A Randomized Controlled Trial of Dexamethasone for Dyspnea in Cancer Patients

项目总结 呼吸困难是与癌症有关的最常见和最令人痛苦的症状之一，近70%的人会出现呼吸困难 晚期癌症和胸腔内恶性肿瘤的患者。呼吸困难与功能受损有关， 生活质量下降，生存时间缩短。目前治疗呼吸困难的方法，如补充氧气 和阿片类药物，提供有限的缓解。尽管呼吸困难比疼痛更难治疗，但很少有临床试验 已经进行了呼吸困难的治疗，迫切需要这样的试验来改善中国的生活质量 患有这种疾病的癌症患者。我们研究的长期目标是开发基于证据的 癌症患者呼吸困难的姑息治疗。 皮质类固醇可能通过调节炎症反应改善呼吸困难的感觉。 中枢和外周反应，消肿消肿。根据我们最近一次调查的初步数据 临床试验中，我们假设大剂量地塞米松治疗癌症相关性呼吸困难是有效的。这个 拟议的双臂、双盲、平行(2：1)随机对照试验的总体目标是比较 地塞米松与安慰剂治疗癌性呼吸困难的疗效比较。这样做的主要具体目的是 研究是比较1周时地塞米松组和安慰剂组的呼吸困难强度。 在第二个具体目标中，我们将比较地塞米松和安慰剂在以下方面的效果 个性化的呼吸困难反应(基于个性化的呼吸困难目标)、呼吸困难的不适、其他 第1周和第1周的症状、健康相关生活质量、呼吸生理功能和不良反应 2，以及第二周呼吸困难的强度。第三个目标是确定呼吸困难的预测性标志物 对地塞米松的反应。在获得代孕同意后，我们将随机选择患者接受 地塞米松或安慰剂每日两次，连续2周，并密切监测患者。 拟议的研究具有创新性，因为它将涵盖一组新的适应症(即强度和 呼吸困难)、患者群体(即癌症患者)、预测指标(即炎症性 生物标志物、呼吸生理功能)和患者报告的结果测量(即，个性化 呼吸困难反应，不良事件通用术语标准的患者报告结果版本 地塞米松)。拟议研究的预期结果是将地塞米松确定为 一种治疗癌症患者呼吸困难的方法。这些结果有望在临床上产生重要的积极作用。 效果是因为对呼吸困难的有效管理将有助于提高患者的生活质量。这项研究将 也增加了我们对呼吸困难的病理生理学的基本了解，例如地塞米松是如何 改善炎症和呼吸生理参数，这可能使我们设计出新的和更多的 对这种令人痛苦的症状进行有效的个性化治疗，最终推动了呼吸困难研究领域的发展 推进和转变治疗模式。

PROJECT SUMMARY Dyspnea is one of the most common and distressing symptoms associated with cancer, occurring in nearly 70% of patients with advanced cancer and intrathoracic malignancies. Dyspnea is associated with impaired function, decreased quality of life, and shortened survival. Current therapies for dyspnea, such as supplemental oxygen and opioids, provide limited relief. Although dyspnea is more difficult to treat than pain is, few clinical trials of therapies for dyspnea have been conducted, and such trials are urgently needed to improve quality of life in cancer patients suffering from this condition. The long-term goal of our research is to develop evidence-based palliative therapies for dyspnea in patients with cancer. Corticosteroids may potentially improve the sensation of dyspnea by modulating the inflammatory response centrally and peripherally and decreasing swelling. On the basis of our preliminary data from a recent clinical trial, we hypothesize that high-dose dexamethasone is effective in treating cancer-related dyspnea. The overall objective of the proposed two-arm, double-blind, parallel (2:1), randomized, controlled trial is to compare the effect of dexamethasone with that of placebo on cancer-related dyspnea. The primary specific aim of this study is to compare the intensity of dyspnea in the dexamethasone arm with that in the placebo arm at week 1. In the second specific aim, we will compare the effects of dexamethasone with those of placebo in terms of personalized dyspnea response (based on a personalized dyspnea goal), unpleasantness of dyspnea, other symptoms, health-related quality of life, respiratory physiologic function, and adverse effects at week 1 and week 2, as well as the intensity of dyspnea at week 2. The third aim is to identify predictive markers of dyspnea response to dexamethasone. After obtaining surrogate consent, we will randomize patients to receive either dexamethasone or placebo twice daily for 2 weeks and monitor the patients closely. The proposed study is innovative in that it will cover a novel set of indications (i.e., both intensity and unpleasantness of dyspnea), patient population (i.e., patients with cancer), predictive makers (i.e., inflammatory biomarkers, respiratory physiologic function), and patient-reported outcome measures (i.e., personalized dyspnea response, Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events instrument) for dexamethasone. The expected outcome of the proposed study is to establish dexamethasone as a treatment for dyspnea in patients with cancer. These results are expected to have an important positive clinical effect because the effective management of dyspnea will help improve patients' quality of life. This study will also increase our fundamental understanding of the pathophysiology of dyspnea, such as how dexamethasone improves inflammation and respiratory physiologic parameters, which may allow us to devise new and more effective, personalized treatments for this distressing symptom, ultimately moving the field of dyspnea research forward and shifting the treatment paradigm.