抑那通治疗前列腺癌的最新进展

1、抑那通治疗前列腺癌的新进展黄 毅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,

2、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 t

3、his 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

4、same ADT combined with RT starting within 3 months over 7 weeks.AUA(2010)内分泌治疗新进展RESULTSAUA(2010)内分泌治疗新进展 Prevalence of metabolic syndrome in prostate cancer patients under androgen deprivation therapy: interim results of a case-control study. Jorge Ropero, Barcelone, Spain.AUA(2010)内分泌治疗新进展INTRODUC

5、TION AND OBJECTIVES Cardiovascular mortality is the most important cause of death in patients with prostate cancer (PC). The development of metabolic syndrome (MS) in patients undergoing androgen deprivation therapy (ADT) has been related with this increase in mortality rate. The aim of this study h

6、as been to confirm the hypothesis that ADT increases the prevalence of MS.AUA(2010)内分泌治疗新进展METHODS A group of 157 patients were enrolled in this interim analysis of a prospective case control study. 53 PC patients under ADT during a mean time of 52 months (6 to 252) and 104 age matched controls eval

7、uated at the time of prostate biopsy (52 with cancer and 52 without) were included.AUA(2010)内分泌治疗新进展METHODS MS was analyzed according the ATPIII panel criteria: Fasting plasma glucose level 110 mg/dL serum triglyceride level 150 mg/dL serum high-density lipoprotein level102 cm Blood pressure of 130/

8、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

9、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

10、Hoo Park, KoreaAUA(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 thic

11、kness, 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 canc

12、er 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RESULTSThere are no significant changes in hemoglobin and cholesterol levels.AU

13、A(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 per

14、iodically 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 dep

15、rivation 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 i

16、n 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

17、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

18、 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

19、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 decreas

20、ed 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 prosp

21、ective trial. Matthew McIntyre, Charleston, SCAUA(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

22、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 testoster

23、one 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 ho

24、rmones 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

25、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；

26、 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 lin

27、e 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, an

28、d 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

29、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 quali

30、ty 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 12周 时 亮 丙 瑞 林 的 有 效 率 （ CR+PR） 如 下 ， 在 批 准

31、 上 市 时 为 53.9%， 在 市 场 销 售 后 的 调 查 成 绩 为 81.2%。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 tableS tableN CN CP DP D10 268 153 .981 .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 3.75mg批 准 上 市 时病灶 有效率（%）CR+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