Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial
Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial
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DOI：
10.1016/s1470-2045(13)70549-7
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发表时间：
2014-01-01
期刊：
影响因子：
51.1
通讯作者：
Dunn, Janet A.
中科院分区：
文献类型：
--
作者：
Ford, Hugo E. R.;Marshall, Andrea;Dunn, Janet A.
背景：对于对铂类和氟嘧啶类药物无效的食管胃腺癌患者，二线化疗并未显示出对健康相关生活质量(HRQOL)的益处。我们评估了在主动症状控制中单独使用多西紫杉醇是否可以改善患者的存活率和HRQL。方法在这项开放标签的多中心试验中，我们从30个英国中心招募了18岁或以上的患者。如果患者有组织学证实的晚期食管腺癌、食管胃交界处或胃部，在接受铂-氟嘧啶联合治疗时或在治疗6个月内进展，则符合条件。患者的东部合作肿瘤组表现状态可能为0-2。我们随机分配使用中央计算机化最小化程序的患者接受多西紫杉醇加主动症状控制，或仅接受主动症状控制(1：1；根据疾病状态、疾病部位、对先前化疗的有效时间和表现状态进行分层)。多西紫杉醇75 mg/m(2)静脉滴注，每3周一次，共6个周期。主要终点是总体存活率，按治疗意向进行分析。这是计划最终分析的报告。这项研究是一项国际标准化随机对照试验，编号为ISRCTN13366390。在2008年4月21日至2012年4月26日期间，我们招募了168名患者，每个治疗组分配84名患者。经过12个月的中位随访[IQR 10-21]和161例(96%)死亡(多西紫杉醇组80例，活跃症状控制组81例)，多西紫杉醇组的中位总生存期为5.2个月(95%可信区间4.1~5.9)，而活跃症状对照组的中位总生存期为3.6个月(危险比0.67，95%可信区间0.49~0.92；p=0.01)。多西紫杉醇与3-4级中性粒细胞减少症(12例[15%]对无患者)、感染(15例[19%]对2例[3%])和发热性中性粒细胞减少症(6例[7%]对无患者)的发生率较高有关。接受多西紫杉醇治疗的患者疼痛减轻(p=0.0008)，恶心呕吐(p=0.02)和便秘(p=0.02)减少。两组的总体HRQOL相似(p=0.53)。疾病特异性的HRQOL测量也显示多西紫杉醇在减少吞咽困难(p=0.02)和腹痛(p=0.01)方面有好处。我们的研究结果表明，多西紫杉醇可以被推荐作为对铂和氟嘧啶治疗无效的食管胃腺癌患者的合适的二线治疗。
Background Second-line chemotherapy for patients with oesophagogastric adenocarcinoma refractory to platinum and fluoropyrimidines has not shown benefits in health-related quality of life (HRQoL). We assessed whether the addition of docetaxel to active symptom control alone can improve survival and HRQoL for patients.Methods For this open-labelled, multicentre trial, we recruited patients aged 18 years or older from 30 UK centres. Patients were eligible if they had an advanced, histologically confirmed adenocarcinoma of the oesophagus, oesophagogastric junction, or stomach that had progressed on or within 6 months of treatment with a platinum-fluoropyrimidine combination. Patients could have an Eastern Cooperative Oncology Group performance status of 0-2. We randomly assigned patients using a central, computerised minimisation procedure to receive docetaxel plus active symptom control, or active symptom control alone (1:1; stratified by disease status, disease site, duration of response to previous chemotherapy, and performance status). Docetaxel was given at a dose of 75 mg/m(2) by intravenous infusion every 3 weeks for up to six cycles. The primary endpoint was overall survival, analysed by intention to treat. This is the report of the planned final analysis. This study is an International Standardised Randomised Controlled Trial, number ISRCTN13366390.Findings Between April 21, 2008, and April 26, 2012, we recruited 168 patients, allocating 84 to each treatment group. After a median follow-up of 12 months [IQR 10-21]) and 161 (96%) deaths (80 in the docetaxel group, 81 in the active symptom control group), median overall survival in the docetaxel group was 5.2 months (95% CI 4.1-5.9) versus 3.6 months (3.3-4.4) in the active symptom control group (hazard ratio 0.67, 95% CI 0.49-0.92; p=0.01). Docetaxel was associated with higher incidence of grade 3-4 neutropenia (12 [15%] patients vs no patients), infection (15 [19%] patients vs two [3%] patients), and febrile neutropenia (six [7%] patients vs no patients). Patients receiving docetaxel reported less pain (p=0.0008) and less nausea and vomiting (p=0.02) and constipation (p=0.02). Global HRQoL was similar between the groups (p=0.53). Disease specific HRQoL measures also showed benefits for docetaxel in reducing dysphagia (p=0.02) and abdominal pain (p=0.01).Interpretation Our findings suggest that docetaxel can be recommended as an appropriate second-line treatment for patients with oesophagogastric adenocarcinoma that is refractory to treatment with platinum and fluoropyrimidine.