Internet-Assisted Cognitive Behavior Intervention for Targeted Therapy Fatigue

描述(申请人提供)：靶向治疗是新一代药物，旨在干扰对肿瘤生长和进展至关重要的分子靶点。第一个也是最成功的例子之一是为慢性粒细胞白血病(CML)开发的口服药物伊马替尼。尽管伊马替尼和类似药物的耐受性比他们取代的方案要好得多，但它们仍然存在副作用，这些副作用会困扰患者，干扰生活质量，并导致依从性问题。由于治疗通常持续多年，而且可能是终生的，有效的副作用管理至关重要。最近的研究表明，疲劳是接受口服靶向治疗的CML患者最常见和最令人烦恼的症状。这项拟议的研究是解决靶向治疗相关疲劳(TTF)问题的第一次系统性尝试。为此，它建立在之前的研究基础上，该研究表明，一种基于症状演变的沉淀-持久模型的认知行为疗法(CBT)对完成治疗(即癌症后疲劳或PCF)且没有临床疾病证据的癌症患者非常有效。因此，与其开发者合作，我们将调整CBT-PCF，这是一种基于针对完成治疗的疲劳患者的沉淀-永续模式的干预措施，以开发CBT-TTF，这是一种基于修订的针对维持靶向治疗的疲劳患者的催促-加重模式的干预措施。采用最初干预的定制模块方法，我们将首先对疲惫的CML患者和CML护理提供者进行迭代定性研究，以确定哪些CBT-PCF模块需要保留和调整，并根据概念模型确定潜在的新模块来开发。适应还包括从基于诊所的交付转向使用可视电话和平板电脑技术(使用iPad的FaceTime)的互联网辅助交付，以将旅行负担降至最低，最大限度地提高便利性，并培养更大的传播潜力。一旦开发出来，CBT-TTF将在一项小规模随机对照试验中，对口服靶向治疗的疲倦CML患者进行可行性、可接受性和潜在疗效的评估，而不是常规治疗。具体目的是：1)开发互联网辅助形式的CBT for TTF(CBT-TTF)，以经验支持的CBT形式有效地对抗治疗后癌症相关疲劳为基础；2)评估CBT-TTF和相关方法的可行性和可接受性；3)探索CBT-TTF在减少疲劳方面的有效性(主要结果)；以及4)探索CBT-TTF在改善生活质量和口服用药依从性(次要结果)方面的有效性。这项研究的成功完成将为一项更大规模的多中心临床试验提供坚实的基础，预计将产生一种高效且易于传播的干预措施，解决目标疗法正在将癌症从威胁生命的疾病转变为慢性病的日益增长的患者群体中的主要治疗后果。

DESCRIPTION (provided by applicant): Targeted therapies are a new generation of drugs designed to interfere with molecular targets critical for tumor growth and progression. One of the first and most successful examples is the oral medication imatinib developed for chronic myelogenous leukemia (CML). Although imatinib and similar medications are much better tolerated than regimens they replaced, they still possess side effects that are bothersome to patients, interfere with quality of life, and contribute to problems with adherence. Since treatment typically continues on a daily basis for many years and may be life-long, effective management of side effects is critically important. Recent studies show that fatigue is the most common and bothersome symptom identified by CML patients being treated with oral targeted therapy. The proposed research represents the first systematic attempt to address the problem of targeted therapy-related fatigue (TTF). Toward this end, it builds on previous research showing that a form of cognitive behavior therapy (CBT) based on a precipitating-perpetuating model of symptom evolution is highly effective against fatigue in cancer patients with no clinical evidence of disease who have completed treatment (i.e., post-cancer fatigue or PCF). Accordingly, in collaboration with its developers, we will adapt CBT-PCF, an intervention based on the precipitating-perpetuating model for fatigued patients who completed treatment, to develop CBT-TTF, an intervention based on a revised precipitating-exacerbating model for fatigued patients on maintenance targeted therapy. Adopting the tailored modular approach of the original intervention, we will first conduct iterative qualitative research with fatigued CML patients and CML care providers to determine which CBT-PCF modules to retain and adapt and to identify potential new modules to develop based on the conceptual model. The adaptation also involves moving from clinic-based delivery to Internet-assisted delivery using video telephony and tablet computer technology (FaceTime using iPads) in order to minimize travel burden, maximize convenience, and foster greater dissemination potential. Once developed, CBT-TTF will be evaluated with fatigued CML patients on oral targeted therapy for feasibility, acceptability and potential efficacy relative to usual care only in a small-scale randomized controlled trial. The specific aims are to: 1) develop an Internet-assisted form of CBT for TTF (CBT-TTF) using as a foundation an empirically-supported form of CBT effective against post-treatment cancer-related fatigue; 2) evaluate CBT-TTF and related methods for feasibility and acceptability; 3) explore the efficacy of CBT-TTF in reducing fatigue (primary outcome); and 4) explore the efficacy of CBT-TTF in improving quality of life and oral medication adherence (secondary outcomes). Successful completion of this research will provide a strong foundation for a larger multi-center clinical trial expected to yield a highly effective and readily disseminale intervention that addresses a major treatment consequence in the growing population of patients for whom target therapies are transforming cancer from a life-threatening illness to a chronic illness.