Effects of exercise during platinum chemotherapy on neuropathy: examining the interoceptive brain system and inflammation

项目摘要/摘要 化疗引起的周围神经病(CIPN)是一种严重的剂量限制性毒性，影响65%以上的 接受以铂为基础的化疗治疗胃肠道癌症的患者。CIPN不仅增加了 死亡率通过限制化疗剂量，CIPN通过麻木影响行走、写作、饮食和穿衣， 刺痛，疼痛，对冷敏感，手脚抽筋。目前还没有FDA批准的治疗方法 因为我们需要更多地了解CIPN的病理生理机制和CIPN的作用机制 治疗CIPN的前景看好。此外，大多数关于人体CIPN的研究都集中在紫杉烷类药物上。 乳腺癌患者的化疗。在这里，我们将重点放在患者的铂类化疗上 因为紫杉烷和铂诱导的CIPN都是非常常见的，但表现出 毒性的明显体征、症状和机制，对特定的治疗可能有不同的反应。这 该项目的动机是一种创新的观点，即CIPN症状不仅仅是由于周围神经 更确切地说，CIPN的症状会因大脑内感受性系统的损伤而恶化--这 处理来自身体的感觉-以及全身炎症。 这是一项第二阶段的随机临床试验，旨在评估白金期间12周锻炼的效果。 60例胃肠癌患者化疗对CIPN、内分泌和炎症的影响。具体的 本项目的目的是评估运动与营养教育(对照)在以下方面的效果：(1)患者报告 CIPN，(2)CIPN的临床评估(触觉敏感性和冷痛)，(3)内感(功能 感觉间大脑系统的连接性和自我报告)，以及(4)炎症(血清炎症 细胞因子)。 这是第一项研究在铂化疗期间运动对CIPN的影响，并检查 内感和炎症在铂诱导的CIPN治疗中的作用。这项研究的结果将 通知R01应用程序，以更明确地评估CIPN和练习的这一理论。如果这项工作成功了， 我们将找到一种有效的干预(练习)来缓解CIPN，我们将有一个更好的 了解运动如何缓解CIPN(即，内感和炎症)。我们相信这一知识 可用于通过锻炼或其他方式改善CIPN的预测、跟踪、分型和治疗 影响这些通路的干预措施。这最终将有助于减轻化疗对治疗的负担 癌症患者。

PROJECT SUMMARY/ABSTRACT Chemotherapy-induced peripheral neuropathy (CIPN) is a severe dose-limiting toxicity that affects over 65% of patients receiving platinum-based chemotherapy for gastrointestinal cancers. Not only does CIPN increase mortality by limiting the dose of chemotherapy, CIPN affects walking, writing, eating, and dressing via numbness, tingling, pain, cold sensitivity, and cramping in the hands and feet. There are no FDA-approved treatments for CIPN because we need a greater understanding of the pathophysiology of CIPN and mechanisms of action of promising treatments for CIPN. In addition, most research on CIPN in humans has focused on taxane-based chemotherapy in patients with breast cancer. Here, we are focusing on platinum-based chemotherapy in patients with gastrointestinal cancers because taxane- and platinum-induced CIPN are both very common but exhibit distinct signs, symptoms, and mechanisms of toxicities, and may respond differently to a given treatment. This project is motivated by an innovative perspective that CIPN symptoms are not due simply to peripheral nerve damage, but rather that CIPN symptoms are worsened by damage to the interoceptive brain system—which processes sensations from the body—as well as systemic inflammation. This is a Phase II randomized clinical trial to assess the effects of 12 weeks of exercise during platinum chemotherapy on CIPN, interoception, and inflammation in 60 patients with gastrointestinal cancer. The specific aims of this project are to assess the effects of exercise vs. nutrition education (control) on: (1) patient reported CIPN, (2) clinical assessments of CIPN (tactile sensitivity and cold-induced pain), (3) interoception (functional connectivity in the interoceptive brain system and self-report), and (4) inflammation (serum inflammatory cytokines). This is the first study to examine the effects of exercise during platinum chemotherapy on CIPN and to examine roles of interoception and inflammation in the treatment of platinum-induced CIPN. Results from this study will inform an R01 application to more definitively assess this theory of CIPN and exercise. If this work is successful, we will have identified an effective intervention (exercise) for alleviating CIPN and we will have a better understanding of how exercise alleviates CIPN (i.e., interoception and inflammation). We believe this knowledge can be applied to improve prediction, tracking, sub-typing, and treatment of CIPN using exercise or other interventions that affect these pathways. This will ultimately help alleviate the burden of chemotherapy on treating patients with cancer.