Safety, tolerability and pharmacokinetics of intravenous ghrelin for cancer-related anorexia/cachexia: a randomised, placebo-controlled, double-blind, double-crossover study.
Safety, tolerability and pharmacokinetics of intravenous ghrelin for cancer-related anorexia/cachexia: a randomised, placebo-controlled, double-blind, double-crossover study.
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DOI：
10.1038/sj.bjc.6604148
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发表时间：
2008-01-29
影响因子：
8.8
通讯作者：
Cerny, T.
中科院分区：
文献类型：
--
作者：
Strasser, F.;Lutz, T. A.;Maeder, M. T.;Thuerlimann, B.;Bueche, D.;Tschoep, M.;Kaufmann, K.;Holst, B.;Braendle, M.;von Moos, R.;Demmer, R.;Cerny, T.
21名成年患者随机在第1天和第8天接受Ghrelin治疗，在第4天和第11天接受安慰剂治疗，反之亦然，在午餐前60分钟内静脉注射：10例接受2 μg kg−1(低剂量)Ghrelin；11例接受8 μg kg−1(高剂量)Ghrelin。在基线(第1天前4-5天)、治疗期间和研究结束时(第17/18天)监测活动的和总的生长激素、生长激素(GH)和胰岛素样生长因子1水平。与药物相关的不良事件(通过NCI-CTC毒性标准和心脏检查进行评估)在Ghrelin和安慰剂之间没有区别。未观察到3/4级毒性或刺激肿瘤生长。GH是Ghrelin作用的生物标志物，小剂量GH升高峰值为25 ng m l−1，大剂量Ghrelin升高峰值为42 ng m l−1。研究结束时大剂量患者的早晨空腹总Ghrelin水平(3580 Pg ml−1)高于基线水平(990 Pg ml−1)。胰岛素样生长因子1水平没有变化。在第8天，81%的患者倾向于Ghrelin而不是安慰剂，而在研究结束时这一比例为63%。Ghrelin和安慰剂之间的营养摄入量和与饮食相关的症状，以探索初步疗效，没有区别。Ghrelin对晚期癌症患者耐受性良好且安全。在安全性、耐受性和患者的治疗偏好方面，低剂量组和高剂量组之间没有观察到差异。
Twenty-one adult patients were randomised to receive ghrelin on days 1 and 8 and placebo on days 4 and 11 or vice versa, given intravenously over a 60-min period before lunch: 10 received 2 μg kg−1 (lower-dose) ghrelin; 11 received 8 μg kg−1 (upper-dose) ghrelin. Active and total ghrelin, growth hormone (GH), and insulin-like growth factor 1 levels were monitored at baseline (4–5 days before day 1), during treatment days, and at end of study (day 17/18). Drug-related adverse events (assessed by NCI-CTC-toxicity criteria and cardiac examination) did not differ between ghrelin and placebo. No grade 3/4 toxicity or stimulation of tumour growth was observed. The peak increase of GH, a biological marker of ghrelin action, was 25 ng ml−1 with lower-dose and 42 ng ml−1 with upper-dose ghrelin. Morning fasting total ghrelin levels were higher (P<0.05) for upper-dose patients at end of study (3580 pg ml−1) than at baseline (990 pg ml−1). Insulin-like growth factor 1 levels did not change. At day 8, 81% of patients preferred ghrelin to placebo as against 63% at the end of study. Nutritional intake and eating-related symptoms, measured to explore preliminary efficacy, did not differ between ghrelin and placebo. Ghrelin is well tolerated and safe in patients with advanced cancer. For safety, tolerance, and patients' preference for treatment, no difference was observed between the lower- and upper-dose group.
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