中山大学马骏教授团队研究了卡培他滨节拍辅助治疗局部晚期鼻咽癌的疗效。相关论文于2021年6月7日发表于《柳叶刀》杂志上。
局部晚期鼻咽癌患者有很高的疾病复发风险，尽管有很高比例的患者在接受标准护理治疗后获得完全临床缓解。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，鼻咽癌辅助化疗的临床益处仍然存在争议，这提醒人们需要更有效的辅助治疗方案。
研究组在中国的14家医院进行了一项多中心、开放标签、平行组、随机、对照、临床3期试验，招募组织学确诊的高危局部晚期鼻咽癌患者，年龄为18-65岁，经明确放化疗后无局部病变或远处转移，东部肿瘤合作组表现状态为0或1，血液学和肝肾功能良好，随机分组前12-16周接受最终放疗剂量。
将患者按1：1随机分配，分别接受卡培他滨节拍化疗或标准治疗。主要终点是意向治疗人群中的无失败生存期，定义为从随机分组到疾病复发（远端转移或局部复发）或全因死亡的时间。对所有接受至少一剂卡培他滨或已开始观察的患者进行安全性评估。
2017年1月25日至2018年10月25日，研究组共筛查了675例患者，最终纳入406例，随机分组后卡培他滨节拍化疗组204例，标准治疗组202例。中位随访38个月后，卡培他滨节拍化疗组有29例（14%）患者复发或死亡，标准治疗组有53例（26%）。卡培他滨节拍化疗组的3年无失败生存率为85.3%，显著高于标准治疗组的75.7%。
卡培他滨节拍化疗组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%）；手足综合征是卡培他滨相关最常见的不良事件，有9%的患者发生。卡培他滨节拍化疗组有1例（<1%）患者出现4级中性粒细胞减少。两组均未报告治疗相关死亡。
研究结果表明，对于高危局部晚期鼻咽癌患者，在同步放化疗中加入卡培他滨节拍化疗显著改善了无失败生存期，且安全性可控。这些结果支持节拍化疗作为鼻咽癌辅助治疗的潜在获益。
附：英文原文
Title: Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial
Author: Yu-Pei Chen, Xu Liu, Qin Zhou, Kun-Yu Yang, Feng Jin, Xiao-Dong Zhu, Mei Shi, Guo-Qing Hu, Wei-Han Hu, Yan Sun, Hong-Fen Wu, Hui Wu, Qin Lin, Hui Wang, Ye Tian, Ning Zhang, Xi-Cheng Wang, Liang-Fang Shen, Zheng-Zheng Liu, Jing Huang, Xiu-Ling Luo, Ling Li, Jian Zang, Qi Mei, Bao-Min Zheng, Dan Yue, Jing Xu, San-Gang Wu, Yan-Xia Shi, Yan-Ping Mao, Lei Chen, Wen-Fei Li, Guan-Qun Zhou, Rui Sun, Rui Guo, Yuan Zhang, Cheng Xu, Jia-Wei Lv, Ying Guo, Hui-Xia Feng, Ling-Long Tang, Fang-Yun Xie, Ying Sun, Jun Ma
Issue&Volume: 2021-06-07
Abstract:
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/m2 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 (<1%) patient in the metronomic capecitabine group had grade 4 neutropenia. No treatment-related deaths were reported in either group.
Interpretation
The addition of metronomic adjuvant capecitabine to chemoradiotherapy significantly improved failure-free survival in patients with high-risk locoregionally advanced nasopharyngeal carcinoma, with a manageable safety profile. These results support a potential role for metronomic chemotherapy as an adjuvant therapy in the treatment of nasopharyngeal carcinoma.
DOI: 10.1016/S0140-6736(21)01123-5
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01123-5/fulltext
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投稿链接：http://ees.elsevier.com/thelancet
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