抑那通治疗前列腺癌的新进展.pptx

抑那通治疗前列腺癌的新进展,AUA(2010),内分泌治疗新进展,Radiotherapy combined with androgen deprivation vs.androgen deprivation alone in clinically locally advanced prostate caner in a multicenter randomised phase III study,Nicolas Mottet,France.,AUA(2010),内分泌治疗新进展,INTRODUCTION AND OBJECTIVES,In locally advanced disease,the combination of radiotherapy(RT)and androgen deprivation(ADT)is,superior to,RT alone.,But ADT with an analogue,has never been,compared to combined modality.,We report a phase III randomised trial in locally advanced PCa,comparing a combined modality and ADT only.,AUA(2010),内分泌治疗新进展,METHODS,In this French,multicenter,open,randomised trial,patients less than 80 years,with histologically confirmed PCa,T3-4,or pT3(biopsy)N0M0,were included.,They were centrally randomised in 2 parallel groups to either,ADT alone,(leuprorelin 11.25 mg SR,1 sc injection every 3 months for 3 years or,the same ADT combined with RT,starting within 3 months over 7 weeks.,AUA(2010),内分泌治疗新进展,RESULTS,HT,HT+RT,P,N,131,133,Mean Age,70.5,70.7,0.63,Mean PSA baseline,51.77,41.50,0.79,Median PFS(days),1264,2544,0.0005,PFS(5 year)(%),15.4,64.7,0.0005,Biological progression(%),71.5,19.5,0.0001,Clinical progression(%),37.7,11.3,110 mg/dL,serum triglyceride level 150 mg/dL,serum high-density lipoprotein level102 cm,Blood pressure of 130/85 mmHg.,AUA(2010),内分泌治疗新进展,RESULTS,MS was diagnosed in 27 of the 53 patients subjected to ADT(51.9%)while it was detected in 35 of the 105 age-matched controls(33.3%),p=0.020,.,However the prevalence of MS was 35.8%(19/53)in men without PC and 30.8%(16/52)in men with PC,p=0.365,.,AUA(2010),内分泌治疗新进展,CONCLUSION,Although the limited number cases and controls included in this interim analysis,a,significant increase,in the prevalence of MS was observed in PC patients subjected to ADT.,AUA(2010),内分泌治疗新进展,Metabolic change after androgen deprivation therapy in Korean men with prostate cancer,Chang Hoo Park,Korea,AUA(2010),内分泌治疗新进展,INTRODUCTION AND OBJECTIVES,In men with prostate cancer,Androgen deprivation therapy shows a variety well recognized metabolic alteration.,To better characterize the metabolic effects of androgen deprivation therapy in Korean men,we evaluated the changes in,fat thickness,bone mineral density,(BMD),body mass index,(BMI),and,levels of hemoglobin,(Hb)and,cholesterol,.,We also compared them with data from healthy subjects.,AUA(2010),内分泌治疗新进展,METHODS,From December 2002 to December 2008,148 Korean men treated with leuprolide depot and bicalutamide for prostate cancer and 100 healthy subjects were investigated included change from baseline to month 12 in,fat thickness,bone mineral density,(BMD),body mass index,(BMI),and,levels of hemoglobin,(Hb)and,cholesterol,.,AUA(2010),内分泌治疗新进展,RESULTS,ADT,Control,P,N,148,100,Fat thickness(mm),20.4,16.9,0.05,BMD=bone mineral density,0.91,0.94,0.05,BMI(kg/m,2,),23.9,22.9,0.05,There are no significant changes in hemoglobin and cholesterol levels.,AUA(2010),内分泌治疗新进展,CONCLUSION,Our results show that Korean men with prostate cancer have increased abdominal subcutaneous fat and BMI and have decreased BMD during androgen deprivation therapy.,These increases the risk of bone fracture and complication related obesity.Therefore,BMD will be checked periodically and carry out exercise program to prevention obesity during androgen deprivation therapy.,AUA(2010),内分泌治疗新进展,Sarcopenia in men receiving androgen deprivation therapy for prostate cancer:a prospective 3-year study.,Matthew R.Smith,CA.,AUA(2010),内分泌治疗新进展,INTRODUCTION AND OBJECTIVES,Androgen deprivation therapy(ADT)for prostate cancer decreases bone mineral density and increases fracture risk.,Studies with limited sample size and observational periods have reported that ADT is also associated with sarcopenia or loss of muscle(lean body mass,LBM).,We now report the prospective changes in LBM in a subset of men from that study.,AUA(2010),内分泌治疗新进展,METHODS,Men undergoing ADT for nonmetastatic prostate cancer at 38 centers in North America were randomized to denosumab or placebo.,A total of 248 subjects(130 denosumab,118 placebo)with a baseline and with at least 1 on-study LBM result were considered evaluable and included in this analysis.,AUA(2010),内分泌治疗新进展,METHODS,Subjects were stratified at baseline by age(6 months).,LBM was measured by total body dual-energy x-ray absorptiometry at baseline and at 12,24,and 36 months.,AUA(2010),内分泌治疗新进展,RESULTS,From baseline to month 12,mean LBM,decreased,significantly