Androgen deprivation therapy(ADT)with gonadotropin-releasing hormone(GnRH)agonists and antagonists is the mainstay of advanced prostate cancer treatment.Both drug classes decrease levels of luteinizing hormone and fol...Androgen deprivation therapy(ADT)with gonadotropin-releasing hormone(GnRH)agonists and antagonists is the mainstay of advanced prostate cancer treatment.Both drug classes decrease levels of luteinizing hormone and follicle-stimulating hormones(FSH),thereby lowering testosterone to castrate levels.This is associated with adverse events(AEs),including cardiovascular(CV)disorders,bone fractures,metabolic dysfunction,and impaired cognitive function.This literature review discusses these AEs,with a focus on CV and bone-related events.A hypothesis-generating meta-analysis of six clinical trials showed a potentially increased risk for CV disorders with GnRH agonists versus the GnRH antagonist degarelix.While no study has directly compared GnRH agonists versus antagonists with a primary CV outcome,one hypothesis for this observation is that GnRH agonists lead to initial surges in FSH that may negatively impact CV health,whereas antagonists do not.GnRH agonists are associated with metabolic and cognitive AEs and while data are lacking for GnRH antagonists,no differences in risk are predicted.Other common AEs with ADT include injection site reactions,which are much more common with degarelix than with GnRH agonists,which may reflect differing administration and injection techniques.Future studies are needed to further evaluate and compare the safety profiles of GnRH agonists and antagonists,especially in patients with pre-existing CV disease and other co-morbidities.Physicians should carefully evaluate benefits and risks when prescribing ADT and ensure that side effects are well managed.展开更多
Intermittent androgen deprivation therapy(IADT)is now being increasingly opted by the treating physicians and patients with prostate cancer.The most common reason driving this is the availability of an off-treatment p...Intermittent androgen deprivation therapy(IADT)is now being increasingly opted by the treating physicians and patients with prostate cancer.The most common reason driving this is the availability of an off-treatment period to the patients that provides some relief from treatment-related side-effects,and reduced treatment costs.IADT may also delay the progression to castration-resistant prostate cancer.However,the use of IADT in the setting of prostate cancer has not been strongly substantiated by data from clinical trials.Multiple factors seem to contribute towards this inadequacy of supportive data for the use of IADT in patients with prostate cancer,e.g.,population characteristics(both demographic and clinical),study design,treatment regimen,on-and off-treatment criteria,duration of active treatment,endpoints,and analysis.The present review article focuses on seven clinical trials that evaluated the efficacy of IADT vs.continuous androgen deprivation therapy for the treatment of prostate cancer.The results from these clinical trials have been discussed in light of the factors that may impact the treatment outcomes,especially the disease(tumor)burden.Based on evidence,potential candidate population for IADT has been suggested along with recommendations for the use of IADT in patients with prostate cancer.展开更多
文摘Androgen deprivation therapy(ADT)with gonadotropin-releasing hormone(GnRH)agonists and antagonists is the mainstay of advanced prostate cancer treatment.Both drug classes decrease levels of luteinizing hormone and follicle-stimulating hormones(FSH),thereby lowering testosterone to castrate levels.This is associated with adverse events(AEs),including cardiovascular(CV)disorders,bone fractures,metabolic dysfunction,and impaired cognitive function.This literature review discusses these AEs,with a focus on CV and bone-related events.A hypothesis-generating meta-analysis of six clinical trials showed a potentially increased risk for CV disorders with GnRH agonists versus the GnRH antagonist degarelix.While no study has directly compared GnRH agonists versus antagonists with a primary CV outcome,one hypothesis for this observation is that GnRH agonists lead to initial surges in FSH that may negatively impact CV health,whereas antagonists do not.GnRH agonists are associated with metabolic and cognitive AEs and while data are lacking for GnRH antagonists,no differences in risk are predicted.Other common AEs with ADT include injection site reactions,which are much more common with degarelix than with GnRH agonists,which may reflect differing administration and injection techniques.Future studies are needed to further evaluate and compare the safety profiles of GnRH agonists and antagonists,especially in patients with pre-existing CV disease and other co-morbidities.Physicians should carefully evaluate benefits and risks when prescribing ADT and ensure that side effects are well managed.
基金Ferring Pharmaceuticals provided funding for editorial assistance.The author acknowledges Dr.Payal Bhardwaj of Tata Consultancy Services,who provided editorial assistance.
文摘Intermittent androgen deprivation therapy(IADT)is now being increasingly opted by the treating physicians and patients with prostate cancer.The most common reason driving this is the availability of an off-treatment period to the patients that provides some relief from treatment-related side-effects,and reduced treatment costs.IADT may also delay the progression to castration-resistant prostate cancer.However,the use of IADT in the setting of prostate cancer has not been strongly substantiated by data from clinical trials.Multiple factors seem to contribute towards this inadequacy of supportive data for the use of IADT in patients with prostate cancer,e.g.,population characteristics(both demographic and clinical),study design,treatment regimen,on-and off-treatment criteria,duration of active treatment,endpoints,and analysis.The present review article focuses on seven clinical trials that evaluated the efficacy of IADT vs.continuous androgen deprivation therapy for the treatment of prostate cancer.The results from these clinical trials have been discussed in light of the factors that may impact the treatment outcomes,especially the disease(tumor)burden.Based on evidence,potential candidate population for IADT has been suggested along with recommendations for the use of IADT in patients with prostate cancer.
