Randomized Placebo Controlled Trial of Bupropion for Cancer Related Fatigue

项目摘要 疲劳是癌症患者经历的最普遍和最令人痛苦的症状之一。治疗 癌症相关性疲劳的选择有限;其他疗法是研究的高度优先事项。他酮 自1999年以来已被确定为癌症相关疲劳的潜在疗法。安非他酮具有多种作用 靶向与癌症相关的疲劳相关的途径，包括炎症和下丘脑垂体 肾上腺（HPA）轴功能。安非他酮经细胞色素P 450 B6（CYP 2B 6）代谢， 广泛的特点。安非他酮的两项初步研究显示， 疲劳，但迄今为止还没有足够的动力，随机对照试验已经进行。的目标 目前的研究是进行第一个充分把握度，随机，双盲，安慰剂对照试验 安非他酮治疗癌症相关的疲劳因为疲劳在乳腺癌患者中很常见， 这项研究将侧重于这一群体。422例无病乳腺癌患者的样本， 将招募12-60个月前接受过化疗和/或放疗并报告明显疲劳的患者 通过罗切斯特大学癌症中心（URCC）国家癌症研究所社区肿瘤学 研究计划（NCORP）。受试者将以1：1的比例随机接受通用安非他酮XL或安慰剂。 将在随机化前和12周后评估疲劳。血液和唾液将被收集， 测量安非他酮代谢物、炎症、CYP 2B 6基因型和皮质醇（HPA轴的标志物 功能）。数据将用于解决以下目的：1）确定安非他酮与 安慰剂减轻疲劳的一项双盲、安慰剂对照、乳腺癌随机临床试验 疲劳幸存者; 2）评估安非他酮在疲劳乳腺癌幸存者中的耐受性，3） 探索安非他酮对癌症相关疲劳的假定机制的影响，以及4）探索 CYP 2B 6基因型与安非他酮代谢和疲劳变化的相关性。积极成果 目前的研究可能会彻底改变癌症相关疲劳的治疗，因为安非他酮安全，便宜， 广泛可用，并且可能比目前有限的治疗更容易被许多患者耐受和接受 选项.安非他酮对癌症相关性疲劳可能机制的影响 其他有效治疗的新途径。探索疗效的遗传调节因子可能有助于 确定哪些患者最有可能受益并调整剂量。

PROJECT SUMMARY Fatigue is one of the most prevalent and distressing symptoms experienced by cancer patients. Treatment options for cancer-related fatigue are limited; additional therapies are a high priority for research. Bupropion has been identified as a potential therapy for cancer-related fatigue since 1999. Bupropion has diverse actions that target pathways associated with cancer-related fatigue, including inflammation and hypothalamic pituitary adrenal (HPA) axis functioning. Metabolism of bupropion by cytochrome P 450 B6 (CYP2B6) has been extensively characterized. Two pilot studies of bupropion have shown promise in reducing cancer-related fatigue but to date no adequately-powered, randomized controlled trials have been conducted. The goal of the current study is to conduct the first adequately-powered, randomized, double-blinded, placebo-controlled trial of bupropion for cancer-related fatigue. Because fatigue is well-characterized in women with breast cancer, the study will focus on this population. A sample of 422 disease-free breast cancer patients who completed chemotherapy and/or radiotherapy 12-60 months previously and report significant fatigue will be recruited through the University of Rochester Cancer Center (URCC) National Cancer Institute Community Oncology Research Program (NCORP). Participants will be randomized 1:1 to receive generic bupropion XL or placebo. Fatigue will be assessed prior to randomization and 12 weeks later. Blood and saliva will be collected to measure bupropion metabolites, inflammation, CYP2B6 genotype, and cortisol (a marker for HPA axis functioning). Data will be used to address the following aims: 1) to determine the efficacy of bupropion versus placebo in reducing fatigue in a double-blinded, placebo-controlled, randomized clinical trial of breast cancer survivors with fatigue; 2) to assess the tolerability of bupropion in breast cancer survivors with fatigue, 3) to explore the effects of bupropion on putative mechanisms of cancer-related fatigue, and 4) to explore associations of CYP2B6 genotype with bupropion metabolism and changes in fatigue. Positive results from the current study could revolutionize the treatment of cancer-related fatigue, as bupropion is safe, inexpensive, widely-available, and may be more tolerable and acceptable for many patients than current, limited treatment options. Exploration of the effects of bupropion on putative mechanisms of cancer-related fatigue could open new avenues for additional efficacious treatments. Exploration of genetic moderators of efficacy could help identify which patients are most likely to benefit and tailor dosage.