by 1.0%(p=.0004).,Significant,decreases,in LBM were also observed at month 24(2.1%,p.0001)and month 36(2.4%,p.0001).,AUA(2010),内分泌治疗新进展,RESULTS,Men aged 70 years(n=127)had significantly greater changes in LBM at all measured time points.,At 36 months,LBM decreased by 2.8%in men aged 70 years compared with a decrease of 0.9%in younger men(p=0.035).,AUA(2010),内分泌治疗新进展,CONCLUSION,This is the largest and longest prospective study undertaken to describe the natural history of,muscle loss,in men undergoing ADT therapy for prostate cancer.,LBM significantly decreased at 12,24,and 36 months.,Decreases in LBM were greatest in older men and in those who had short duration of ADT at study entry.,AUA(2010),内分泌治疗新进展,Recovery of testosterone and PSA after cessation of long term luteinizing hormone releasing hormone agonist(LHRH)therapy for prostate cancer:a prospective trial.,Matthew McIntyre,Charleston,SC,AUA(2010),内分泌治疗新进展,INTRODUCTION AND OBJECTIVES,The use of hormonal manipulation in the treatment of prostate cancer has been an option since the time of Huggins initial description.,However,many questions remain regarding timing of initiation,and length of treatment interval for medically induced castration.,AUA(2010),内分泌治疗新进展,INTRODUCTION AND OBJECTIVES,The effects of long term LHRH agonist on the hypothymalic pituitary gonadal axis are also not completely understood.,We sought to examine the effects of long term LHRH agonist on recovery of testosterone and PSA.,AUA(2010),内分泌治疗新进展,METHODS,Hormonal ablation was discontinued and serial testosterone and PSA measurements were obtained on a three monthly basis.,Patients were counseled regarding restarting hormonal therapy if 2 consecutive rises in PSA were observed.Patients were allowed to stay off hormones and on study if they desired.,AUA(2010),内分泌治疗新进展,METHODS,We organized a prospective trial examining men at the Veterans Administration Hospital who had been on at least 48 months of an LHRH agonist.,Other inclusion criteria were that PSA be less than 3ng/ml,and not rising for the 2 consecutive values prior to discontinuing hormones.,AUA(2010),内分泌治疗新进展,RESULTS,Nineteen patients were enrolled in the study between 2007 and 2008.,The mean age was 75 years.,The mean duration of hormonal therapy was 88 months.,AUA(2010),内分泌治疗新进展,RESULTS,Ten(53%)patients were on hormones for biochemical recurrence,；,Two(10%)for metastatic disease,；,Seven(36%)as primary therapy.,AUA(2010),内分泌治疗新进展,RESULTS,Eleven(58%)patients had 2 consecutive rises in PSA;,The mean time to see two consecutive rises was 11 months.,AUA(2010),内分泌治疗新进展,RESULTS,The mean time off therapy prior to a rise in PSA 0.1ng/ml above base line for all patients and those with 2 consecutive rises was 15.4 and 9.5 months respectively.,The mean base line PSA,mean PSA at one,and at two years off therapy was 0.3ng/ml,1.1ng/ml,and 5ng/ml respectively.,Mean testosterone at base line,one,and two years off therapy was 13.9ng/ml,76ng/ml,and 150.6ng/ml respectively.,AUA(2010),内分泌治疗新进展,RESULTS,Twelve(63%)patients had recovery of testosterone above 50ng/dl.,Four(21%)patients remained castrate off therapy a mean of 20 months.,The mean time to testosterone recovery was 12.8 months.,Two(10.5%)patients in the study have died.One death was attributed to prostate cancer.,AUA(2010),内分泌治疗新进展,CONCLUSION,The recovery of testosterone and significant elevations of PSA after long term LHRH agonist therapy is significantly delayed in most patients.,This helps to support the concept of,intermittent androgen ablation,which has benefits in quality of life and reduced cost of therapy.,Data on file,手术去势的副作用,增加心血管疾病和糖尿病发病率,Data on file,手术去势的副作用,增加骨折发病率,抑那通通过抑制雄性激素的作用而抑制大白鼠前列腺肿瘤的增殖,醋酸亮丙瑞林水溶液,0.333mg/kg/,日（,1,日,1,次投药,),醋酸亮丙瑞林水溶液,0.333mg/kg/,日（,1,日,2,次投药,),抑那通,相当于,0.333mg/kg/,日（,1,月,1,次投药,),阉割,肿瘤移植后的天数,肿 瘤 体 积,(cm),对照,醋酸亮丙瑞林水溶液,1mg/kg/,日（,1,日,1,次投药,),抑那通与睾丸切除术抗肿瘤作用比较,抑那通治疗前列腺癌的综合效果,抑那通治疗前列腺癌各病灶的疗效,抑那通改善前列腺癌各种症状的效果明显,抑那通治疗前列腺癌从起效到部分缓解的时间,间歇疗法与持续疗法患者生存率相当,Data on file,抑那通间歇疗法显著降低前列腺体积,第,1,周期,第,2,周期,前列腺体积变化比例,(%),Bruchovsky N,et al.Cancer.2006 Jul 15;107(2):389-95,抑那通间歇疗法迅速降低,PSA,值,到达,PSA,最低值所需时间,(,月,),Higano CS,et al.Urology.1996 Nov;48(5):800-4,间歇疗法减少骨质丢失，降低副反应发生率,Uif Tunn 2007 Bju International 99,supplement 1,19-22,Data on file,间歇期雄激素明显恢复，可改善患者生活质量,间歇疗法有利于患者性功能恢复,N.A.Spry,et al European Journal of Cancer 42(2006):1083-1092,间歇期暂停用药，大幅度降低治疗成本,总 结,有效治疗前列腺癌,患者生存率与持续疗法相当,与去势疗法相比，副作用显著降低,改善性功能，提高生活质量,降低治疗成本,抑那通间歇疗法优势突出,抑那通,3.75mg,预充式注射器,现有剂型,上市新剂型,