Recently,follicle stimulating hormone receptor was found to be selectively expressed by endothelial cells on tumor-associated blood vessels in a wide range of human cancers.In this context,we hypothesized that degarel...Recently,follicle stimulating hormone receptor was found to be selectively expressed by endothelial cells on tumor-associated blood vessels in a wide range of human cancers.In this context,we hypothesized that degarelix,a new gonadotropin-releasing hormone receptor antagonist developed for patients with prostate cancer,may have antiangiogenic effects via its capacity to block follicle stimulating hormone(FSH)production. We report the case of a patient with metastatic colon cancer exhibiting tumor progression after failure of all conventional chemotherapeutic regimens.The addition of degarelix to the last chemotherapeutic regimen was proposed as compassionate treatment.Degarelix induced a rapid decrease in FSH level.This treatment induced radiological stabilization and carcinoembryonic antigen stabilization during 1 year.Contrast-enhanced ultrasonography demonstrated reduction of tumor vas-clature.This case represents the first report of an antitumoral effect of degarelix in metastatic colon cancer and suggests an antiangiogenic property of this drug.展开更多
Objective:To establish non-inferiority of gonadotropin-releasing hormone degarelix compared with goserelin in suppressing and maintaining castrate testosterone levels from Day 28 to Day 364 in Chinese patients with pr...Objective:To establish non-inferiority of gonadotropin-releasing hormone degarelix compared with goserelin in suppressing and maintaining castrate testosterone levels from Day 28 to Day 364 in Chinese patients with prostate cancer.Methods:This is an open-label,multi-centre study in which men aged18 years were randomised in a 1:1 ratio to once-a-month subcutaneous injection of either degarelix(240/80 mg)or goserelin(3.6 mg)for 12 months.The primary endpoint was difference in 1-year cumulative probability of suppressing testosterone to ≤0.5 ng/mL.Non-inferiority was to be established if the lower 95% confidence interval(CI)limit for difference in cumulative probability between the treatment arms was greater than -10%.Secondary endpoints included cumulative probability of prostate-specific-antigen-progression-free-survival(PSA-PFS).Safety was also assessed.Results:Baseline demographics and disease characteristics were similar between degarelix(n=142)and goserelin(n=141)treatment arms.The difference in cumulative probability of maintaining castrate levels from Day 28-364 was 3.6%(95%CI:-1.5%,8.7%),demonstrating non-inferiority of degarelix.The cumulative probability of PSA-PFS at Day 364 was higher for degarelix(82.3%,95%CI:74.7%,87.7%)versus goserelin(71.7%,95%CI:63.2%,78.5%,p=0.038).Adverse events(AEs)were similar between treatment arms,except for more injection site reactions with degarelix versus goserelin.Four(2.8%)and nine(6.4%)patients discontinued due to AEs in degarelix and goserelin groups,respectively.展开更多
AIM:To conduct a systematic review and meta-analysis into the efficacy,safety,and dosage regimens of degarelix for treating prostate cancer(PCa). METHODS:Pub Med,EMBASE,the Cochrane Library,and Web of Science was syst...AIM:To conduct a systematic review and meta-analysis into the efficacy,safety,and dosage regimens of degarelix for treating prostate cancer(PCa). METHODS:Pub Med,EMBASE,the Cochrane Library,and Web of Science was systematically searched to identify randomized controlled trials(RCTs) comparing degarelix(240/80 mg vs 240/160 mg) to the gonadotropin-releasing hormone agonists,goserelin and leuprolide,for the treatment of PCa. Two independent reviewers screened putative studies,assessed the risk of bias,and then extracted pertinent data. Analyses were performed using Review Manager 5.2. RESULTS:Seven papers from six RCTs,involving 1204 patients,were identified. The present meta-analysis showed that treatment with 240/160 mg degarelix is more effective and has fewer adverse events(AEs) relative to conventional 240/80 mg regimen. Degarelix significantly decreased International Prostate Symptom Scores [standardized mean differences(SMD) =-0.32,95%CI:-0.51 to-0.12,P = 0.02] and caused fewer AEs(SMD =-0.28,95%CI:-0.48 to-0.07,P = 0.008) than goserelin. Degarelix suppressed testosterone and prostate-specific antigen significantly faster than leuprolide. CONCLUSION:Degarelix is a useful option in the treatment of advanced PCa. Degarelix 240/160 mgregimen was superior to a 240/80 mg regimen. More rigorously designed RCTs are urgently needed to confirm the efficacy of degarelix.展开更多
