Division of Endocrinology, Diabetes and Metabolism, Center for Translational Research on Inflammatory Diseases (CTRID), Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine , 2002 Holcombe Blvd, Building 109, Room 210, Houston, TX 77030 USA 713 794 7989 ; 713 794 7771 ;
Expert Opin Pharmacother. 2015 Jun;16(8):1245-53. doi: 10.1517/14656566.2015.1041500. Epub 2015 May 6.
Cancer anorexia-cachexia syndrome (CACS) is associated with increased morbidity and mortality. Anamorelin is a novel, orally active ghrelin receptor agonist in clinical development for the treatment of CACS in NSCLC. The aim of this review is to summarize preclinical and clinical studies evaluating anamorelin as a potential promising treatment for CACS in NSCLC.
Pharmacodynamics, pharmacokinetics and metabolism, clinical efficacy, safety and tolerability of anamorelin for the treatment of CACS in NSCLC were reviewed. Anamorelin administration may lead to increases in food intake, body weight and lean body mass, and a stimulatory effect on growth hormone secretion in NSCLC patients. Anamorelin is well tolerated with no dose-limiting toxicities identified to date.
Targeting ghrelin receptors presents the advantage of potentially addressing multiple mechanisms of CACS simultaneously including appetite, muscle protein balance, adipose tissue metabolism, energy expenditure and inflammation. Clinical data suggest that anamorelin is well tolerated and it effectively increases appetite, body weight and lean mass in patients with advanced NSCLC. Long-term safety remains unknown at this time. The potential synergistic effects of anamorelin with nutritional support or exercise as well as its efficacy/safety in other tumor types are also unknown.
癌症恶病质厌食症(CACS)与发病率和死亡率的增加有关。Anamorelin 是一种新型的、口服有效的 ghrelin 受体激动剂,目前正在临床开发中,用于治疗非小细胞肺癌(NSCLC)中的 CACS。本综述的目的是总结评估 anamorelin 作为 NSCLC 中 CACS 潜在有前途的治疗方法的临床前和临床研究。
评估 anamorelin 治疗 NSCLC 中 CACS 的药效学、药代动力学和代谢、临床疗效、安全性和耐受性。Anamorelin 的给药可能导致食物摄入、体重和瘦体重增加,并对 NSCLC 患者的生长激素分泌产生刺激作用。到目前为止,anamorelin 具有良好的耐受性,尚未确定剂量限制毒性。
靶向 ghrelin 受体具有潜在的优势,可以同时针对 CACS 的多种机制,包括食欲、肌肉蛋白平衡、脂肪组织代谢、能量消耗和炎症。临床数据表明,anamorelin 耐受性良好,能有效增加晚期 NSCLC 患者的食欲、体重和瘦体重。目前尚不清楚其长期安全性。anamorelin 与营养支持或运动的协同作用及其在其他肿瘤类型中的疗效/安全性也尚不清楚。