ADAM: Androgen Deprivation vs. Antiandrogen Monotherapy

描述（由申请方提供）：本项目的广泛长期目的是在非转移性前列腺癌男性患者中比较比卡鲁胺单药治疗与使用促性腺激素释放激素（GnRH）激动剂的雄激素剥夺治疗（ADT）的不良反应。GnRH激动剂占前列腺癌治疗医疗保险总支出的三分之一GnRH激动剂的不良反应包括骨密度降低（BMD），骨折风险增加，身体成分变化，包括肌肉大小和力量减少。比卡鲁胺（Casodex（R））是一种正在开发的外周选择性非甾体抗雄激素药物，可作为早期前列腺癌的辅助治疗和ADT的替代药物。比卡鲁胺的不良反应可能比GnRH激动剂少，因为它（1）增加而不是降低血清睾酮和雌激素水平，（2）保留患者报告的体能。本项目的具体目的是比较比卡鲁胺单药治疗与GnRH激动剂单药治疗对BMD、肌肉大小和力量的影响。这些具体目标将通过一项共同协议来实现。该研究将包括患有局部晚期、淋巴结阳性或复发性前列腺癌并且没有骨转移的放射学证据的男性。受试者将被随机分配接受亮丙瑞林或比卡鲁胺（每日口服150 mg）治疗12个月。在0、6和12 BMD时通过双能X线吸收测定法（DXA）和定量计算机断层扫描（QCT）评价以下结局，通过QCT评价大腿和腹部的横截面肌肉和脂肪面积，通过人体测量法、生物阻抗、DXA和同位素稀释法评价身体组成，通过最大随意力量和Margada功率测试评价肌肉功能，以及生活质量。该项目将提供有关GnRH激动剂和比卡鲁胺对骨密度、肌肉大小和强度影响的明确数据，并将影响前列腺癌男性的临床管理。该项目可能证明比卡鲁胺单药治疗的优势，或可能强调开发更具选择性药物的必要性。此外，该项目将提供重要的见解睾酮和雌激素在骨代谢中的相对贡献，以及老年男性肌肉大小和力量的维持。

DESCRIPTION (provided by applicant): The broad long-term objective of this project is to compare the adverse effects of bicalutamide monotherapy with androgen deprivation therapy (ADT) using a gonadotropin-releasing hormone (GnRH) agonist in men with nonmetastatic prostate cancer. GnRH agonists account for one-third of total Medicare expenditures for prostate cancer treatment Adverse effects of GnRH agonist include decreased bone mineral density (BMD), increased fracture risk, changes in body composition including decreased muscle size and strength. Bicalutamide (Casodex(R) is a peripherally selective, nonsteroidal antiandrogen under development as adjuvant therapy for early stage prostate cancer and as an alternative to ADT. Bicalutamide might have fewer adverse effects than GnRH agonists because it (1) increases rather than decreases serum testosterone and estrogen levels, (2) preserves patient-reported physical capacity. The specific aims of this project are to compare the effects of bicalutamide monotherapy versus GnRH agonist monotherapy on BMD and muscle size and strength. These specific aims will be accomplished using a common protocol. The study will include men with locally advanced, node-positive, or recurrent prostate cancer and no radiographic evidence of bone metastases. Subjects will be randomly assigned to leuprolide or bicalutamide (150 milligrams by mouth daily) for 12 months. The following outcomes will be evaluated at 0, 6, and 12 BMD by dual energy x-ray absorptiometry (DXA) and quantitative computed tomography (QCT), cross-sectional muscle and fat areas of the thigh and abdomen by QCT, body composition by anthropometry, bioimpedance, DXA, and isotope dilution, muscle function by maximum voluntary strength and Margada power testing, and quality of life. This project will provide definitive data about effects of GnRH agonists and bicalutamide on bone mineral density and muscle size and strength, and will impact the clinical management of men with prostate cancer. This project may demonstrate advantages of bicalutamide monotherapy or may highlight the need for development of more selective agents. In addition, this project will provide important insights into the relative contributions of testosterone and estrogen in bone metabolism, and maintenance of muscle size and strength in older men.