Objective: To obtain complete prostatic cell death in the treatment of early stage prostate cancer by High Intensity Focused Ultrasound (HIFU) therapy, we use Degarelix (GnRH antagonist) twice simultaneously. Patients...Objective: To obtain complete prostatic cell death in the treatment of early stage prostate cancer by High Intensity Focused Ultrasound (HIFU) therapy, we use Degarelix (GnRH antagonist) twice simultaneously. Patients and Methods: The first Degarelix subcutaneous injection was made two weeks before HIFU therapy, and second Degarelix was applied two weeks after the HIFU therapy. No additional maintenance Degarelix was used. To confirm the apoptosis induced by Degarelix, specimens obtained by transurethral resection simultaneously on HIFU were stained with caspase 3 and TUNEL. PSA was monitored every three months after this combination therapy as long as two years. These PSA values were compared with those who previously treated with HIFU without Degarelix. Results: Nine T1cN0M0 prostate cancer patients were enrolled to “HIFU + Degarelix” therapy. Pre treatment mean PSA level was 6.11 ± 1.83 ng/ml (SD), and PSA 3 months after the treatment was 0.02 ± 0.02. These low PSA levels continued thereafter (0.16 ng/ml ± 0.19 at 24 months). The mean pretreatment PSA level of the 34 patients underwent HIFU without Degarelix was 11.07 ± 13.9 ng/ml, 3 months post HIFU was 1.68 ± 3.04, (2.80 ± 3.97 at 24 months). Caspase 3 and TUNEL were positive on the glandular cells in TUR specimens of “HIFU + Degarelix” patients, suggesting Degarelix induced apoptosis. Conclusion: Although the number of our patients was small, the results of “Short course Degarelix + HIFU” would be promising for better long-term outcome than HIFU mono-therapy.展开更多
<strong>Objective:</strong> Upfront docetaxel use for hormone na<span style="white-space:nowrap;">ï</span>ve advanced prostate cancer is reported that it successfully delayed...<strong>Objective:</strong> Upfront docetaxel use for hormone na<span style="white-space:nowrap;">ï</span>ve advanced prostate cancer is reported that it successfully delayed the progression to hormone refractory stage, though the adequate methodology to obtain the maximum effect is unclear. We investigated these issues from our experiences of upfront docetaxel use with LH-RH antagonist for metastatic hormone sensitive prostate cancer, aiming at the prevention of epithelial-mesenchymal transition (EMT) for apoptosis tolerance. <strong>Patients and Methods:</strong> Of 31 stage IV new prostate cancer patients treated with upfront docetaxel and LH-RH antagonist (Degarelix), 25 patients who could be followed more than 12 months (mean 36.2 months) were analyzed. Docetaxel was used two to three courses basically 75 mg/m2 dose initializing two weeks after the induction of first Degarelix. <strong>Results:</strong> The clinical course was divided clearly to two groups according to prostate specific antigen (PSA) values. Of 25 patients, 12 patient’s PSA did not decrease below 0.1 ng/ml within 6 months (group A) and gradually rose afterwards. PSA in another 13 patients (group B) decreased below 0.1 within 6 months and kept below 0.1 during the follow up period. Although statistically not significant, the initial group A’s PSA was higher than group B’s (average 1308 and 353 ng/ml), however, number of metastasis, Gleason sum, and bone metastatic extent of disease showed no difference between them. Among group B patients, 7 cases had only upfront docetaxel and hormonal therapy, and some of these patients showed only atrophic gland and fibrotic tissue at second prostate biopsy (specimens after more than two years of therapy), suggesting complete response. <strong>Conclusion:</strong> Our study suggested that PSA value at 6 months may predict the outcome of whole therapy. Patients showing PSA less than 0.1 ng/ml at 6 months and requiring no therapy other than docetaxel and hormone may be induced to complete response. Upfront docetaxel with LH-RH antagonist may prevent EMT for obtaining apoptosis tolerance, in case the patient does not have the castration-resistant clone at the beginning of the therapy (group B).展开更多
