多西他赛对比积极症状控制治疗难治性胃食管腺癌（COUGAR-02）：一项开放标签、3 期随机对照试验。

Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial.

机构信息

Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.

Warwick Clinical Trials Unit, Coventry, UK.

出版信息

Lancet Oncol. 2014 Jan;15(1):78-86. doi: 10.1016/S1470-2045(13)70549-7. Epub 2013 Dec 10.

DOI:10.1016/S1470-2045(13)70549-7

PMID:24332238

Abstract

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.

FUNDING

Cancer Research UK.

摘要

背景

对于对铂类和氟嘧啶类药物耐药的食管胃腺癌患者，二线化疗并未显示在健康相关生活质量（HRQoL）方面获益。我们评估了多西他赛联合积极症状控制是否可以改善患者的生存和 HRQoL。

方法

在这项开放标签、多中心试验中，我们从英国的 30 个中心招募了年龄在 18 岁及以上的患者。符合条件的患者为患有晚期、组织学证实的食管、食管胃交界处或胃腺癌，在铂类氟嘧啶联合治疗后或治疗后 6 个月内进展。患者的东部合作肿瘤学组表现状态可为 0-2。我们使用中央计算机化最小化程序对患者进行随机分组，以接受多西他赛联合积极症状控制或单独积极症状控制（1:1；按疾病状态、疾病部位、对先前化疗的反应持续时间和表现状态分层）。多西他赛的剂量为 75mg/m2，静脉输注，每 3 周一次，最多 6 个周期。主要终点为总体生存，通过意向治疗进行分析。这是计划的最终分析报告。这项研究是一个国际标准化随机对照试验，编号为 ISRCTN13366390。

结果

2008 年 4 月 21 日至 2012 年 4 月 26 日，我们招募了 168 名患者，将 84 名患者分配到每个治疗组。中位随访 12 个月[IQR 10-21]后，有 161 名（96%）患者死亡（多西他赛组 80 名，积极症状控制组 81 名）。多西他赛组的中位总生存期为 5.2 个月（95%CI 4.1-5.9），而积极症状控制组为 3.6 个月（3.3-4.4）（风险比 0.67，95%CI 0.49-0.92；p=0.01）。多西他赛组更常发生 3-4 级中性粒细胞减少症（12 例[15%]患者 vs 无患者）、感染（15 例[19%]患者 vs 2 例[3%]患者）和发热性中性粒细胞减少症（6 例[7%]患者 vs 无患者）。接受多西他赛治疗的患者报告疼痛减轻（p=0.0008）、恶心和呕吐减轻（p=0.02）和便秘减轻（p=0.02）。两组之间的全球 HRQoL 相似（p=0.53）。疾病特异性 HRQoL 测量也表明多西他赛在减轻吞咽困难（p=0.02）和腹痛（p=0.01）方面具有优势。