da Fonseca Guilherme Wesley Peixoto, Sato Ryosuke, de Nazaré Nunes Alves Maria Janieire, von Haehling Stephan
Department of Cardiovascular Rehabilitation and Exercise Physiology, Heart Institute (Incor), University of São Paulo Medical School, São Paulo, Brazil.
Academic Research Organization of the Heart Institute (ARO-InCor), São Paulo, Brazil.
Expert Opin Pharmacother. 2023 Apr;24(5):629-639. doi: 10.1080/14656566.2023.2194489. Epub 2023 Mar 30.
Cancer cachexia is a multifactorial metabolic syndrome associated with a pathophysiology intertwined with increased inflammatory response, anorexia, metabolic dysregulation, insulin resistance, and hormonal alterations, which together generate a negative energy balance in favor of catabolism. The development of therapeutic strategies to treat cancer cachexia has always been related to clinical interventions with increased food intake/supplementation, physical exercise regimens, and/or medication to attenuate catabolism and increase the anabolic response. However, the approval of drugs by regulatory agencies has always been a challenge.
This review outlines the main pharmacotherapy findings in cancer cachexia as well as the ongoing clinical trials that have evaluated changes in body composition and muscle function. The National Library of Medicine (PubMed) was used as search tool.
The pharmacological therapy for cachexia should be focused on improving body composition, muscle function, and mortality, although none of the compounds used so far was able to demonstrate positive results beyond increased appetite and improvements in body composition. Ponsegromab (GDF15 inhibitor), a new compound that has just entered a phase II clinical trial, is a promising candidate to treat cancer cachexia and may produce exciting results if the study can be conducted as planned.
癌症恶病质是一种多因素代谢综合征,其病理生理学与炎症反应增加、厌食、代谢失调、胰岛素抵抗和激素改变相互交织,共同导致有利于分解代谢的负能量平衡。治疗癌症恶病质的治疗策略的发展一直与增加食物摄入/补充、体育锻炼方案和/或药物治疗以减轻分解代谢并增加合成代谢反应的临床干预措施相关。然而,监管机构对药物的批准一直是一个挑战。
本综述概述了癌症恶病质的主要药物治疗研究结果以及评估身体成分和肌肉功能变化的正在进行的临床试验。美国国立医学图书馆(PubMed)用作搜索工具。
恶病质的药物治疗应侧重于改善身体成分、肌肉功能和死亡率,尽管迄今为止使用的化合物均未显示出除增加食欲和改善身体成分之外的积极结果。刚进入II期临床试验的新化合物ponsegromab(GDF15抑制剂)是治疗癌症恶病质的有希望的候选药物,如果研究能够按计划进行,可能会产生令人兴奋的结果。