Competence Center Palliative Care, Department of Radiation Oncology, Universitätsspital Zürich, Zürich, Switzerland.
School of Health Professions, Institute of Nursing, Zurich University of Applied Sciences, Winterthur, Switzerland.
J Cachexia Sarcopenia Muscle. 2021 Apr;12(2):506-516. doi: 10.1002/jcsm.12659. Epub 2021 Jan 15.
Natural ghrelin, a peptide growth hormone secretagogue, has a therapeutic potential in cachexia. We designed a dose-finding trial of subcutaneous natural ghrelin to improve nutritional intake (NI) in advanced cancer patients.
Advanced cancer patients with cachexia management (symptom management, physiotherapy, nutritional, and psychosocial support) started with ghrelin at 32 μg/kg body weight, followed by 50% dose increases. Patients self-injected ghrelin twice daily for 4 days followed by a wash-out period. After reaching the primary endpoint, maximal NI (minimal dose for maximal NI), a maintenance period followed during which patients injected 10 doses of ghrelin per week. Safety parameters, NI, and cachexia outcomes (symptoms, narratives, muscle mass, and strength) were measured over 6 weeks.
Ten patients with metastatic solid tumours were included, and six (100% male, mean age 61.8 ± 8.5 SD) received ghrelin. Minimal dose for maximal NI was reached in four patients. Three patients reached the end-of study visit. Ghrelin was well tolerated with variable results on appetite and eating-related symptoms but a positive effect in the narratives. Mean Functional Assessment of Appetite & Cachexia Therapy score was 6.8 points lower at final measurement compared with baseline, t(5) = 5.98, P < .01. Muscle mass was stable in two patients and increased in one patient, and muscle strength was stable in three patients. Subjective tolerability was high. Patients showed a fluctuating trajectory, and median survival was 88 days (51-412 days).
Ghrelin was safe in advanced patients with cancer cachexia without dose-limiting toxicity and well tolerated. The intervention was very complex, and the number of patients included was small. There was a positive effect on nutritional intake and patient narratives.
天然生长激素释放肽，一种肽类生长激素促分泌素，在恶病质治疗中有一定的应用潜力。我们设计了一项皮下给予天然生长激素释放肽的剂量探索试验，旨在改善晚期癌症患者的营养摄入（NI）。
接受恶病质管理（症状管理、物理治疗、营养和心理社会支持）的晚期癌症患者首先给予 32μg/kg 体重的生长激素释放肽，然后增加 50%的剂量。患者自行每天皮下注射生长激素释放肽两次，持续 4 天，然后停药。达到主要终点（达到最大 NI 的最小剂量）后，进入维持期，在此期间，患者每周注射 10 次生长激素释放肽。在 6 周内，通过安全性参数、NI 和恶病质结局（症状、叙述、肌肉量和力量）来评估。
10 名转移性实体瘤患者纳入研究，其中 6 名（100%为男性，平均年龄 61.8±8.5 岁）接受了生长激素释放肽治疗。4 名患者达到了最大 NI 的最小剂量。3 名患者完成了研究访视。生长激素释放肽耐受性良好，食欲和与进食相关的症状有所改善，但叙述中有积极的影响。最终测量时，功能性食欲评估和恶病质治疗评分平均降低 6.8 分，t(5)=5.98，P<0.01。2 名患者的肌肉量稳定，1 名患者的肌肉量增加，3 名患者的肌肉力量稳定。患者主观耐受良好。患者表现出波动的轨迹，中位生存时间为 88 天（51-412 天）。
生长激素释放肽在晚期癌症恶病质患者中是安全的，没有剂量限制毒性，且耐受性良好。该干预措施非常复杂，纳入的患者数量较少。它对营养摄入和患者叙述有积极影响。
