ADAM: Androgen Deprivation vs. Antiandrogen Monotherapy

描述（由申请人提供）：本项目的长期目标是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）对非转移性前列腺癌患者的不良反应。GnRH激动剂占前列腺癌治疗总医疗费用的三分之一。GnRH激动剂的不良反应包括降低骨密度（BMD），增加骨折风险，改变身体组成，包括肌肉大小和力量的减少。Bicalutamide （Casodex）是一种外周选择性非甾体抗雄激素，正在开发用于早期前列腺癌的辅助治疗和ADT的替代品。比卡鲁胺可能比GnRH激动剂有更少的副作用，因为它(1)增加而不是降低血清睾酮和雌激素水平，(2)保留患者报告的身体能力。该项目的具体目的是比较比卡鲁胺单药治疗与GnRH激动剂单药治疗对骨密度、肌肉大小和力量的影响。这些具体的目标将通过一个共同的协议来实现。该研究将包括局部晚期、淋巴结阳性或复发性前列腺癌且无骨转移影像学证据的男性。受试者将被随机分配到leuprolide或bicalutamide组（每日口服150毫克），持续12个月。以下结果将通过双能x线吸收仪（DXA）和定量计算机断层扫描（QCT）在骨密度为0,6和12时进行评估，通过QCT评估大腿和腹部的横断面肌肉和脂肪区域，通过人体测量测量身体成分，生物阻抗，DXA和同位素稀释，通过最大自主力量和Margada功率测试评估肌肉功能，以及生活质量。该项目将提供GnRH激动剂和比卡鲁胺对骨密度、肌肉大小和力量影响的明确数据，并将影响前列腺癌男性的临床管理。该项目可能会证明比卡鲁胺单药治疗的优势，或者可能会强调开发更具选择性的药物的必要性。此外，该项目将为睾酮和雌激素在老年男性骨代谢、肌肉大小和力量维持中的相对贡献提供重要见解。

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.