Anamorelin for patients with cancer cachexia: an integrated analysis of two phase 2, randomised, placebo-controlled, double-blind trials
Anamorelin for patients with cancer cachexia: an integrated analysis of two phase 2, randomised, placebo-controlled, double-blind trials
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DOI：
10.1016/s1470-2045(14)71154-4
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发表时间：
2015-01-01
期刊：
影响因子：
51.1
通讯作者：
Friend, John
中科院分区：
文献类型：
--
作者：
Garcia, Jose M.;Boccia, Ralph V.;Friend, John
癌症恶病质综合征与发病率和死亡率的增加有关。阿拉莫林是一种口服生长激素释放肽受体激动剂，具有增强食欲和合成代谢活性。我们评估的影响anamorelin对身体成分，强度，生活质量，生化标志物，和安全性的患者与癌症madoxia-cachexia.Methods数据汇总，先验，从两个完成的2期，多中心，安慰剂对照，双盲试验中晚期或无法治愈的癌症和体重减轻5%或以上的患者。患者按体重减轻严重程度（5- 15%，>15%）分层，并按计算机生成的随机化时间表随机分配（1：1）至盐酸阿拉莫林50 mg或安慰剂组，每日一次，持续12周。主要结局是在12周治疗期间通过双能X线吸收测定法测定至少接受过一剂研究药物的合格患者的瘦体重和治疗后疗效评估。我们评估了所有接受至少一剂研究药物的患者的安全性。这些试验在ClinicalTrials.gov注册，编号为NCT 00219817和NCT 00267358。结果在2005年6月29日至2006年10月26日期间，我们招募了44名阿拉莫林组患者和38名安慰剂组患者。74例患者有资格进行疗效分析。在12周内，阿拉莫林组38名患者的瘦体重增加了1.89 kg的最小二乘均值（95% CI 0.84 - 2.95），而最小二乘均值降低-0.20 kg（-1.23至0.83）（差异2.09 kg [0.94-3.25]; p=0.0006）。44例接受阿拉莫林治疗的患者中有42例（95%）和38例接受安慰剂治疗的患者中有33例（87%）出现不良事件。最常见的3-4级不良事件阿拉莫林组的不良反应（治疗相关或不相关）为疲乏、无力、房颤和呼吸困难（各两个[5%]）;在安慰剂组，这些事件是肺炎（3例[8%]）和贫血、血小板减少、腹痛、焦虑，和呼吸困难（各2例[5%]）。解释阿拉莫林治疗12周在癌症恶病质综合征患者中具有有利的临床反应特征。这些发现支持在这种情况下进一步调查。
Background Cancer anorexia-cachexia syndrome is associated with increased morbidity and mortality. Anamorelin is an oral ghrelin-receptor agonist with appetite-enhancing and anabolic activity. We assessed the effects of anamorelin on body composition, strength, quality of life, biochemical markers, and safety in patients with cancer anorexia-cachexia.Methods Data were pooled, a priori, from two completed phase 2, multicentre, placebo-controlled, double-blind trials in patients with advanced or incurable cancer and weight loss of 5% or more. Patients were stratified by weight loss severity (5-15%, >15%) and randomly allocated (1: 1) with a computer-generated randomisation schedule to anamorelin hydrochloride 50 mg or placebo once-daily for 12 weeks. Primary outcome was lean body mass by dual-energy x-ray absorptiometry over the 12 week treatment period in eligible patients who had at least one dose of study drug and post-treatment efficacy assessment. We assessed safety in all patients who received at least one dose of study drug. The trials are registered with ClinicalTrials.gov, numbers NCT00219817 and NCT00267358.Findings Between June 29, 2005, and Oct 26, 2006, we enrolled 44 patients in the anamorelin group and 38 patients in the placebo group. 74 patients were eligible for the efficacy analyses. Over 12 weeks, lean body mass increased in 38 patients in the anamorelin group by a least-squares mean of 1.89 kg (95% CI 0.84 to 2.95) compared with a decrease of a least-squares mean of -0.20 kg (-1.23 to 0.83) for 36 patients in the placebo group (difference 2.09 kg [0.94-3.25]; p=0.0006). 42 (95%) of 44 patients treated with anamorelin and 33 (87%) of 38 patients treated with placebo had adverse events. The most common grade 3-4 adverse events (treatment-related or not) in the anamorelin group were fatigue, asthenia, atrial fibrillation, and dyspnoea (two [5%] each); in the placebo group, such events were pneumonia (three [8%]) and anaemia, thrombocytopenia, abdominal pain, anxiety, and dyspnoea (two [5%] each).Interpretation Anamorelin treatment for 12 weeks had a favourable clinical response profile in patients with cancer anorexia-cachexia syndrome. These findings support further investigation in this setting.