Resistance Training to Reduce Chemotoxicity in Colon Cancer

抵抗训练可减少结肠癌的化学毒性

• 批准号: 9504593
• 负责人: BETTE J CAAN
• 金额: $ 86.38万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-15 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9504593
• 关键词: Address; Adjuvant Chemotherapy; Adjuvant Therapy; Adverse effects; Behavior Therapy; Body Composition; Body Surface Area; Body Weight; Body mass index; Body measure procedure; Calibration; California; Cancer Patient; Colon Carcinoma; Conduct Clinical Trials; Dana-Farber Cancer Institute; Diagnosis; Dose; Dose-Limiting; Drug Kinetics; Dual-Energy X-Ray Absorptiometry; Effectiveness; Ensure; Equilibrium; Exercise; Exercise Physiology; Fatty acid glycerol esters; Fluorouracil; Gender; Guidelines; Height; Home environment; Institutes; Interleukin-6; Intervention; Lead; Length; Life; Malignant Neoplasms; Measures; Muscle; Newly Diagnosed; Outcome; Overdose; Participant; Patient risk; Patients; Randomized; Randomized Clinical Trials; Receptors, Tumor Necrosis Factor, Type II; Savings; Scanning; TNFRSF1A gene; Toxic effect; Toxicity due to chemotherapy; Waiting Lists; Weight; base; cancer epidemiology; chemotherapy; clinical care; colon cancer patients; drug clearance; gastrointestinal; group intervention; high risk; improved; individual patient; individualized medicine; inflammatory marker; muscle form; neurotoxicity; oncology; outcome forecast; oxaliplatin; patient subsets; potential biomarker; reduced muscle mass; response; sarcopenia; strength training

ABSTRACT The proportions of fat mass (FM) and muscle mass (MM) in the body may have important implications for calibration of chemotherapy in patients with colon cancer (CC). Chemotherapy dosing is currently based on body surface area (BSA), which is derived from information on height and weight. Body weight or Body Mass Index (BMI), especially among cancer patients, is not an accurate measure of FM or MM. Given this inability to predict FM or MM, dosing by BSA may lead to underdosing (which may impact cancer-specific and overall survival) or overdosing (leading to dose-limiting toxicity [DLT] defined as toxicity from chemotherapy that requires subsequent reductions in or discontinuation of life-saving treatment). Results have shown that those with low MM, or sarcopenia, have a higher risk of DLT than those with normal MM. DLT impacts dose intensity and may compromise efficacy of chemotherapy. We propose to examine the effects of a randomized clinical trial conducted during chemotherapy of home based resistance training (RT) versus a waitlist control on DLT. Participants will be 180 newly diagnosed Stage II and III CC patients from Kaiser Permanente of Northern California (KPNC), the Penn State Cancer Institute (PSCI), and the Dana Farber Cancer Institute (DFCI). The intervention will begin during the first 6 weeks of chemotherapy and continue through the completion of treatment. Specifically, we will examine between group differences for resistance training versus weight list control for dose intensity and grade 3 and 4 toxicities as well as changes in MM and changes in inflammatory markers. Since approximately 40-45% of newly diagnosed CC patients have sarcopenia at diagnosis, we will examine if the benefits of exercise are greater for those who have low MM compared to normal MM. We will also examine specific inflammatory markers (e.g. CRP, IL-6 and TNF-RII) as potential biomarkers of baseline MM, and determine how they change in response to RT. To determine effects of change of MM on chemotherapy-specific drug clearance, we will examine the impact of RT induced body composition changes on the pharmacokinetics (PK) of 5-FU and oxaliplatin. If RT helps to reduce DLT and MM and inflammatory markers can identify those patients most-likely to benefit from tailored exercise guidelines, then assessment of these parameters can be used to help target high risk patients. Given that DLT is a common problem and there are large numbers of newly diagnosed CC patients with undetected sarcopenia, many of whom may require dose reductions due to low MM, this study has the potential to have a large impact on clinical care and improve prognosis of colon cancer.

摘要 脂肪质量(FM)和肌肉质量(MM)在身体中的比例可能对 结肠癌患者化疗的校准。化疗剂量目前是基于 身体表面积(BSA)，这是从身高和体重信息得出的。体重或体重 指数(BMI)，尤其是在癌症患者中，不是FM或MM的准确衡量标准。 预测FM或MM，BSA的剂量可能导致剂量不足(这可能会影响癌症的特异性和整体 存活)或过量(导致剂量限制毒性[DLT]，定义为化疗毒性 要求随后减少或停止救生治疗)。结果表明，这些 患有低MM或骨质疏松症的患者发生DLT的风险比MMT正常的患者高。DLT影响剂量强度 并可能影响化疗的疗效。我们建议检验随机临床试验的效果。 在家庭耐药训练(RT)化疗期间进行的试验与DLT的等待名单对照。 参与者将是来自北方Kaiser Permanente的180名新诊断的II和III期CC患者 加州癌症研究所(KPNC)、宾夕法尼亚州立癌症研究所(PSCI)和达纳·法伯癌症研究所(DFCI)。这个 干预将在化疗的前6周开始，并持续到完成 治疗。具体地说，我们将检查阻力训练与举重表之间的组间差异 控制剂量强度和3级和4级毒性以及MM和炎症的变化 记号笔。由于大约40%-45%的新诊断的CC患者在确诊时有肌质疏松症，我们将 检查一下，与正常MM相比，低MM的人锻炼的益处是否更大。我们会 也要检查特定的炎症标志物(例如，CRP、IL-6和TNF-RII)作为潜在的基线生物标志物 并确定它们如何随RT的变化而变化。要确定MM的变化对 化疗特异性药物清除后，我们将考察RT对机体成分变化的影响 5-FU和奥沙利铂的药代动力学研究如果RT有助于减少DLT和MM以及炎症 标记物可以确定哪些患者最有可能受益于量身定制的运动指南，然后评估 这些参数可用于帮助针对高危患者。鉴于DLT是一个常见的问题，并且 大量新诊断的CC患者患有未检测到的石棺减少症，其中许多人可能需要 低MM导致的剂量减少，这项研究有可能对临床护理产生很大影响并改进 结肠癌的预后。