Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Parel, Mumbai, India.
Department of Biostatistics, Tata Memorial Center, Homi Bhabha National Institute, Mumbai, India.
Esophagus. 2022 Oct;19(4):670-682. doi: 10.1007/s10388-022-00923-8. Epub 2022 May 26.
Improving outcomes in locally advanced esophageal/GEJ squamous cell cancer (SCC) is an unmet need. We investigated the addition of oral metronomic chemotherapy (OMC) following definitive chemoradiotherapy (CRT).
This was a randomized open-label integrated phase II/III study in patients with SCC of esophagus/GEJ following definitive CRT who had no radiologic evidence of progression, and no endoscopically detected disease. Randomization was 1:1 to OMC (celecoxib 200 mg twice daily and methotrexate 15 mg/m weekly) for 12 months or observation. The primary endpoint for the phase II portion was progression-free survival (PFS); secondary endpoints were overall survival (OS) and toxicity. P ≤ 0.2 for PFS was required to proceed to phase III.
Between Jan 2016 and Dec 2019, we enrolled 151 patients for the phase II portion, 75 to OMC and 76 to observation. The tumor originated in the upper thoracic esophagus in 79% patients. Concurrent CRT consisted of median 63 Gy in a median of 35 fractions; concurrent chemotherapy was weekly paclitaxel + carboplatin in 91%. OMC was started at a median of 2.6 months (IQR 2.3-2.8) from CRT completion. Grade 3 or higher toxicities occurred in 18 patients (24%) in the OMC arm and 9 (12%) in the observation arm; P = 0.071. Median PFS was 25 months (95% CI, 17-58) in the OMC arm and was not attained [NA] (95% CI, 25-NA) in the observation arm; HR, 1.51, 95% CI, 1-2; P = 0.073. Median OS was 36 months (95% CI, 23-NA) in the OMC arm, and not attained (95% CI, NA-NA) in the observation arm; HR, 1.77; 95% CI, 1-2.9; P = 0.023.
Oral metronomic methotrexate and celecoxib in patients who have not progressed radiologically and have no endoscopic evidence of disease following radical CRT for locally advanced esophageal/GEJ SCC does not improve outcomes and may lower survival. [Funded by the TMC-Research Administration Council (TRAC); CHROME study (CHemoRadiotherapy followed by Oral Metronomic therapy in Esophageal cancer); ctri.nic.in number: CTRI/2015/09/006204].
CTRI/2015/09/006204.
提高局部晚期食管/胃食管交界处（GEJ）鳞状细胞癌（SCC）的疗效是未满足的需求。我们研究了在根治性放化疗（CRT）后添加口服节拍化疗（OMC）的效果。
这是一项在接受根治性 CRT 后局部晚期 SCC 患者中进行的随机、开放标签的 II/III 期研究，这些患者无影像学进展证据，且无内镜检测到的疾病。患者按 1:1 随机分配至 OMC 组（塞来昔布 200mg，每日 2 次；甲氨蝶呤 15mg/m，每周 1 次）治疗 12 个月或观察组。II 期部分的主要终点是无进展生存期（PFS）；次要终点是总生存期（OS）和毒性。PFS 的 P 值≤0.2 时，可进入 III 期研究。
2016 年 1 月至 2019 年 12 月，我们共招募了 151 例患者入组 II 期研究，其中 75 例患者接受 OMC 治疗，76 例患者接受观察组治疗。肿瘤起源于上胸段食管的患者占 79%。同期 CRT 采用中位剂量 63Gy，共 35 次；同期化疗采用紫杉醇+卡铂每周方案的患者占 91%。OMC 于 CRT 完成后中位时间 2.6 个月（IQR 2.3-2.8）开始。OMC 组有 18 例（24%）患者发生 3 级或更高级别的毒性反应，观察组有 9 例（12%）患者发生该级别的毒性反应（P=0.071）。OMC 组的中位 PFS 为 25 个月（95%CI，17-58），观察组未达到（NA）（95%CI，25-NA）；HR 为 1.51，95%CI，1-2；P=0.073。OMC 组的中位 OS 为 36 个月（95%CI，23-NA），观察组未达到（95%CI，NA-NA）；HR 为 1.77；95%CI，1-2.9；P=0.023。
对于局部晚期食管/GEJ SCC 患者，在根治性 CRT 后未出现影像学进展且无内镜疾病证据的情况下，口服节拍化疗（甲氨蝶呤联合塞来昔布）并不能改善患者的预后，反而可能降低生存率。[由 TMC-Research Administration Council（TRAC）资助；CHROME 研究（根治性放化疗后口服节拍化疗治疗食管癌）；ctri.nic.in 注册号：CTRI/2015/09/006204]。
CTRI/2015/09/006204。
