A Combination Therapy to Treat Cancer-Related Fatigue

项目总结 癌症相关性疲劳(CRF)是前列腺癌最常见和最令人衰弱的症状。 在根治性治疗期间和之后的患者-放射治疗(RT)和雄激素剥夺治疗(ADT)，以及 对患者的身体、心理、社会、职业功能和整体素质产生不利影响 然而，目前的治疗方案未能令人满意地缓解慢性肾功能衰竭。练习(EX)和 到目前为止，哌醋甲酯(MP)是治疗CRF研究最多、最有益的疗法，但两者都只有 影响不大。根据初步数据显示，EX加MP的组合是可行的，并可能 为了有效地减少CRF，拟议的研究将解决以下指导性假设：结合EX 使用随机安慰剂对照试验，加用MP将导致疲劳的更有力的改善。这个 主要目的是确定EX+MP的联合治疗是否优于EX+安慰剂 前列腺癌患者行去雄激素治疗后CRF的变化 12周(目标1)。CRF将使用函数中的曲线下面积(AUC)进行测量 评估慢性病治疗-疲劳(Facit-F)子量表以检验组合的假设 与运动加安慰剂相比，EX加MP可导致CRF的更大程度的降低。要解决这个问题 假设EX加MP的组合将导致额外的CRF相关措施的改善， EX加MP对生活质量的影响(使用癌症治疗总体功能评估)， 睡眠障碍(使用匹兹堡睡眠质量指数和多维疲劳症状 清单)、睡眠/清醒时间活动(活动记录仪)、焦虑和抑郁情绪(使用医院焦虑和 抑郁程度)、身体功能(使用通常的步速、30秒的椅子站立测试和握手 体力)、心肺适合度(最大摄氧量)、炎症(C反应蛋白)和认知测量将 被评估(目标2)。为了解决这样的假设，即哌醋甲酯和运动的结合将 有超过单独运动或单独使用哌醋甲酯降低CRF的协同效应， EX和MP的潜在协同效应将通过测量所有四个手臂的Facit-F AUC来评估， 从而告知模型EX和MP如何相互作用(目标3)。最后，大脑活动的差异 应答者和非应答者之间的EX加MP干预将使用 脑电(EEG)(AIM 4)，以识别CRF的新生物标志物并提供新的模型 集成基础CRF及其维度，以响应EX和/或MP。创新地利用现有的 技术，结合针对特定和明确定义的患者群体的CRF的新方法， 可以为CRF的安全、可行和有效的治疗提供证据，并将产生新的和高度的 有关CRF的可解释数据构成了在理解和治疗疲劳方面向前迈出的重要一步。

PROJECT SUMMARY Cancer-related fatigue (CRF) is the most frequent and debilitating symptom experienced by prostate cancer patients during and after curative treatment-radiotherapy (RT) and androgen deprivation therapy (ADT), and has detrimental effects on patients' physical, psychological, social, occupational functioning and overall quality of life; however, current treatment options fail to satisfactorily alleviate CRF. Exercise (EX) and Methylphenidate (MP) are by far the most investigated and beneficial therapies for CRF, but both have only modest effects. Based on preliminary data suggesting that the combination of EX plus MP is feasible and may be efficacious in reducing CRF, the proposed research will address the guiding hypothesis that combining EX plus MP will result in a more robust improvement of fatigue using a randomized placebo-controlled trial. The primary objective is to determine if the combination of EX + MP is superior to EX plus placebo in the treatment of CRF in patients with prostate cancer scheduled to receive radiotherapy with androgen deprivation therapy for 12 weeks (Aim 1). CRF will be measured using the area under the curve (AUC) in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) subscale to test the hypothesis that the combination of EX plus MP will result in a greater reduction of CRF compared with exercise plus placebo. To address the hypothesis that the combination of EX plus MP will result in improvements in additional CRF-related measures, the effects of EX plus MP on quality-of-life (using the Functional Assessment of Cancer Therapy – General), sleep disturbance (using the Pittsburgh Sleep Quality Index and the Multidimensional Fatigue Symptom Inventory), sleep/wake time activity (actigraphy), anxiety and depressed mood (using the Hospital Anxiety and Depression Scale), physical function (using usual gait speed, the 30-second chair stand test, and hand grip strength), cardiorespiratory fitness (VO2 max), inflammation (C-reactive protein), and cognitive measures will be assessed (Aim 2). To address the hypothesis that the combination of methylphenidate plus exercise will have synergistic effects that exceed the reduction in CRF by either exercise alone or methylphenidate alone, potential synergistic effects of EX and MP will be evaluated by measuring the FACIT-F AUC in all four arms, thus informing a model of how EX and MP may interact together (Aim 3). Finally, differences in brain activity between responders and non-responders to the EX plus MP intervention will be explored using electroencephalography (EEG) (Aim 4) in order to identify novel biomarkers of CRF and to inform a new model integrating underlying CRF and its dimensions in response to EX and/or MP. The innovative use of existing technologies, combined with a novel approach to CRF targeting a specific and well-defined patient population, could provide evidence for a safe, feasible, and effective treatment for CRF, and will yield new and highly interpretable data on CRF constituting a significant step forward in the understanding and treatment of fatigue.