抑那通治療前列腺癌的新進(jìn)展

1、AUA(2010)內(nèi)分泌治療新進(jìn)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)內(nèi)分泌治療新進(jìn)展 INTRODUCTION AND OBJECTIVES In locally advanced disease, the combinatio

2、n 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)內(nèi)分泌治療新進(jìn)展 METHODS In this French m

3、ulticenter, 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 com

4、bined with RT starting within 3 months over 7 weeks. AUA(2010)內(nèi)分泌治療新進(jìn)展 RESULTS HTHT+RTP N131133 Mean Age70.570.70.63 Mean PSA baseline51.7741.500.79 Median PFS (days)126425440.0005 PFS (5 year) (%)15.464.70.0005 Biological progression (%)71.519.50.0001 Clinical progression (%)37.711.3110 mg/dL serum

5、 triglyceride level 150 mg/dL serum high-density lipoprotein level102 cm Blood pressure of 130/85 mmHg. AUA(2010)內(nèi)分泌治療新進(jìn)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

6、 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)內(nèi)分泌治療新進(jìn)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)內(nèi)

7、分泌治療新進(jìn)展 Metabolic change after androgen deprivation therapy in Korean men with prostate cancer Chang Hoo Park, Korea AUA(2010)內(nèi)分泌治療新進(jìn)展 INTRODUCTION AND OBJECTIVES In men with prostate cancer, Androgen deprivation therapy shows a variety well recognized metabolic alteration. To better characterize th

8、e 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)內(nèi)分泌治療新進(jìn)展 METHODS From Decemb

9、er 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 chol

10、esterol. AUA(2010)內(nèi)分泌治療新進(jìn)展 RESULTS ADTControlP N148100 Fat thickness(mm)20.416.90.05 BMD=bone mineral density0.910.940.05 BMI (kg/m2)23.922.90.05 There are no significant changes in hemoglobin and cholesterol levels. AUA(2010)內(nèi)分泌治療新進(jìn)展 CONCLUSION Our results show that Korean men with prostate cancer

11、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 d

12、eprivation therapy. AUA(2010)內(nèi)分泌治療新進(jìn)展 Sarcopenia in men receiving androgen deprivation therapy for prostate cancer: a prospective 3-year study. Matthew R. Smith,CA. AUA(2010)內(nèi)分泌治療新進(jìn)展 INTRODUCTION AND OBJECTIVES Androgen deprivation therapy (ADT) for prostate cancer decreases bone mineral density and

13、 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)內(nèi)分泌治療新進(jìn)展 METHODS Men under

14、going 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)內(nèi)分泌治療新進(jìn)展

15、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)內(nèi)分泌治療新進(jìn)展 RESULTS From baseline to month 12, mean LBM decreased significantly by 1.0% (p=.0004). Significant decreases in

16、LBM were also observed at month 24 (2.1%, p.0001) and month 36 (2.4%, p.0001). AUA(2010)內(nèi)分泌治療新進(jìn)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

17、 men (p=0.035). AUA(2010)內(nèi)分泌治療新進(jìn)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 me

18、n and in those who had short duration of ADT at study entry. AUA(2010)內(nèi)分泌治療新進(jìn)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)內(nèi)分泌治療新進(jìn)展 INTRO

19、DUCTION 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)內(nèi)分泌

20、治療新進(jìn)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)內(nèi)分泌治療新進(jìn)展 METHODS Hormonal ablation was disco

21、ntinued 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)內(nèi)分泌治療新進(jìn)展 METHODS W

22、e 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)內(nèi)分泌治療新進(jìn)展 RESU

23、LTS 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)內(nèi)分泌治療新進(jìn)展 RESULTS Ten (53%) patients were on hormones for biochemical recurrence； Two (10%) for metastatic disease； Seven (36%) as primary t

24、herapy. AUA(2010)內(nèi)分泌治療新進(jìn)展 RESULTS Eleven (58%) patients had 2 consecutive rises in PSA; The mean time to see two consecutive rises was 11 months. AUA(2010)內(nèi)分泌治療新進(jìn)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 wa

25、s 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)內(nèi)分泌治療新進(jìn)展 RESULTS Twe

26、lve (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)內(nèi)分泌治療新進(jìn)展 CO

