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

项目总结/摘要 化疗引起的周围神经病变（CIPN）是一种严重的剂量限制性毒性， 接受铂类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，进食和穿衣， 刺痛、疼痛、冷敏感和手脚抽筋。没有FDA批准的治疗方法 CIPN，因为我们需要更好地了解CIPN的病理生理学和CIPN的作用机制。 有希望的治疗CIPN。此外，大多数关于人类CIPN的研究都集中在基于紫杉烷的 乳腺癌患者的化疗。在这里，我们关注的是以铂为基础的化疗在患者中的应用。 因为紫杉烷和铂诱导的CIPN都很常见，但表现出 不同的体征，症状和毒性机制，并可能对给定的治疗有不同的反应。这 该项目的动机是一个创新的角度，CIPN症状是不是由于简单的外周神经 损伤，而是CIPN症状因内感受性脑系统的损伤而恶化， 处理来自身体的感觉以及全身炎症。 这是一项II期随机临床试验，旨在评估铂治疗期间12周运动的效果。 化疗对60例胃肠道肿瘤患者CIPN、内感受和炎症的影响。具体 本项目的目的是评估运动与营养教育（对照）对以下方面的影响：（1）患者报告 CIPN，（2）CIPN的临床评估（触觉敏感性和冷诱发疼痛），（3）内感受（功能性 内感受性脑系统中的连通性和自我报告），和（4）炎症（血清炎症 细胞因子）。 这是第一个研究铂类化疗期间运动对CIPN的影响， 内感受和炎症在铂诱导的CIPN治疗中的作用。这项研究的结果将 通知R 01应用程序以更明确地评估CIPN和练习的此理论。如果这项工作成功， 我们将确定一个有效的干预（演习），以减轻CIPN，我们将有一个更好的 了解运动如何使CIPN变小（即，内感受和炎症）。我们相信这些知识 可以应用于使用锻炼或其他方法来改善CIPN的预测、跟踪、分型和治疗。 影响这些途径的干预措施。这将最终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.