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: 8908163
• 负责人: Noah Robert Zanville
• 金额: $ 2.99万
• 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/8908163
• 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; Taxane Compound; 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; 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其跨学科、转化性研究计划所需的知识、培训和技能基础。这项研究的重点是开发测量接受化疗药物紫杉醇（Taxol(r)、Abraxane(r)）的乳腺癌幸存者（BCS）化疗引起的周围神经病变（CIPN）的工具。尽管紫杉醇对于治疗转移性和非转移性乳腺癌均非常有效，但接受该药物的 BCS 中 50-80% 的患者接触紫杉醇会导致 CI​​PN。 CIPN 对 BCS 的影响可能很严重；症状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、发挥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 可以提醒提供者注意 BCS 存在严重症状的风险，从而使提供者能够开始教学以尽量减少安全风险（例如跌倒、事故）并开始使用可用药物（例如度洛西汀、加巴喷丁）进行治疗。随着治疗的进展，准确监测 CIPN 可以帮助提供者确定是否需要推迟或停止化疗，并为团队提供帮助女性制定生存计划所需的信息。 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 的方法很难满足这些需求。评估 CIPN 的常用策略（如神经病变分级量表或自我报告问卷）可以有效地测量 CIPN 症状开始后的严重程度和类型，但无法检测到预测症状所需的 CIPN 早期体征，并且容易导致患者漏报。这些方法还缺乏针对特定类型神经损伤的能力。这对于 c 纤维来说尤其重要，c 纤维参与疼痛信号传导并且越来越多地 已被证明在 CIPN 的发展和延续中发挥着作用。最近的研究发现了一种准确、灵敏的测量 c 纤维神经病变的方法，有望用于检测和监测 BCS 中的 CIPN。该方法包括测量用热敏电阻刺激温度敏感神经（C 纤维）后流向皮肤的血流量增加情况。 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，这为临床上可行的 CIPN 检测和监测方法打开了大门。本研究的目的是确定轴突反射是否可用于准确测量每周接受紫杉醇的 BCS 的 c 纤维损伤 (CIPN)。