A randomized phase III clinical trial of a combined treatment for cachexia in patients with gynecological cancers: Evaluating the impact on metabolic and inflammatory profiles and quality of life
A randomized phase III clinical trial of a combined treatment for cachexia in patients with gynecological cancers: Evaluating the impact on metabolic and inflammatory profiles and quality of life
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DOI：
10.1016/j.ygyno.2011.12.435
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发表时间：
2012-03-01
影响因子：
4.7
通讯作者：
Mantovani, Giovanni
中科院分区：
文献类型：
--
作者：
Maccio, Antonio;Madeddu, Clelia;Mantovani, Giovanni
目标.妇科肿瘤疾病进展的特征在于特定的能量代谢改变和包括疲劳、厌食、恶心、贫血和免疫抑制的症状，其导致恶病质综合征和患者生活质量（QoL）的显著降低。治疗方案与适当和有效的心理和社会支持系统是必不可少的，以抵消症状的肿瘤性疾病在不可治愈的患者。进行了一项III期随机研究，以确定改善晚期妇科癌症患者关键症状的最有效和最安全的治疗方法，即，瘦体重（LBM）、静息能量消耗（REE）、疲劳和生活质量。此外，还评价了治疗组对主要代谢和炎症参数的影响，包括C-反应蛋白（CRP）、白细胞介素（IL）-6、肿瘤坏死因子（TNF）-α、瘦素、活性氧（ROS）和谷胱甘肽过氧化物酶。还评估了治疗期间格拉斯哥预后评分（GPS）的变化。共有104名晚期妇科癌症患者入选，并随机分配接受醋酸甲地孕酮（MA）加左旋卡尼汀、塞来昔布和抗氧化剂（第1组）或单用MA（第2组）。疗程4个月。在LBM、REE、疲劳和总体QoL方面，联合治疗组比第2组更有效。至于次要疗效终点，两组患者食欲增加，ECOG PS显著降低。炎症和氧化应激参数IL-6、TNIF-alpha、CRP和ROS在第1组中显著降低，而在第2组中未观察到显著变化。联合治疗改善了免疫代谢改变和患者QoL。恶病质的多模式治疗理想地应该在“最佳支持性护理”的背景下引入，包括最佳的症状管理和仔细的心理咨询。(C)2011 Elsevier Inc. All rights reserved.
Objectives. Gynecological neoplastic disease progression is characterized by specific energy metabolism alterations and by symptoms including fatigue, anorexia, nausea, anemia, and immunodepression, which result in a cachexia syndrome and a marked decrease in patient quality of life (QoL). Therapeutic protocols associated with appropriate and effective psychological and social support systems are essential to counteract the symptoms of neoplastic disease in incurable patients.Methods. A phase III randomized study was performed to establish the most effective and safest treatment to improve the key symptoms in advanced gynecological cancer patients, i.e., lean body mass (LBM), resting energy expenditure (REE), fatigue, and QoL. In addition, the impact of the treatment arms on the main metabolic and inflammatory parameters, including C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, leptin, reactive oxygen species (ROS), and glutathione peroxidase, was evaluated. The change in the Glasgow Prognostic Score (GPS) during treatment was also assessed. A total of 104 advanced-stage gynecological cancer patients were enrolled and randomly assigned to receive either megestrol acetate (MA) plus L-carnitine, celecoxib, and antioxidants (arm 1) or MA alone (arm 2). The treatment duration was 4 months.Results. The combination arm was more effective than arm 2 with respect to LBM, REE, fatigue, and global QoL. As for the secondary efficacy endpoints, patient appetite increased, and ECOG PS decreased significantly in both arms. The inflammation and oxidative stress parameters IL-6, TNIF-alpha, CRP, and ROS decreased significantly in arm 1, while no significant change was observed in arm 2.Conclusions. The combined treatment improved both immunometabolic alterations and patient QoL. Multimodality therapies for cachexia ideally should he introduced within a context of "best supportive care" that includes optimal symptom management and careful psychosocial counseling. (C) 2011 Elsevier Inc. All rights reserved.