文摘Recently,follicle stimulating hormone receptor was found to be selectively expressed by endothelial cells on tumor-associated blood vessels in a wide range of human cancers.In this context,we hypothesized that degarelix,a new gonadotropin-releasing hormone receptor antagonist developed for patients with prostate cancer,may have antiangiogenic effects via its capacity to block follicle stimulating hormone(FSH)production. We report the case of a patient with metastatic colon cancer exhibiting tumor progression after failure of all conventional chemotherapeutic regimens.The addition of degarelix to the last chemotherapeutic regimen was proposed as compassionate treatment.Degarelix induced a rapid decrease in FSH level.This treatment induced radiological stabilization and carcinoembryonic antigen stabilization during 1 year.Contrast-enhanced ultrasonography demonstrated reduction of tumor vas-clature.This case represents the first report of an antitumoral effect of degarelix in metastatic colon cancer and suggests an antiangiogenic property of this drug.
文摘Objective:To establish non-inferiority of gonadotropin-releasing hormone degarelix compared with goserelin in suppressing and maintaining castrate testosterone levels from Day 28 to Day 364 in Chinese patients with prostate cancer.Methods:This is an open-label,multi-centre study in which men aged18 years were randomised in a 1:1 ratio to once-a-month subcutaneous injection of either degarelix(240/80 mg)or goserelin(3.6 mg)for 12 months.The primary endpoint was difference in 1-year cumulative probability of suppressing testosterone to ≤0.5 ng/mL.Non-inferiority was to be established if the lower 95% confidence interval(CI)limit for difference in cumulative probability between the treatment arms was greater than -10%.Secondary endpoints included cumulative probability of prostate-specific-antigen-progression-free-survival(PSA-PFS).Safety was also assessed.Results:Baseline demographics and disease characteristics were similar between degarelix(n=142)and goserelin(n=141)treatment arms.The difference in cumulative probability of maintaining castrate levels from Day 28-364 was 3.6%(95%CI:-1.5%,8.7%),demonstrating non-inferiority of degarelix.The cumulative probability of PSA-PFS at Day 364 was higher for degarelix(82.3%,95%CI:74.7%,87.7%)versus goserelin(71.7%,95%CI:63.2%,78.5%,p=0.038).Adverse events(AEs)were similar between treatment arms,except for more injection site reactions with degarelix versus goserelin.Four(2.8%)and nine(6.4%)patients discontinued due to AEs in degarelix and goserelin groups,respectively.
文摘AIM:To conduct a systematic review and meta-analysis into the efficacy,safety,and dosage regimens of degarelix for treating prostate cancer(PCa). METHODS:Pub Med,EMBASE,the Cochrane Library,and Web of Science was systematically searched to identify randomized controlled trials(RCTs) comparing degarelix(240/80 mg vs 240/160 mg) to the gonadotropin-releasing hormone agonists,goserelin and leuprolide,for the treatment of PCa. Two independent reviewers screened putative studies,assessed the risk of bias,and then extracted pertinent data. Analyses were performed using Review Manager 5.2. RESULTS:Seven papers from six RCTs,involving 1204 patients,were identified. The present meta-analysis showed that treatment with 240/160 mg degarelix is more effective and has fewer adverse events(AEs) relative to conventional 240/80 mg regimen. Degarelix significantly decreased International Prostate Symptom Scores [standardized mean differences(SMD) =-0.32,95%CI:-0.51 to-0.12,P = 0.02] and caused fewer AEs(SMD =-0.28,95%CI:-0.48 to-0.07,P = 0.008) than goserelin. Degarelix suppressed testosterone and prostate-specific antigen significantly faster than leuprolide. CONCLUSION:Degarelix is a useful option in the treatment of advanced PCa. Degarelix 240/160 mgregimen was superior to a 240/80 mg regimen. More rigorously designed RCTs are urgently needed to confirm the efficacy of degarelix.
