Crawford, Judd W Moul, Tine Kold Olesen, Boeric PerssonAbstract: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 = 50 ng/mL. Between-treatment differences in patients with metastatic disease and those with a PSA level of >= 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 >= 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.
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changes in alkaline phosphatase levels in patients with prostate cancer receiving degarelix or Leuprolide results from a 12 month comparative phase iii study
2009Co-Authors: Fritz H Schroder, Neal D Shore, Bertrand Tombal, Kurt Miller, Laurent Boccongibod, David E Crawford, Judd W Moul, Tine Kold Olesen, Boeric PerssonAbstract: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 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.