Early Detection of Taxane-induced Neuropathy in Women with Breast Cancer

乳腺癌女性紫杉烷诱发神经病变的早期检测

• 批准号: 9149024
• 负责人: Noah Robert Zanville
• 金额: $ 3.03万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9149024
• 关键词: Abraxane; Accidents; Address; Adverse effects; Age; Antineoplastic Agents; Area; Axon; Blood Vessels; Blood flow; Breast Cancer survivor; C Fiber; Caliber; Chemotherapy-induced peripheral neuropathy; Data; Decision Making; Development; Diabetic Neuropathies; Dose; Early Diagnosis; Education; Educational process of instructing; Exposure to; Fiber; Fingers; Flare; Foundations; Health; Health Personnel; Heating; Injury; Knowledge; Life; Limb structure; Measurement; Measures; Mediating; Methods; Monitor; Nerve; Nerve Fibers; Neuropathy; Occupational; Outcome; Outcome Measure; Outcome Study; Paclitaxel; Pain; Patient Outcomes Assessments; Patient Self-Report; Patients; Pharmaceutical Preparations; Physical Function; Play; Provider; Quality of life; Questionnaires; Race; Reflex action; Research; Risk; Role; Safety; Sampling; Severities; Signal Transduction; Skin; Symptoms; Techniques; Temperature; Testing; Time; Toes; Training; Woman; afferent nerve; career; chemotherapy; daily functioning; duloxetine; effective therapy; falls; gabapentin; hereditary neuropathy; improved; malignant breast neoplasm; meetings; painful neuropathy; prevent; primary outcome; programs; public health relevance; skills; skills training; survivorship; symptom management; taxane; tool; tool development

 DESCRIPTION (provided by applicant): The proposed training plan will provide the applicant with the foundation of knowledge, training, and skills needed to begin his interdisciplinary, translational program of research. This research focuses on the development of tools for measuring chemotherapy-induced peripheral neuropathy (CIPN) in breast cancer survivors (BCS) who have received the chemotherapy drug paclitaxel (Taxol(r), Abraxane(r)). Although paclitaxel is highly effective as a treatment for both metastatic and non-metastatic breast cancer, exposure to paclitaxel leads to CIPN in 50-80% of BCS who receive the drug. The impact of CIPN on BCS can be severe; symptoms can interfere with occupational function and quality of life, and in some cases, force providers to stop potentially life-saving chemotherapy. Because of significant risk that CIPN symptoms pose to BCS' ability to complete treatment, function, and maintain quality of life, it is critical to identify CIPN as early as possible and monitor its progression carefully during treatment. Identifying CIPN as early as possible can alert providers to BCS at risk for severe symptoms, allowing providers to initiate teaching to minimize safety risks (e.g., falls, accidents) and initiate treatment with available agents (e.g., duloxetine, gabapentin). As treatment progresses, accurate monitoring of CIPN can help providers determine if chemotherapy needs to be delayed or discontinued and provide the team with information needed to help women plan for survivorship. Unfortunately, while early detection and accurate monitoring are important to managing CIPN effectively, current approaches to measuring CIPN are poorly suited to meet these needs. Common strategies for assessing CIPN like neuropathy grading scales or self-report questionnaires can be effective for measuring the severity and type of CIPN symptoms once they've started, but cannot detect the early signs of CIPN needed to predict symptoms and are vulnerable to patient underreporting. These approaches also lack the ability to target damage to specific types of nerves. This is especially important in the case of c-fibers, which are involved in pain signaling and increasingly have been shown to play a role in the development and perpetuation of CIPN. Recent studies have identified an accurate, sensitive approach for measuring c-fiber neuropathy that holds promise for detecting and monitoring CIPN in BCS. The approach involves measuring the increase in blood flow to the skin after stimulating temperature-sensitive nerves (c-fibers) with a heat probe (which is known as an axon reflex). Axon reflexes can be stimulated in as short a time as 20 minutes using simple heat probes, opening the door to a clinically feasible method for detecting and monitoring CIPN. The purpose of this study is to determine if axon reflexes can be used to accurately measure c-fiber damage (CIPN) in BCS receiving weekly paclitaxel.

 描述（由申请人提供）：拟议的培训计划将为申请人提供开始他的跨学科，翻译研究计划所需的知识，培训和技能的基础。本研究的重点是开发用于测量接受化疗药物紫杉醇（Taxol（r），Abraxane（r））的乳腺癌幸存者（BCS）化疗诱导的周围神经病变（CIPN）的工具。虽然紫杉醇作为转移性和非转移性乳腺癌的治疗非常有效，但暴露于紫杉醇导致50-80%接受该药物的BCS中的CIPN。CIPN对BCS的影响可能很严重;症状可能会干扰职业功能和生活质量，在某些情况下，迫使提供者停止可能挽救生命的化疗。由于CIPN症状对BCS完成治疗、功能和维持生活质量的能力构成重大风险，因此尽早识别CIPN并在治疗期间仔细监测其进展至关重要。尽早识别CIPN可以提醒提供者BCS有严重症状的风险，允许提供者启动教学以最大限度地减少安全风险（例如，福尔斯、事故）并开始用可用的药剂进行治疗（例如，度洛西汀、加巴喷丁）。随着治疗的进展，CIPN的准确监测可以帮助提供者确定是否需要延迟或停止化疗，并为团队提供帮助妇女计划生存所需的信息。 不幸的是，虽然早期检测和准确监测对于有效管理CIPN很重要，但目前测量CIPN的方法不适合满足这些需求。用于评估CIPN的常见策略，如神经病变分级量表或自我报告问卷，一旦开始就可以有效地测量CIPN症状的严重程度和类型，但无法检测到预测症状所需的CIPN早期体征，并且容易受到患者漏报的影响。这些方法也缺乏针对特定类型神经的损伤的能力。这在c纤维的情况下尤其重要，c纤维参与疼痛信号传导，并且越来越多地参与疼痛信号传导。 已被证明在CIPN的发展和延续中发挥作用。最近的研究已经确定了一种准确，灵敏的方法来测量C纤维神经病变，有望检测和监测BCS中的CIPN。该方法涉及用刺激温度敏感神经（c纤维）后测量皮肤血流量的增加 热探针（称为轴突反射）。使用简单的热探针可以在短至20分钟的时间内刺激轴突反射，从而为临床上可行的检测和监测CIPN的方法打开了大门。本研究的目的是确定轴突反射是否可用于准确测量接受每周紫杉醇治疗的BCS患者的C纤维损伤（CIPN）。