Department of Surgery, Surgical Metabolic Research Laboratory at Lundberg Laboratory for Cancer Research, Sahlgrenska Academy and University Hospital, Gothenburg, Sweden.
Cancer. 2010 Apr 15;116(8):2044-52. doi: 10.1002/cncr.24917.
The short-term provision of ghrelin to patients with cancer indicates that there may be benefits from long-term provision of ghrelin for the palliative treatment of weight-losing cancer patients. This hypothesis was evaluated in a randomized, double-blind, phase 2 study.
Weight-losing cancer patients with solid gastrointestinal tumors were randomized to receive either high-dose ghrelin treatment (13 microg/kg daily; n = 17 patients) or low-dose ghrelin treatment (0.7 microg/kg daily; n = 14 patients) for 8 weeks as a once-daily, subcutaneous injections. Appetite was scored on a visual analog scale; and food intake, resting energy expenditure, and body composition (dual x-ray absorpitometry) were measured before the start of treatment and during follow-up. Serum levels of ghrelin, insulin, insulin-like growth factor 1, growth hormone (GH), triglycerides, free fatty acids, and glucose were measured. Health-related quality of life, anxiety, and depression were assessed by using standardized methods (the 36-item Short Form Health Survey and the Hospital Anxiety and Depression Scale). Physical activity, rest, and sleep were measured by using a multisensor body monitor.
Treatment groups were comparable at inclusion. Appetite scores were increased significantly by high-dose ghrelin analyzed both on an intent-to-treat basis and according to the protocol. High-dose ghrelin reduced the loss of whole body fat (P < .04) and serum GH (P < .05). There was a trend for high-dose ghrelin to improve energy balance (P < .07; per protocol). Otherwise, no statistically significant differences in outcome variables were observed between the high-dose and low-dose groups. Adverse effects were not observed by high-dose ghrelin, such as serum levels of tumor markers (cancer antigen 125 [CA 125], carcinoembryonic antigen, and CA 19-9).
The current results suggested that daily, long-term provision of ghrelin to weight-losing cancer patients with solid tumors supports host metabolism, improves appetite, and attenuates catabolism.
短期给予癌症患者胃饥饿素表明，长期给予胃饥饿素可能有益于癌症消瘦患者的姑息治疗。这一假说在一项随机、双盲、2 期研究中得到了评估。
患有实体胃肠道肿瘤的消瘦癌症患者被随机分为高剂量胃饥饿素治疗组（13μg/kg 每日；n=17 例）或低剂量胃饥饿素治疗组（0.7μg/kg 每日；n=14 例），作为每日一次的皮下注射，持续 8 周。通过视觉模拟评分法评估食欲；在治疗前和随访期间测量食物摄入量、静息能量消耗和身体成分（双能 X 线吸收法）。测量血清胃饥饿素、胰岛素、胰岛素样生长因子 1、生长激素（GH）、甘油三酯、游离脂肪酸和葡萄糖水平。采用标准化方法（36 项简短健康调查和医院焦虑抑郁量表）评估健康相关生活质量、焦虑和抑郁。通过多传感器身体监测器测量身体活动、休息和睡眠。
纳入时治疗组具有可比性。高剂量胃饥饿素治疗后，基于意向治疗和方案分析，食欲评分均显著增加。高剂量胃饥饿素减少了全身脂肪的丢失（P<.04）和血清 GH（P<.05）。高剂量胃饥饿素改善能量平衡的趋势有统计学意义（P<.07；按方案）。否则，高剂量和低剂量组之间在结局变量上没有观察到统计学上的显著差异。高剂量胃饥饿素未观察到不良反应，如肿瘤标志物（CA125、癌胚抗原和 CA19-9）的血清水平。
目前的结果表明，每天长期给予消瘦的实体瘤癌症患者胃饥饿素可支持宿主代谢，改善食欲，减轻分解代谢。
