Elahjji Rahmi, Blow Tahj, Grover Rahul, Hurd Maurice A, Dunne Richard F, Caan Bette J, Cespedes Feliciano Elizabeth M, Plodkowski Andrew J, Flory James H, Goncalves Marcus D
Weill Cornell Medicine, New York, New York, USA.
University of Rochester Medical Center, Rochester, New York, USA.
J Cachexia Sarcopenia Muscle. 2025 Aug;16(4):e70016. doi: 10.1002/jcsm.70016.
The cancer-anorexia-cachexia syndrome (CACS) is a common and debilitating wasting disorder characterized by loss of skeletal muscle and worse morbidity and mortality. In pre-clinical studies, CACS is associated with loss of peroxisome proliferator-activated receptor alpha (PPAR-α) dependent ketone production in the liver. Fibrates are PPAR-α agonists that are commonly used to treat dyslipidemia. Treating mice with fibrates was found to prevent skeletal muscle loss. We examine whether patients with cancer treated with PPAR-α agonists experience less CACS.
We performed a retrospective cohort study of patients (N = 6922) at Memorial Sloan Kettering Cancer Center who were diagnosed with non-small cell lung cancer (NSCLC) between 2002 and 2017 and were incidentally prescribed fenofibrate or gemfibrozil at the time of diagnosis. These patients were compared to a propensity score-matched control set who were not taking either drug. The primary outcome included a composite outcome of CACS, which included significant weight loss before or after the time of diagnosis. Secondary outcomes included change in cross-sectional skeletal muscle area over time as measured in serial CT imaging studies and overall survival. Descriptive statistics, Kaplan-Meier analysis and multivariable logistic regression were performed to compare outcomes between the two groups.
Among patients with NSCLC, 149 were taking fenofibrate or gemfibrozil at the time of diagnosis. A 2:1 propensity score-matched cohort of 298 patients was created that was well-matched with regard to baseline characteristics. Regarding the primary composite outcome, there was no significant difference in the prevalence of CACS between those taking fibrates and propensity-matched controls (49.7 vs. 46.6%). When skeletal muscle mass was measured directly using cross-sectional imaging, patients on fibrates were found to have lost significantly less muscle area over time (-3.3 vs.-4.2%, p = 0.03). There was no difference in overall survival between groups.
Patients with NSCLC taking fibrates at the time of diagnosis lost less muscle area over time. In a secondary analysis, this change was not associated with a change in overall survival, though this study was likely underpowered for this analysis.
癌症恶病质综合征（CACS）是一种常见且使人衰弱的消耗性疾病，其特征为骨骼肌流失以及更高的发病率和死亡率。在临床前研究中，CACS与肝脏中过氧化物酶体增殖物激活受体α（PPAR-α）依赖性酮生成的丧失有关。贝特类药物是常用的治疗血脂异常的PPAR-α激动剂。研究发现，用贝特类药物治疗小鼠可防止骨骼肌流失。我们研究了接受PPAR-α激动剂治疗的癌症患者是否较少发生CACS。
我们对纪念斯隆凯特琳癌症中心的患者（N = 6922）进行了一项回顾性队列研究，这些患者在2002年至2017年间被诊断为非小细胞肺癌（NSCLC），并在诊断时偶然开具了非诺贝特或吉非贝齐。将这些患者与未服用任何一种药物的倾向评分匹配对照组进行比较。主要结局包括CACS的复合结局，其中包括诊断前后的显著体重减轻。次要结局包括在系列CT成像研究中测量的随时间变化的横截面骨骼肌面积变化以及总生存期。进行描述性统计、Kaplan-Meier分析和多变量逻辑回归以比较两组之间的结局。
在NSCLC患者中，149例在诊断时服用非诺贝特或吉非贝齐。创建了一个2:1倾向评分匹配的298例患者队列，该队列在基线特征方面匹配良好。关于主要复合结局，服用贝特类药物的患者与倾向匹配对照组之间CACS的患病率无显著差异（49.7%对46.6%）。当使用横截面成像直接测量骨骼肌质量时，发现服用贝特类药物的患者随时间流失的肌肉面积明显更少（-3.3%对-4.2%，p = 0.03）。两组之间的总生存期无差异。
诊断时服用贝特类药物的NSCLC患者随时间流失的肌肉面积较少。在一项次要分析中，这种变化与总生存期的变化无关，尽管该研究可能对此分析的效力不足。
