Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial
Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial
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DOI：
10.1016/s0140-6736(21)01123-5
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发表时间：
2021-07-22
期刊：
影响因子：
168.9
通讯作者：
Ma, Jun
中科院分区：
文献类型：
--
作者：
Chen, Yu-Pei;Liu, Xu;Ma, Jun
背景局部晚期鼻咽癌患者具有较高的疾病复发风险，尽管接受标准治疗（即，明确的同步放化疗伴或不伴诱导化疗）后获得完全临床缓解的患者比例较高。需要额外的辅助治疗来进一步降低复发和死亡的风险。然而，鼻咽癌辅助化疗的好处仍然存在争议，突出需要更有效的辅助治疗options.Methods这个多中心，开放标签，平行组，随机，对照，3期试验在14家医院在中国。患者（年龄18-65岁）经组织学证实的高危局部晚期鼻咽癌（III-IVA期，不包括T3- 4 N 0和T3 N1疾病），确定性放化疗后无局部疾病或远处转移，东部肿瘤协作组体能状态为0或1，血液学、肾和肝功能充足，在随机分组前12-16周接受了最后一次放疗剂量的患者被随机分配（1：1）接受口服节拍卡培他滨（650 mg/m2体表面积，每日两次，持续1年;节拍卡培他滨组）或观察（标准治疗组）。采用计算机生成的序列（区组大小为4）进行随机化，按试验中心和接受诱导化疗（是或否）分层。主要终点是无失败生存期，定义为意向治疗人群中从随机化至疾病复发（远处转移或局部复发）或任何原因导致的死亡的时间。在接受至少一剂卡培他滨或已开始观察的所有患者中评估安全性。该试验注册于ClinicalTrials.gov，NCT 02958111。结果在2017年1月25日至2018年10月25日期间，筛选了675例患者，其中406例入组并随机分配至节拍卡培他滨组（n=204）或标准治疗组（n=202）。中位随访38个月（IQR 33-42）后，节拍卡培他滨组有29例（14%）复发或死亡事件，标准治疗组有53例（26%）复发或死亡事件。节拍卡培他滨组的3年无失败生存率（85.3% [95%CI 80.4-90.6]）显著高于标准治疗组（75.7% [69.9-81.9]），分层风险比为0.50（95%CI 0.32- 0.79; p=0.0023）。节拍卡培他滨组201例患者中有35例（17%）报告了3级不良事件，标准治疗组200例患者中有11例（6%）报告了3级不良事件;手足综合征是卡培他滨相关的最常见不良事件（18例[9%]患者患有3级手足综合征）。一个（
Background Patients with locoregionally advanced nasopharyngeal carcinoma have a high risk of disease relapse, despite a high proportion of patients attaining complete clinical remission after receiving standard-of-care treatment (ie, definitive concurrent chemoradiotherapy with or without induction chemotherapy). Additional adjuvant therapies are needed to further reduce the risk of recurrence and death. However, the benefit of adjuvant chemotherapy for nasopharyngeal carcinoma remains controversial, highlighting the need for more effective adjuvant treatment options.Methods This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was done at 14 hospitals in China. Patients (aged 18-65 years) with histologically confirmed, high-risk locoregionally advanced nasopharyngeal carcinoma (stage III-IVA, excluding T3-4N0 and T3N1 disease), no locoregional disease or distant metastasis after definitive chemoradiotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, sufficient haematological, renal, and hepatic function, and who had received their final radiotherapy dose 12-16 weeks before randomisation, were randomly assigned (1:1) to receive either oral metronomic capecitabine (650 mg/m(2) body surface area twice daily for 1 year; metronomic capecitabine group) or observation (standard therapy group). Randomisation was done with a computer-generated sequence (block size of four), stratified by trial centre and receipt of induction chemotherapy (yes or no). The primary endpoint was failure-free survival, defined as the time from randomisation to disease recurrence (distant metastasis or locoregional recurrence) or death due to any cause, in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of capecitabine or who had commenced observation. This trial is registered with ClinicalTrials.gov, NCT02958111.Findings Between Jan 25, 2017, and Oct 25, 2018, 675 patients were screened, of whom 406 were enrolled and randomly assigned to the metronomic capecitabine group (n=204) or to the standard therapy group (n=202). After a median follow-up of 38 months (IQR 33-42), there were 29 (14%) events of recurrence or death in the metronomic capecitabine group and 53 (26%) events of recurrence or death in the standard therapy group. Failure-free survival at 3 years was significantly higher in the metronomic capecitabine group (85.3% [95% CI 80.4-90.6]) than in the standard therapy group (75.7% [69.9-81.9]), with a stratified hazard ratio of 0.50 (95% CI 0.32- 0.79; p=0.0023). Grade 3 adverse events were reported in 35 (17%) of 201 patients in the metronomic capecitabine group and in 11 (6%) of 200 patients in the standard therapy group; hand-foot syndrome was the most common adverse event related to capecitabine (18 [9%] patients had grade 3 hand-foot syndrome). One (