Crawford Jeffrey
Solid Tumor Therapeutics Program, Duke Cancer Institute, Durham, North Carolina, USA.
Curr Opin Clin Nutr Metab Care. 2016 May;19(3):199-204. doi: 10.1097/MCO.0000000000000274.
This article highlights recent developments in the area of cancer cachexia and therapeutic interventions.
Therapeutic interventions in cancer cachexia have been guided by clinical studies focused on the central role of muscle and the increased use of CT imaging to measure the impact of skeletal muscle loss on clinical outcomes. At the translational level, a number of different model systems have emphasized the importance of blockade of tumor-induced inflammation and its potential impact on reversing the cachexia phenotype, including FN14, a receptor in the TNF pathway, as well as the parathyroid hormone-related protein. Clinical studies continue to demonstrate the importance of nutrition and exercise as part of a multimodality approach. Although a number of promising agents are being evaluated, both enobosarm, a selected androgen receptor modulator, and anamorelin, a ghrelin agonist have completed phase III trials. Both agents have shown significant impact on reversal of skeletal muscle loss, but inconsistent effect on physical function improvement. Anamorelin also has a positive effect on appetite and weight gain.
Further analysis of these studies, along with regulatory guidance, will be critical in the further development of these and other promising agents in the clinical management of patients with cancer cachexia.
本文重点介绍癌症恶病质领域的最新进展以及治疗干预措施。
癌症恶病质的治疗干预措施以临床研究为指导,这些研究聚焦于肌肉的核心作用以及越来越多地使用CT成像来测量骨骼肌损失对临床结局的影响。在转化层面,许多不同的模型系统强调了阻断肿瘤诱导的炎症及其对逆转恶病质表型的潜在影响的重要性,包括TNF途径中的受体FN14以及甲状旁腺激素相关蛋白。临床研究继续证明营养和运动作为多模式方法一部分的重要性。尽管正在评估多种有前景的药物,但选择性雄激素受体调节剂恩杂鲁胺和胃饥饿素激动剂阿那莫林均已完成III期试验。这两种药物均对骨骼肌损失的逆转显示出显著影响,但对身体功能改善的效果不一致。阿那莫林对食欲和体重增加也有积极作用。
对这些研究的进一步分析以及监管指导,对于这些及其他有前景的药物在癌症恶病质患者临床管理中的进一步开发至关重要。