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Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Degarelix proved very effective in early clinical trials with advanced prostate cancer patients. For example, in one randomized 12-month Phase II clinical trial (the “CS21”) comparing two dose levels of degarelix against the GnRH agonist leuprolide, it was reported in 2008 that both degarelix doses were at least as effective as a standard dose of leuprolide in suppressing testosterone to castration levels (≤0.5 ng/mL). With degarelix this occurred from the third day of the trial, whereas leuprolide-treated patients had to wait much longer for this to occur. Furthermore, there were no testosterone surges with degarelix compared with 81% of leuprolide-treated patients who experienced initial surges leading to tumor flares. Degarelix also provided a faster reduction in PSA levels compared with leuprolide-treated patients, thus providing faster control of the cancer.
The prostate and seminal vesicles
Published in Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie, Bailey & Love's Short Practice of Surgery, 2018
Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie
Recently agents such as enzalutamide (a second generation androgen receptor blocker), degarelix (an LHRH antagonist), abiraterone (a drug that blocks the production of testosterone from its precursors) and taxane chemotherapy have all been shown to promote survival in metastatic prostate cancer. Many clinical trials are underway to ascertain which drugs should be used in which patients and the therapeutic landscape is changing rapidly.
Current and emerging gonadotropin-releasing hormone (GnRH) antagonists for the treatment of prostate cancer
Published in Expert Opinion on Pharmacotherapy, 2021
Mohamad Moussa, Athanasios Papatsoris, Athanasios Dellis, Mohamed Abou Chakra, Charalampos Fragkoulis
Degarelix efficacy and safety was evaluated in a pivotal study by Klotz et al involving 610 prostate cancer patients. In this open-label randomized phase III trial (CS21), patients were stratified into three groups with different ADT approach. Patients received either degarelix at a starting dose of 240 mg followed by monthly doses of 80 mg for a total of 12 months or monthly doses of 160 mg for the same period of time. The LHRH agonist arm included patients receiving Leuprolide 7.5 mg monthly. In the leuprolide arm, the administration of bicalutamide 50 mg daily was possible in order to prevent flare phemomenon. Degarelix proved not to be inferior to leuprolide in terms of achieving and maintaining testosterone castration levels for a period of 12 months with the advantage of rapid testosterone suppression with 95% of patients achieving castration levels 3 days after treatment initiation without a flare phenomenon. Moreover, patients in the degarelix arms with PSA > 20 ng/ml at therapy initiation presented a lower risk of PSA progression [24].
Relugolix: A new kid on the block among gonadotrophin-releasing hormone antagonists
Published in Arab Journal of Urology, 2021
Charalampos Fragkoulis, Ioannis Glykas, Athanasios Dellis, Iraklis Mitsogiannis, Athanasios Papatsoris
Safety of GnRH antagonists is well documented by large phase III trials in which degarelix presented a similar safety profile as GnRH agonists [13,16]. Degarelix presents injection site reactions such as pain, erythema, pruritus and swelling more frequently than GnRH agonists. In terms of hot flashes, erectile dysfunction, decreased libido and renal-related adverse events, no difference was recorded comparing degarelix with GnRH agonists [13]. Recently, Abufaraj et al. [16] published the results of a meta-analysis regarding the clinical safety and oncological outcomes of GnRH agonists vs antagonists. The authors concluded that GnRH antagonists were associated with more injection site reactions in a statistically significant way. There is a trend of less serious adverse events among patients under GnRH antagonist treatment (9.8% vs 11%). Both groups presented similar dropout rates due to adverse events. Furthermore, GnRH antagonist proved to be safer in terms of musculoskeletal and cardiovascular adverse events.
Advanced delivery of leuprorelin acetate for the treatment of prostatic cancer
Published in Expert Review of Anticancer Therapy, 2022
Axel S Merseburger, Marie Christine Roesch
The clinical benefits of treating PCa with LHRH agonists were reported in 1982, and long-acting formulations of LHRH agonists are currently the main form of ADT used in clinical practice [16]. After the injection, long-acting LHRH agonists reduce testosterone levels providing constant overstimulation of the pituitary gland, leading to inhibition of LH release and consequently to inhibition of testosterone production (Figure 1) [16]. Their effectiveness is higher compared to antiandrogen monotherapy [17–20]. With regard to LHRH antagonists, there is a lack of significant long-term data or survival evidence directly comparing the two treatment regimens. Consequently, it is impossible to define one treatment’s superiority over the other in terms of effectiveness and PCa control [2]. Nevertheless, the use of LHRH agonists in clinical practice is easier compared to degarelix – the only LHRH antagonist approved in Europe for the treatment of advanced PCa. Indeed, degarelix requires the subcutaneous administration of large volumes that frequently causes adverse reactions at the injection site, limiting its use. For instance, a post-hoc meta-analysis suggested a reduction in ADT-related cardiovascular events in the subgroup of patients with preexisting cardiovascular morbidity treated with degarelix, compared to the use of LHRH agonist [21]. Nevertheless, more recent studies suggested no evident difference regarding cardiovascular morbidity when comparing LHRH agonists versus antagonists [22,23]. This finding is also supported by the first international, randomized clinical trial that prospectively compared the cardiovascular safety of LHRH agonists and antagonists in PCa patients. There was no difference in major adverse cardiovascular events at 1 year between the two patient groups [24].