替吉奥胶囊同步放化疗对比单纯放疗治疗老年食管癌患者的疗效：一项多中心随机 3 期临床试验。
Efficacy of Concurrent Chemoradiotherapy With S-1 vs Radiotherapy Alone for Older Patients With Esophageal Cancer: A Multicenter Randomized Phase 3 Clinical Trial.
机构信息
Department of Radiation Oncology, Cancer Hospital of the University of Chinese Academy of Science/Institute of Cancer and Basic Medicine, Chinese Academy of Science, Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, China.
The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Nanjing, China.
出版信息
JAMA Oncol. 2021 Oct 1;7(10):1459-1466. doi: 10.1001/jamaoncol.2021.2705.
IMPORTANCE
Most older patients with esophageal cancer cannot complete the standard concurrent chemoradiotherapy (CCRT). An effective and tolerable chemoradiotherapy regimen for older patients is needed.
OBJECTIVE
To evaluate the efficacy and toxic effects of CCRT with S-1 vs radiotherapy (RT) alone in older patients with esophageal cancer.
DESIGN, SETTING, AND PARTICIPANTS: A randomized, open-label, phase 3 clinical trial was conducted at 23 Chinese centers between June 1, 2016, and August 31, 2018. The study enrolled 298 patients aged 70 to 85 years. Eligible participants had histologically confirmed esophageal cancer, stage IB to IVB disease based on the 6th edition of the American Joint Committee on Cancer (stage IVB: only metastasis to the supraclavicular/celiac lymph nodes) and an Eastern Cooperative Oncology Group performance status of 0 to 1. Data analysis was performed from August 1, 2020, to March 10, 2021.
INTERVENTIONS
Patients were stratified according to age (<80 vs ≥80 years) and tumor length (<5 vs ≥5 cm) and randomly assigned (1:1) to receive either CCRT with S-1 or RT alone.
MAIN OUTCOMES AND MEASURES
The primary end point was the 2-year overall survival rate using intention-to-treat analysis.
RESULTS
Of the 298 patients enrolled, 180 (60.4%) were men. The median age was 77 (interquartile range, 74-79) years in the CCRT group and 77 (interquartile range, 74-80) years in the RT alone group. A total of 151 patients (50.7%) had stage III or IV disease. The CCRT group had a significantly higher complete response rate than the RT group (41.6% vs 26.8%; P = .007). Surviving patients had a median follow-up of 33.9 months (interquartile range: 28.5-38.2 months), and the CCRT group had a significantly higher 2-year overall survival rate (53.2% vs 35.8%; hazard ratio, 0.63; 95% CI, 0.47-0.85; P = .002). There were no significant differences in the incidence of grade 3 or higher toxic effects between the CCRT and RT groups except that grade 3 or higher leukopenia occurred in more patients in the CCRT group (9.5% vs 2.7%; P = .01). Treatment-related deaths were observed in 3 patients (2.0%) in the CCRT group and 4 patients (2.7%) in the RT group.
CONCLUSIONS AND RELEVANCE
In this phase 3 randomized clinical trial, CCRT with S-1 was tolerable and provided significant benefits over RT alone in older patients with esophageal cancer.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02813967.
目的：大多数老年食管癌患者无法完成标准的同期放化疗（CCRT）。需要一种对老年患者有效且耐受良好的放化疗方案。
背景：在 23 家中国中心进行了一项随机、开放标签、3 期临床试验，时间为 2016 年 6 月 1 日至 2018 年 8 月 31 日。研究纳入了 298 名年龄在 70 至 85 岁之间的患者。符合条件的参与者均经组织学证实患有食管癌，疾病分期为第 6 版美国癌症联合委员会（AJCC）的 IB 至 IVB 期（IVB 期：仅转移至锁骨上/腹腔淋巴结），东部肿瘤协作组（ECOG）体能状态为 0 至 1 分。数据分析于 2020 年 8 月 1 日至 2021 年 3 月 10 日进行。
患者：患者根据年龄（<80 岁与≥80 岁）和肿瘤长度（<5cm 与≥5cm）进行分层，并随机（1:1）分配至接受 S-1 联合 CCRT 或单纯放疗。
主要结局和措施：主要终点为意向治疗分析的 2 年总生存率。
结果：在 298 名入组患者中，180 名（60.4%）为男性。CCRT 组的中位年龄为 77 岁（四分位距，74-79 岁），单纯放疗组为 77 岁（四分位距，74-80 岁）。共有 151 名患者（50.7%）患有 III 或 IV 期疾病。CCRT 组完全缓解率明显高于单纯放疗组（41.6%比 26.8%；P=0.007）。生存患者的中位随访时间为 33.9 个月（四分位距：28.5-38.2 个月），CCRT 组 2 年总生存率明显更高（53.2%比 35.8%；风险比，0.63；95%CI，0.47-0.85；P=0.002）。除 CCRT 组白细胞减少症（3 级或以上）发生率较高（9.5%比 2.7%；P=0.01）外，CCRT 组和单纯放疗组的 3 级或以上毒性反应发生率无显著差异。在 CCRT 组和单纯放疗组中，分别有 3 名（2.0%）和 4 名（2.7%）患者发生治疗相关死亡。
结论：在这项 3 期随机临床试验中，与单纯放疗相比，S-1 联合 CCRT 对老年食管癌患者是可耐受的，并带来显著获益。
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