Reduced Muscle Loss in Patients With NSCLC Taking Fibrates: Findings From a Retrospective Observational Study
ABSTRACT Background 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...
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| Format: | Article |
| Language: | English |
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Wiley
2025-08-01
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| Series: | Journal of Cachexia, Sarcopenia and Muscle |
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| Online Access: | https://doi.org/10.1002/jcsm.70016 |
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| author | Rahmi Elahjji Tahj Blow Rahul Grover Maurice A. Hurd Richard F. Dunne Bette J. Caan Elizabeth M. Cespedes Feliciano Andrew J. Plodkowski James H. Flory Marcus D. Goncalves |
| author_facet | Rahmi Elahjji Tahj Blow Rahul Grover Maurice A. Hurd Richard F. Dunne Bette J. Caan Elizabeth M. Cespedes Feliciano Andrew J. Plodkowski James H. Flory Marcus D. Goncalves |
| author_sort | Rahmi Elahjji |
| collection | DOAJ |
| description | ABSTRACT Background 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. Methods 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. Results 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. Conclusion 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. |
| format | Article |
| id | doaj-art-80e6022a036745e98f9768ab6ca7f3ae |
| institution | Kabale University |
| issn | 2190-5991 2190-6009 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
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| series | Journal of Cachexia, Sarcopenia and Muscle |
| spelling | doaj-art-80e6022a036745e98f9768ab6ca7f3ae2025-08-22T07:30:53ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092025-08-01164n/an/a10.1002/jcsm.70016Reduced Muscle Loss in Patients With NSCLC Taking Fibrates: Findings From a Retrospective Observational StudyRahmi Elahjji0Tahj Blow1Rahul Grover2Maurice A. Hurd3Richard F. Dunne4Bette J. Caan5Elizabeth M. Cespedes Feliciano6Andrew J. Plodkowski7James H. Flory8Marcus D. Goncalves9Weill Cornell Medicine New York New York USAWeill Cornell Medicine New York New York USAWeill Cornell Medicine New York New York USAWeill Cornell Medicine New York New York USAUniversity of Rochester Medical Center Rochester New York USAKaiser Permanente Oakland California USAKaiser Permanente Oakland California USAMemorial Sloan Kettering Cancer Center New York New York USAMemorial Sloan Kettering Cancer Center New York New York USAWeill Cornell Medicine New York New York USAABSTRACT Background 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. Methods 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. Results 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. Conclusion 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.https://doi.org/10.1002/jcsm.70016cachexiafibrateslung cancerPPAR‐αskeletal muscle |
| spellingShingle | Rahmi Elahjji Tahj Blow Rahul Grover Maurice A. Hurd Richard F. Dunne Bette J. Caan Elizabeth M. Cespedes Feliciano Andrew J. Plodkowski James H. Flory Marcus D. Goncalves Reduced Muscle Loss in Patients With NSCLC Taking Fibrates: Findings From a Retrospective Observational Study Journal of Cachexia, Sarcopenia and Muscle cachexia fibrates lung cancer PPAR‐α skeletal muscle |
| title | Reduced Muscle Loss in Patients With NSCLC Taking Fibrates: Findings From a Retrospective Observational Study |
| title_full | Reduced Muscle Loss in Patients With NSCLC Taking Fibrates: Findings From a Retrospective Observational Study |
| title_fullStr | Reduced Muscle Loss in Patients With NSCLC Taking Fibrates: Findings From a Retrospective Observational Study |
| title_full_unstemmed | Reduced Muscle Loss in Patients With NSCLC Taking Fibrates: Findings From a Retrospective Observational Study |
| title_short | Reduced Muscle Loss in Patients With NSCLC Taking Fibrates: Findings From a Retrospective Observational Study |
| title_sort | reduced muscle loss in patients with nsclc taking fibrates findings from a retrospective observational study |
| topic | cachexia fibrates lung cancer PPAR‐α skeletal muscle |
| url | https://doi.org/10.1002/jcsm.70016 |
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