Feasibility of an Exercise and Dietary Intervention in Men on Prolonged ADT

描述(申请人提供)：雄激素剥夺疗法是男性转移性前列腺癌(PC)治疗的基础，现在经常被纳入治疗局部晚期PC的多种治疗策略。不幸的是，ADT的分解代谢效应导致了显著的发病率，包括瘦肌肉质量的损失，脂肪质量的增加，肌肉力量的降低和骨密度的降低。反过来，ADT的这些不利影响与功能衰退和虚弱有关。新出现的证据还表明，服用ADT的男性患心血管疾病和代谢综合征的风险更高。因此，越来越清楚的是，PC患者在身体功能、健康状况和生活质量(QOL)方面承受着长期和挥之不去的影响，这些影响伴随着ADT作为更有效的癌症控制和延长寿命的“权衡”。有人提出，改变生活方式，包括改变锻炼和饮食行为，可能会抵消甚至逆转长期服用ADT带来的不良影响。随着临床上越来越多地关注提高癌症存活率的生活质量，迫切需要确定能够有效抵消ADT的不利影响并将接受治疗的PC患者的功能下降和慢性病风险降至最低的生活方式干预措施。我们的长期研究目标是开发创新和有效的生活方式干预措施，用于治疗接受长期ADT的PC患者。然而，证明基于理论的个性化运动和饮食干预对改善男性ADT延长的功能限制、慢性病风险因素和生活质量的有效性的经验证据是有限的。此外，生活方式、运动和饮食干预在这些临床相关结果中产生改善的途径尚未确定。我们的中心假设是：1)理论驱动的、个性化的锻炼和饮食干预将比标准护理治疗方法在功能限制、身体成分和生活质量方面产生更好的改善，2)功能限制和生活质量的干预效果将通过改善自我效能信念和中间残疾过程模型结果而间接操作。目前应用的目的是确定运动和饮食干预对接受ADT的PC患者的功能、疾病和生活质量结果的可行性和初步疗效。在这项调查完成后，我们发现的主要积极影响将是基于证据的科学验证，即生活方式、锻炼和饮食干预在预防和治疗长期ADT对PC患者的不良影响方面的有效性。这项拟议的调查有可能迅速影响医学界及其对ADT的处理方法。如果个性化的锻炼和饮食调整方法改善了结果，我们将有必要的证据来改变目前男性ADT的临床实践。

DESCRIPTION (provided by applicant): Androgen-deprivation therapy is the foundation of treatment for men with metastatic prostate cancer (PC) and is now frequently incorporated into multimodality strategies for the curative treatment of locally advanced PC. Unfortunately, the catabolic effects of ADT result in significant morbidity including loss of lean muscle mass, increased fat mass, reduced muscle strength, and lower bone mineral density. In turn, these adverse effects of ADT are linked with functional decline and frailty. Emerging evidence also suggests that men on ADT are at greater risk for cardiovascular disease and the onset of metabolic syndrome. Thus, it is becoming increasingly clear that PC patients endure long and lingering impacts on physical function, health status, and quality of life (QOL) that accompany ADT as a "trade-off" for more effective cancer control and extended longevity. It has been proposed that lifestyle modification, including change in exercise and dietary behaviors, may offset, or even reverse, the adverse effects that accompany long-term administration of ADT. With a growing clinical focus upon improvements in QOL in cancer survivorship, there is a critical need to identify lifestyle interventions that are effective in offsetting the adverse effets of ADT and minimizing the risk of functional decline and chronic disease in PC patients undergoing treatment. Our long term research goal is to develop innovative and effective lifestyle interventions for the treatment of PC patients undergoing prolonged ADT. However, empirical evidence documenting the efficacy of theory-based, personalized exercise and dietary interventions for improving functional limitations, chronic disease risk factors, and QOL in men on prolonged ADT is limited. Additionally, the pathways through which lifestyle, exercise, and dietary interventions produce improvements in these clinically relevant outcomes have yet to be defined. Our central hypotheses are that: 1) a theory-driven, personalized exercise and dietary intervention will produce superior improvements in functional limitations, body composition, and quality of life relative to a standard of care treatment approach and 2) the intervention effects o functional limitations and QOL will be indirect operating through improvements in self-efficacy beliefs and intermediate disablement process model outcomes. The objective for this current application is to determine the feasibility and preliminary efficacy of an exercise and dietary intervention upon functional, disease, and QOL outcomes in PC patients undergoing ADT. Upon completion of this investigation, the primary positive impact of our findings would be evidence-based scientific verification of the efficacy of lifestyle, exercise, and dietary interventions in prevention and treatment of the adverse effects of prolonged ADT in PC patients. This proposed investigation has the potential to rapidly impact the medical community and their approach to ADT. Should the personalized approach to exercise and dietary modification improve outcomes, we will have the evidence necessary to alter current clinical practice of men on ADT.