Flexible versus Standard Aerobic Training Dosing in Primary Breast Cancer: A Randomized and Response-Adapted Trial

项目摘要/摘要 原发性乳腺癌化疗导致心肺功能(CRF)显著下降 使患者的症状负担增加，癌症的发病率和死亡率增加 以及非癌症的情况。随机试验证明在化疗期间进行有氧训练是可行的 用于治疗原发性乳腺癌，并减轻CRF中治疗诱导的损害。然而，我们最近的发现 表明即使在化疗期间和化疗后进行AT，CRF仍然显著低于正常值， 只有不到25%的患者有临床上有意义的CRF反应。大幅增加AT的剂量 增加CRF反应；然而，较高的AT剂量与较低的AT依从性相关。因此，使用 将患者分配到固定剂量的传统剂量-反应设计可能是轻率的 较低的固定AT剂量将导致一些患者剂量不足，而另一些患者依从性较差。一个更有耐心的人- 药物试验中使用的中心方法是灵活的剂量，即每个患者的剂量在耐受时递增。 目前还没有直接评估灵活的AT剂量治疗CRF在任何癌症环境中的疗效的试验。至 解决运动-肿瘤学研究中的这一基本知识差距，本研究的目标是 比较灵活的固定AT剂量和标准固定AT剂量以及反应适应AT对CRF反应的影响。在……里面 这项随机试验，总共140名不活跃(90分钟中等强度运动/周)的患者 计划开始化疗的乳腺癌将随机分配(1：1)灵活剂量：个人 剂量增加；或标准固定剂量：每周90分钟，持续约32周(化疗期间和化疗后)。 32周后无反应(3.50毫升/公斤/分钟CRF改善)的患者将完成20周的 扩展的灵活剂量AT。我们将解决3个具体目标：目标1：比较灵活与 标准剂量对CRF有效率的影响。目标2：确定对依从性、安全性和患者报告的影响 结果。目的3：评价扩张型AT治疗慢性肾功能衰竭无反应者的疗效。影响：这项研究面临挑战 目前的教条是所有患者对固定的AT剂量反应相同，并将首先评估灵活的AT 在任何癌症人群中使用剂量。接受癌症治疗不是结构化AT的资格条件， 因此，AT目前并不被认为是癌症治疗的标准方面。我们期待着拟议的 试验将通过确定最大限度提高CRF应答率的AT方案来直接解决未满足的临床需求 如果成功，这项研究的结果将有助于指导AT方案转化为临床治疗。

PROJECT SUMMARY/ABSTRACT Chemotherapy for primary breast cancer causes significant declines in cardiorespiratory fitness (CRF) predisposing patients to increased symptom burden and increased risk of morbidity and mortality from cancer and non-cancer conditions. Randomized trials demonstrate aerobic training (AT) is feasible during chemotherapy for primary breast cancer and attenuates treatment-induced impairments in CRF. However, our recent findings indicate that even with AT during and after chemotherapy, CRF remains substantially below normative values, and less than 25% of patients have a clinically meaningful CRF response. Increasing the dose of AT substantially increases CRF response; however, higher AT doses are associated with lower AT adherence. Thus, use of a conventional dose-response design wherein patients are assigned to fixed doses is likely imprudent considering lower fixed AT doses will result in underdosing in some patients, and poor adherence in others. A more patient- centered approach used in drug trials is flexible dosing, where the dose is escalated for each patient as tolerated. There have been no trials directly assessing the efficacy of flexible AT dosing on CRF in any cancer setting. To address this fundamental knowledge gap in exercise-oncology research, the objective of this study is to compare the effects of flexible versus standard fixed AT dosing and response-adapted AT on CRF response. In this randomized trial, a total of 140 inactive (<90 mins of moderate-intensity exercise/wk) patients with primary breast cancer scheduled to initiate chemotherapy will be randomly allocated (1:1) to Flexible dosing: Individual AT doses escalated; or Standard fixed dosing: 90 mins/week for ~32 weeks (during and after chemotherapy). Patients who do not respond (<3.50 ml/kg/min CRF improvement) at 32 weeks will complete 20 weeks of extended flexible dosing AT. We will address 3 specific aims: AIM 1: Compare the effects of flexible versus standard dosing on CRF response rate. AIM 2: Ascertain the effects on adherence, safety, and patient-reported outcomes. AIM 3: Evaluate the effects of extended AT in CRF non-responders. IMPACT: This study challenges the current dogma that all patients respond equally to a fixed AT dose and will be the first to evaluate flexible AT dosing in any cancer population. Receiving cancer treatment is not a qualifying condition for structured AT and, as such, AT is not currently considered a standard aspect of cancer management. We anticipate the proposed trial will directly address an unmet clinical need by identifying the AT regimen that maximizes CRF response rate and, if successful, findings from this investigation will help guide the AT regimen for translation to clinical care.