27、NCLUSION 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

28、Data on file 抑那通通過抑制雄性激素 的作用而抑制大白鼠前列 腺腫瘤的增殖 醋酸亮丙瑞林水溶液 0.333mg/kg/日（1日1次投藥) 醋酸亮丙瑞林水溶液 0.333mg/kg/日（1日2次投藥) 抑那通 相當(dāng)于0.333mg/kg/日（1月1次投藥) 閹割 腫瘤移植后的天數(shù)腫瘤移植后的天數(shù) 腫腫 瘤瘤 體體 積積(cm) 對照 醋酸亮丙瑞林水溶液 1mg/kg/日（1日1次投藥) 綜 合 效 果 （ 完 全 病 例 ） 在 12周 時(shí) 亮 丙 瑞 林 的 有 效 率 （ CR+PR） 如 下 ， 在 批 準(zhǔn) 上 市 時(shí) 為 53.9%， 在 市 場 銷 售 后 的 調(diào) 查 成

29、績 為 81.2%。 病 例 數(shù) 有 效 率 （ %） 病 例 數(shù) 有 效 率 （ %） 上 市 銷 售 后 調(diào) 查 成 績 C R C R P R P R S table S table N C N C P D P D 10 2 68 1 53 .9 81 .2 0 0 2 0 2 0 4 0 4 0 6 0 6 0 8 0 8 0 1 0 0 1 0 0 注 ) 用 法 用 量 通 常 成 人 每 四 周 皮 下 注 射 一 次 每 次 3.75mg 批 準(zhǔn) 上 市 時(shí) 病灶 有效率（%） CR+PR 105 58 14 50.5 13.8 64.3 0 2040 60 80 100 骨

30、淋巴結(jié) 各病灶的效果 在周時(shí)的病灶效果，前列腺為，骨轉(zhuǎn)移灶為，淋巴節(jié)轉(zhuǎn)移為。1250.5%13.8%64.3% 前列腺 病例數(shù) 批準(zhǔn)上市時(shí)資料匯總 轉(zhuǎn) 移 灶 在 各癥 狀 的臨 床 效 果中 ， 特別 對 于排 尿 障礙 有 較 高的 改 善率 。 癥 狀 別 的 臨 床 效 果 批 準(zhǔn) 上 市 時(shí) 資 料 匯 集 上 市 后 調(diào) 查 結(jié) 果 （ 19 9 8年 1 2 月 匯 集 ） 癥 狀病 例 數(shù)改 善 率 （）%病 例 數(shù)改 善 率 （）% 排 尿 障 礙 排 尿困 難 急 性尿 閉 尿 頻 尿 痛 血 尿 殘 尿感 貧 血 腰 痛 骨 疼痛 P .S .* *P .S .:P er

31、form ance status 癥 狀消 失 癥 狀減 輕 204060 66.046.4 76.7 35.6 74.4 60.8 57.6 9.5 28.4 30.3 21.7 83.3 42.1 53 541 103 509 133 148 363 148 127 99 327 5 57 12 15 38 19 26 61 86.7 68.4 26.3 26.9 66.0 84.976.3 85.4 70.3 84.2 68.2 74.7 18.9 59.8 71.7 33.0 100 77.2 93.3 84.7 42.1 57.7 84.9 80 100204060 80 100 癥

32、 狀 消 失（）5/5100 注意：本制劑為持續(xù)4周的緩釋制劑，如果以超過4周的間隔投藥，則由于下垂體-性腺系剌激作用，將使血清睪丸素 濃度再次上升，臨床上會(huì)有暫時(shí)惡化的危險(xiǎn)，因此請遵守4周1次的用法。 批準(zhǔn)上市時(shí)資料匯總 至起效時(shí)的天數(shù)及到達(dá)P R 時(shí)的天數(shù) 在12周時(shí)判定為PR的病例（含CR1的病例），至起效時(shí)的天數(shù)平均為27.5日，至到達(dá)PR 時(shí)的天數(shù)平均為51.0日。 病例數(shù) 天數(shù)（天） 0 80402060 55 55 27.5 51.0 至起效時(shí)的 天數(shù) 至到達(dá)PR時(shí)的 天數(shù) 關(guān)于使用上的注意事項(xiàng)，請參照“概要欄” Data on file 第1周期第2周期 前列腺體積變化比例(%

33、) Bruchovsky N, et al. Cancer.2006 Jul 15;107(2):389-95 到達(dá)PSA最低值所需時(shí)間(月) Higano CS, et al. Urology.1996 Nov;48(5):800-4 Uif Tunn 2007 Bju International 99,supplement 1,19-22 Data on file N.A.Spry,et al European Journal of Cancer 42(2006):1083-1092 抑那通3.75mg預(yù)充式注射器 現(xiàn)有劑型現(xiàn)有劑型 上市新劑型上市新劑型 AUA(2010)內(nèi)分泌治療新進(jìn)展

34、 Sarcopenia in men receiving androgen deprivation therapy for prostate cancer: a prospective 3-year study. Matthew R. Smith,CA. AUA(2010)內(nèi)分泌治療新進(jìn)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,

35、 and 36 months. AUA(2010)內(nèi)分泌治療新進(jìn)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