抑那通治疗前列腺癌的新进展课件.ppt

1、抑那通治疗前列腺癌的新进展AUA(2019)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(2019)内分泌治疗新进展INTRODUCTION AND OBJECTIVES In locally advanced disease,the co

2、mbination 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(2019)内分泌治疗新进展METHODS In this French mu

3、lticenter,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

4、RT starting within 3 months over 7 weeks.AUA(2019)内分泌治疗新进展RESULTSHTHT+RTPN131133Mean Age70.570.70.63Mean PSA baseline51.7741.500.79Median PFS(days)126425440.0005PFS(5 year)(%)15.464.70.0005Biological progression(%)71.519.50.0001Clinical progression(%)37.711.3110 mg/dL serum triglyceride level 150 mg

5、/dL serum high-density lipoprotein level102 cm Blood pressure of 130/85 mmHg.AUA(2019)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 withou

6、t PC and 30.8%(16/52)in men with PC,p=0.365.AUA(2019)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(2019)内分泌治疗新进展 Metabolic change after androgen depri

7、vation therapy in Korean men with prostate cancer Chang Hoo Park,KoreaAUA(2019)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 therap

8、y 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(2019)内分泌治疗新进展METHODS From December 2019 to December 2019,148 Korean men treated with leuproli

9、de 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(2019)内分泌治疗新进展RESULTSADTControlPN148100Fat thickness(mm)20

10、.416.90.05BMD=bone mineral density0.910.940.05BMI(kg/m2)23.922.90.05There are no significant changes in hemoglobin and cholesterol levels.AUA(2019)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

11、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(2019)内分泌治疗新进展 Sarcopenia in men receiving androgen deprivati

12、on therapy for prostate cancer:a prospective 3-year study.Matthew R.Smith,CA.AUA(2019)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 re

13、ported 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(2019)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 den

14、osumab 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(2019)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-energ

15、y x-ray absorptiometry at baseline and at 12,24,and 36 months.AUA(2019)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(2019)内分泌治疗新进展RESULTS Men aged 70 ye

16、ars(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(2019)内分泌治疗新进展CONCLUSION This is the largest and longest prospective study undertaken to describe the natur

17、al 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(2019)内分泌治疗新进展 Recovery of testosterone and PSA after cessation of l

18、ong term luteinizing hormone releasing hormone agonist(LHRH)therapy for prostate cancer:a prospective trial.Matthew McIntyre,Charleston,SCAUA(2019)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 ini

19、tial description.However,many questions remain regarding timing of initiation,and length of treatment interval for medically induced castration.AUA(2019)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 unders

20、tood.We sought to examine the effects of long term LHRH agonist on recovery of testosterone and PSA.AUA(2019)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 th

21、erapy if 2 consecutive rises in PSA were observed.Patients were allowed to stay off hormones and on study if they desired.AUA(2019)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 inclus

22、ion criteria were that PSA be less than 3ng/ml,and not rising for the 2 consecutive values prior to discontinuing hormones.AUA(2019)内分泌治疗新进展RESULTS Nineteen patients were enrolled in the study between 2019 and 2019.The mean age was 75 years.The mean duration of hormonal therapy was 88 months.AUA(201

23、9)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(2019)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(2019)内分泌治疗新进展RESULTS The

24、 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

25、line,one,and two years off therapy was 13.9ng/ml,76ng/ml,and 150.6ng/ml respectively.AUA(2019)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(

26、10.5%)patients in the study have died.One death was attributed to prostate cancer.AUA(2019)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 intermitten

27、t androgen ablation which has benefits in quality of life and reduced cost of therapy.Data on fileData on file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移植后的天数肿肿 瘤瘤 体体 积积(cm)对照醋酸亮丙瑞林水溶液1mg/kg/日（1日1次投药)综 合 效 果（完 全 病 例）在

28、 1 2 周 时 亮 丙 瑞 林 的 有 效 率（C R+P R）如 下，在 批 准 上 市 时 为 5 3.9%，在 市 场 销 售 后 的 调 查 成 绩 为 8 1.2%。病 例 数 有 效 率（%）病 例 数 有 效 率（%）上 市 销 售 后 调 查 成 绩C RC RP RP RS ta b leS ta b leN CN CP DP D1 0 26 8 15 3.98 1.2002 02 04 04 06 06 08 08 01 0 01 0 0注)用 法 用 量 通 常 成 人 每 四 周 皮 下 注 射 一 次 每 次 3.7 5 m g批 准 上 市 时病灶 有效率（%）C

29、R+PR105581450.513.864.3020406080100骨淋巴结各病灶的效果在周时的病灶效果，前列腺为，骨转移灶为，淋巴节转移为。1250.5%13.8%64.3%前列腺病例数批准上市时资料汇总转移灶在各症状的临床效果中，特别对于排尿障碍有较高的改善率。症状别的临床效果批准上市时资料汇集 上市后调查结果（1998年12月汇集）症状病例数改善率（）%病例数改善率（）%排尿障碍排尿困难急性尿闭尿频尿痛血尿残尿感贫血腰痛骨疼痛P.S.*P.S.:P erform ance st atus症状消失 症状减轻20406066.046.476.735.674.460.857.69.528.4

30、30.321.783.342.1535411035091331483631481279932755712153819266186.768.426.326.966.084.976.385.470.384.268.274.718.959.871.733.010077.293.384.742.157.784.98010020406080100症状消失（）5/5100注意：本制剂为持续4周的缓释制剂，如果以超过4周的间隔投药，则由于下垂体-性腺系剌激作用，将使血清睾丸素浓度再次上升，临床上会有暂时恶化的危险，因此请遵守4周1次的用法。批准上市时资料汇总至起效时的天数及到达PR 时的天数在12周时判定为

31、PR的病例（含CR1的病例），至起效时的天数平均为27.5日，至到达PR时的天数平均为51.0日。病例数 天数（天）080402060555527.551.0至起效时的天数至到达PR时的天数关于使用上的注意事项，请参照“概要栏”Data on file第1周期第2周期前列腺体积变化比例(%)Bruchovsky N,et al.Cancer.2019 Jul 15;107(2):389-95到达PSA最低值所需时间(月)Higano CS,et al.Urology.2019 Nov;48(5):800-4Uif Tunn 2019 Bju International 99,supplement 1,19-22Data on fileN.A.Spry,et al European Journal of Cancer 42(2019):1083-1092抑那通3.75mg预充式注射器现有剂型现有剂型上市新剂型上市新剂型