A placebo-controlled double blind trial of etanercept for the cancer anorexia/weight loss syndrome - Results from NOOC1 from the North Central Cancer Treatment Group
A placebo-controlled double blind trial of etanercept for the cancer anorexia/weight loss syndrome - Results from NOOC1 from the North Central Cancer Treatment Group
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DOI：
10.1002/cncr.22944
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发表时间：
2007-09-15
期刊：
影响因子：
6.2
通讯作者：
Loprinzi, Charles L.
中科院分区：
文献类型：
--
作者：
Jatoi, Aminah;Dakhil, Shaker R.;Loprinzi, Charles L.
背景肿瘤坏死因子-α（TNF-α）是癌症厌食/体重减轻综合征的假定介质。目前的研究旨在确定依那西普（一种二聚体融合蛋白，由人75千道尔顿TNF受体的胞外配体结合部分与人免疫球蛋白[1g] G1的Fc部分连接组成）是否可以减轻这种综合征。共有63例可评价患者被随机分配接受依那西普25 mg皮下注射，每周两次，对比安慰剂。所有患者均患有无法治愈的恶性肿瘤，承认体重和/或食欲下降是一个问题，并报告在2个月内体重减轻> 2.27 kg和/或每日摄入量< 20卡路里/kg体重。随着时间的推移，发现两个治疗组的体重增加都很小;没有患者体重增加>=基线体重的10%。先前验证的食欲问卷显示，两个治疗组的改善可忽略不计。中位生存期也相当（依那西普治疗和安慰剂暴露患者分别为175天和148天; P = 0.82）。最后，关于不良事件的初步数据表明，接受依那西普治疗的患者神经毒性发生率较高（29% vs 0%），但贫血（0% vs 19%）和血小板减少症（0% vs 14%）的发生率较低。两组的感染率都可以忽略不计。TNF-alpha-238和TNF-alpha-308多态性的基因分型显示这些基因型没有临床意义，除了-238 G/A基因型的存在与相对较差的生存率之间的初步关联。依那西普，在目前的试验中规定，似乎没有减轻癌症厌食症/体重减轻综合征的晚期疾病患者。
BACKGROUND. Tumor necrosis factor-a (TNF-alpha) is a putative mediator of the cancer anorexia/weight loss syndrome. The current study was designed to determine whether etanercept (a dimeric fusion protein consisting of the extracellular ligand-binding portion of the human 75-kilodalton TNF receptor linked to the Fc portion of human immunoglobulin [1g] G1) could palliate this syndrome.METHODS. A total of 63 evaluable patients were randomly assigned to receive either etanercept at a dose of 25 mg subcutaneously twice weekly versus a cornparably administered placebo. All patients had an incurable malignancy, acknowledged loss of weight and/or appetite as a concern, and reported a weight loss of > 2.27 kg over 2 months and/or a daily intake of < 20 calories/kg body weight.RESULTS. Over time, weight gain was found to be minimal in both treatment arms; no patient gained >= 10% of their baseline weight. Previously validated appetite questionnaires revealed negligible improvements in both treatment arms. The median survival was also comparable (175 days vs 148 days in etanercept-treated and placebo-exposed patients, respectively; P =.82). Finally, preliminary data regarding adverse events demonstrated that patients treated with etanercept had higher rates of neurotoxicity (29% vs 0%) but lower rates of anemia (0% vs 19%) and thrombocytopenia (0% vs 14%). Infection rates were negligible in both groups. Genotyping for TNF-alpha-238 and TNF-alpha-308 polymorphisms revealed no clinical significance for these genotypes, except for a preliminary association between presence of the -238 G/A genotype and relatively less favorable survival.CONCLUSIONS. Etanercept, as prescribed in the current trial, does not appear to palliate the cancer anorexia/weight loss syndrome in patients with advanced disease.