Velindre Cancer Centre, Velindre Hospital, Cardiff, UK.
Lancet Oncol. 2013 Jun;14(7):627-37. doi: 10.1016/S1470-2045(13)70136-0. Epub 2013 Apr 25.
Definitive chemoradiotherapy (CRT) is an alternative to surgery for the curative treatment of oesophageal carcinoma. The SCOPE1 trial aimed to investigate the addition of cetuximab to cisplatin and fluoropyrimidine-based definitive CRT in patients with localised oesophageal squamous-cell cancer and adenocarcinomas to assess activity, safety, and feasibility of use.
In this multicentre, randomised, open-label, phase 2/3 trial, we recruited patients aged 18 years and older from UK radiotherapy centres who had non-metastatic, histologically confirmed carcinoma of the oesophagus (adenocarcinoma, squamous-cell, or undifferentiated; WHO status 0-1; stage I-III disease) and been selected to receive definitive CRT. Patients were randomly assigned (1:1) via a central computerised system using stratified minimisation (with an 80:20 random element) to receive CRT alone or CRT with cetuximab (400 mg/m(2) on day 1 followed by 250 mg/m(2) weekly), stratified by recruiting hospital, primary reason for not having surgery, tumour histology, and tumour stage. CRT consisted of cisplatin 60 mg/m(2) (day 1) and capecitabine 625 mg/m(2) twice daily (days 1-21) for four cycles; cycles three and four were given concurrently with 50 Gy in 25 fractions of radiotherapy. The primary endpoint was the proportion of patients who were treatment failure free at week 24 for the phase 2 trial and overall survival for the phase 3 trial, both measured from randomisation. We analysed data by intention to treat. This trial is an International Standard Randomised Controlled Trial, number 47718479.
258 patients (129 assigned to each treatment group) from 36 UK centres were recruited between Feb 7, 2008, and Feb 22, 2012. Recruitment was stopped without continuation to phase 3 because the trial met criteria for futility, but we continued to follow-up recruited patients until all had reached at least 24-week follow-up (median follow-up of patients who survived was 16.8 months [IQR 11.2-24.5]). Fewer patients were treatment failure free at 24 weeks in the CRT plus cetuximab group (79 of 119 patients [66·4%, 90% CI 58·6-73·6]) than in the CRT only group (93 of 121 patients [76.9%, 69.7-83.0]). The CRT plus cetuximab group also had shorter median overall survival (22.1 months [95% CI 15.1-24.5] vs 25.4 months [20.5-37.9]; adjusted HR 1.53 [95% CI 1.03-2.27]; p=0.035). Patients who received CRT plus cetuximab had more non-haematological grade 3 or 4 toxicities (102 [79%] of 129 patients vs 81 [63%] of 129 patients; p=0.004). The most common grade 3 or 4 toxicities were low white blood cell count (14 [11%] in the CRT plus cetuximab group vs 21 [16%] in the CRT only group), low absolute neutrophil count (15 [12%] vs 24 [19%]), fatigue (26 [20%] vs 25 [19%]), and dysphagia (35 [27%] vs 37 [29%]).
The addition of cetuximab to standard chemotherapy and radiotherapy cannot be recommended for patients with oesophageal cancer suitable for definitive CRT.
Cancer Research UK.
确定性放化疗（CRT）是局部食管鳞状细胞癌和腺癌可切除治疗的替代方法。SCOPE1 试验旨在研究在局部食管鳞状细胞癌和腺癌患者中加入西妥昔单抗顺铂和氟嘧啶类的确定性 CRT，以评估其活性、安全性和可行性。
在这项多中心、随机、开放标签、2/3 期试验中，我们从英国放射治疗中心招募了年龄在 18 岁及以上的非转移性、组织学证实的食管癌（腺癌、鳞状细胞癌或未分化癌；世界卫生组织 0-1 级；I-III 期疾病）患者，并选择接受确定性 CRT。患者通过中央计算机系统以分层最小化（80:20 随机元素）随机分配（1:1）接受 CRT 单独治疗或 CRT 加西妥昔单抗（第 1 天 400mg/m²，随后每周 250mg/m²），分层依据招募医院、未手术的主要原因、肿瘤组织学和肿瘤分期。CRT 包括顺铂 60mg/m²（第 1 天）和卡培他滨 625mg/m² 每日 2 次（第 1-21 天），共 4 个周期；第 3 和第 4 个周期与放疗 50Gy 同时进行，共 25 次。主要终点是第 24 周无治疗失败的患者比例，第 3 期的主要终点是总生存率，均从随机分组开始测量。我们按意向治疗进行数据分析。该试验是国际标准随机对照试验，编号为 47718479。
2008 年 2 月 7 日至 2012 年 2 月 22 日，从 36 家英国中心招募了 258 名患者（每组 129 名）。由于试验达到了无效标准，招募被停止而没有继续进行第 3 期，但我们继续对招募的患者进行随访，直到所有患者都至少完成了 24 周的随访（中位随访时间为存活患者的 16.8 个月[IQR 11.2-24.5]）。与 CRT 组（79/119 例患者[66.4%，90%CI 58.6-73.6]）相比，加用西妥昔单抗的 CRT 组在第 24 周时无治疗失败的患者更少（121 例患者中有 119 例[76.9%，69.7-83.0]）。加用西妥昔单抗的 CRT 组中位总生存期也较短（22.1 个月[95%CI 15.1-24.5] vs 25.4 个月[20.5-37.9]；调整 HR 1.53[95%CI 1.03-2.27]；p=0.035）。接受 CRT 加西妥昔单抗治疗的患者有更多的非血液学 3 级或 4 级毒性（129 例患者中有 102 例[79%] vs 129 例患者中有 81 例[63%]；p=0.004）。最常见的 3 级或 4 级毒性为白细胞计数低（西妥昔单抗组 14 例[11%] vs 对照组 21 例[16%]）、中性粒细胞绝对计数低（西妥昔单抗组 15 例[12%] vs 对照组 24 例[19%]）、疲劳（西妥昔单抗组 26 例[20%] vs 对照组 25 例[19%]）和吞咽困难（西妥昔单抗组 35 例[27%] vs 对照组 37 例[29%]）。
在适合确定性 CRT 的食管癌患者中，西妥昔单抗不能被推荐加入标准化疗和放疗。
英国癌症研究中心。
