天然ghrelin,一种多肽生长激素促分泌素,对恶病质有治疗潜力.我们设计了皮下天然生长素释放肽的剂量发现试验,以改善晚期癌症患者的营养摄入(NI)。
晚期癌症患者恶病质管理(症状管理,物理治疗,营养,和社会心理支持)始于32μg/kg体重的生长素释放肽,其次是50%的剂量增加。患者每天两次自我注射ghrelin,持续4天,然后进行冲洗期。到达主要终点后,最大NI(最大NI的最小剂量),随后是维持期,患者每周注射10剂生长素释放肽.安全参数,NI,和恶病质结果(症状,叙事,肌肉质量,和强度)在6周内进行测量。
包括10例转移性实体瘤患者,和六个(100%男性,平均年龄61.8±8.5SD)接受生长素释放肽。四名患者达到了最大NI的最小剂量。3例患者达到研究结束访视。Ghrelin在食欲和饮食相关症状方面具有不同的结果,但在叙述中具有积极作用。与基线相比,最终测量时的食欲和恶病质治疗平均功能评估评分低6.8分,t(5)=5.98,P<.01。两名患者肌肉质量稳定,一名患者肌肉质量增加,三名患者的肌肉力量稳定。主观耐受性高。患者表现出波动的轨迹,中位生存期为88天(51-412天)。
Ghrelin在晚期癌性恶病质患者中是安全的,无剂量限制性毒性且耐受性良好。干预非常复杂,纳入的患者数量很少。对营养摄入和患者叙述有积极影响。
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.