文摘Objective: To obtain complete prostatic cell death in the treatment of early stage prostate cancer by High Intensity Focused Ultrasound (HIFU) therapy, we use Degarelix (GnRH antagonist) twice simultaneously. Patients and Methods: The first Degarelix subcutaneous injection was made two weeks before HIFU therapy, and second Degarelix was applied two weeks after the HIFU therapy. No additional maintenance Degarelix was used. To confirm the apoptosis induced by Degarelix, specimens obtained by transurethral resection simultaneously on HIFU were stained with caspase 3 and TUNEL. PSA was monitored every three months after this combination therapy as long as two years. These PSA values were compared with those who previously treated with HIFU without Degarelix. Results: Nine T1cN0M0 prostate cancer patients were enrolled to “HIFU + Degarelix” therapy. Pre treatment mean PSA level was 6.11 ± 1.83 ng/ml (SD), and PSA 3 months after the treatment was 0.02 ± 0.02. These low PSA levels continued thereafter (0.16 ng/ml ± 0.19 at 24 months). The mean pretreatment PSA level of the 34 patients underwent HIFU without Degarelix was 11.07 ± 13.9 ng/ml, 3 months post HIFU was 1.68 ± 3.04, (2.80 ± 3.97 at 24 months). Caspase 3 and TUNEL were positive on the glandular cells in TUR specimens of “HIFU + Degarelix” patients, suggesting Degarelix induced apoptosis. Conclusion: Although the number of our patients was small, the results of “Short course Degarelix + HIFU” would be promising for better long-term outcome than HIFU mono-therapy.
文摘<strong>Objective:</strong> Upfront docetaxel use for hormone na<span style="white-space:nowrap;">ï</span>ve advanced prostate cancer is reported that it successfully delayed the progression to hormone refractory stage, though the adequate methodology to obtain the maximum effect is unclear. We investigated these issues from our experiences of upfront docetaxel use with LH-RH antagonist for metastatic hormone sensitive prostate cancer, aiming at the prevention of epithelial-mesenchymal transition (EMT) for apoptosis tolerance. <strong>Patients and Methods:</strong> Of 31 stage IV new prostate cancer patients treated with upfront docetaxel and LH-RH antagonist (Degarelix), 25 patients who could be followed more than 12 months (mean 36.2 months) were analyzed. Docetaxel was used two to three courses basically 75 mg/m2 dose initializing two weeks after the induction of first Degarelix. <strong>Results:</strong> The clinical course was divided clearly to two groups according to prostate specific antigen (PSA) values. Of 25 patients, 12 patient’s PSA did not decrease below 0.1 ng/ml within 6 months (group A) and gradually rose afterwards. PSA in another 13 patients (group B) decreased below 0.1 within 6 months and kept below 0.1 during the follow up period. Although statistically not significant, the initial group A’s PSA was higher than group B’s (average 1308 and 353 ng/ml), however, number of metastasis, Gleason sum, and bone metastatic extent of disease showed no difference between them. Among group B patients, 7 cases had only upfront docetaxel and hormonal therapy, and some of these patients showed only atrophic gland and fibrotic tissue at second prostate biopsy (specimens after more than two years of therapy), suggesting complete response. <strong>Conclusion:</strong> Our study suggested that PSA value at 6 months may predict the outcome of whole therapy. Patients showing PSA less than 0.1 ng/ml at 6 months and requiring no therapy other than docetaxel and hormone may be induced to complete response. Upfront docetaxel with LH-RH antagonist may prevent EMT for obtaining apoptosis tolerance, in case the patient does not have the castration-resistant clone at the beginning of the therapy (group B).
