2025年4月15日，癌症医学协同创新中心Yuan-Hong Gao研究小组在《英国医学杂志》发表论文，研究了4个周期多西他赛联合顺铂作为新辅助化疗，然后同步放化疗治疗N2-3期鼻咽癌的疗效与安全性。

该研究旨在通过评估N2-3期鼻咽癌患者远处转移的减少和生存率的提高，比较多西他赛与顺铂作为新辅助化疗，然后同步放化疗和单独同步放化疗的四个周期的疗效。2016年2月23日至2019年2月18日，研究组在中国的六个地点进行了一项3期、多中心、随机对照试验。186名参与者年龄≤70岁、诊断为未经治疗的T1-4N2-3M0期鼻咽癌的参与者。

参与者被前瞻性招募并随机分配到新辅助化疗加同步放化疗组（四个周期的新辅助化疗（多西他赛75 mg/m²，第1天，顺铂37.5 mg/m²，每3周一次），然后进行同步放化疗（调强放疗加每周顺铂40 mg/m²），或仅进行同步放放疗组，比例为1:1。主要观察指标采用意向治疗方法分析五年无远处转移生存率和总生存率。

93名参与者被分配到新辅助化疗加同步放化疗和仅同步放化疗两组。在中位随访时间76.9个月（四分位数间距65.4-85.9）后，新辅助化疗加同步放化疗组的五年无远处转移生存率更高（91.3%（95%置信区间（CI）85.4%至97.2%），而78.2%（69.8%至86.6%）；危险比0.41（95%置信区间0.19至0.87）；P=0.02）和五年总生存率（90.3%（84.2%至96.4%）对82.6%（75.0%至90.2%）；危险比为0.38（0.18至0.82）；P=0.01）。

在新辅助化疗加同步放化疗和仅同步放化疗组中，分别有60名（65%）和46名（51%）患者观察到3/4级急性毒性（P=0.05）。新辅助化疗加同步放化疗组观察到的较高急性毒性主要是由于3/4级中性粒细胞减少症（43（47%）v 10（11%）；P<0.001）。两组之间没有观察到任何晚期毒性的显著差异，新辅助化疗加同步放化疗组的参与者在入组五年后往往有更好的生活质量。

研究结果表明，多西他赛联合顺铂新辅助化疗加同步放化疗四个周期可有效减少N2-3期鼻咽癌患者的远处转移，提高生存率，毒副反应可控。

附：英文原文

Title: Four cycles of docetaxel plus cisplatin as neoadjuvant chemotherapy followed by concurrent chemoradiotherapy in stage N2-3 nasopharyngeal carcinoma: phase 3 multicentre randomised controlled trial

Author: Wei-Hao Xie, Wei-Wei Xiao, Hui Chang, Ming-Jun Xu, Yong-Hong Hu, Tong-Chong Zhou, Qiong Zhong, Chun-Yan Chen, Li-Xia Lu, Qiao-Xuan Wang, Yu-Jia Zhu, Jing Yang, Xing-Yuan Shi, Hua-Long Kang, Jia-Wang Wei, Rong Huang, Hai-Hua Peng, Yan Yuan, Shi-Hai Wu, Xin-Hua Jiang, Ya-Jie Liu, Bi-Xiu Wen, Yuan-Hong Gao

Issue&Volume: 2025/04/15

Abstract:

Objective To compare the effects of four cycles of docetaxel with cisplatin as a neoadjuvant chemotherapy followed by concurrent chemoradiotherapy with concurrent chemoradiotherapy alone by assessing reductions in distant metastasis and improvements in survival in patients with stage N2-3nasopharyngeal carcinoma.

Design Phase 3, multicentre, randomised controlled trial.

Setting Six sites in China from 23 February 2016 to 18 February 2019.

Participants 186 participants aged ≤70 years with a diagnosis of untreated stage T1-4N2-3M0 nasopharyngeal carcinoma.

Intervention Participants were prospectively enrolled and randomly allocated to either the neoadjuvant chemotherapy plus concurrent chemoradiotherapy group (four cycles of neoadjuvant chemotherapy (docetaxel 75 mg/m2 on day 1 and cisplatin 37.5 mg/m2 on days 2-3, every 3 weeks) followed by concurrent chemoradiotherapy (intensity modulated radiotherapy plus weekly cisplatin 40 mg/m2) or the concurrent chemoradiotherapy only group, in a 1:1 ratio.

Main outcome measures Five year distant metastasis-free survival and overall survival were analysed using the intention-to-treat approach.

Results 93 participants were assigned to each of the neoadjuvant chemotherapy plus concurrent chemoradiotherapy and concurrent chemoradiotherapy only groups. After a median follow-up time of 76.9 (interquartile range 65.4-85.9) months, the neoadjuvant chemotherapy plus concurrent chemoradiotherapy group had superior five year distant metastasis-free survival (91.3% (95% confidence interval (CI) 85.4% to 97.2%) versus 78.2% (69.8% to 86.6%); hazard ratio 0.41 (95% CI 0.19 to 0.87); P=0.02) and five year overall survival (90.3% (84.2% to 96.4%) versus 82.6% (75.0% to 90.2%); hazard ratio 0.38 (0.18 to 0.82); P=0.01). Grade 3/4 acute toxicities were observed in 60 (65%) and 46 (51%) patients in the neoadjuvant chemotherapy plus concurrent chemoradiotherapy and concurrent chemoradiotherapy only groups, respectively (P=0.05). The higher acute toxicity observed in the neoadjuvant chemotherapy plus concurrent chemoradiotherapy group was primarily due to grade 3/4 neutropenia (43 (47%) v 10 (11%); P<0.001). No significant difference in any late toxicity was observed between the two groups, and participants in the neoadjuvant chemotherapy plus concurrent chemoradiotherapy group tended to have a better quality of life five years after enrolment.

Conclusions Four cycles of docetaxel plus cisplatin neoadjuvant chemotherapy with concurrent chemoradiotherapy can effectively reduce distant metastasis and improve survival for patients with stage N2-3 nasopharyngeal carcinoma with manageable toxicities.

DOI: 10.1136/bmj-2024-081557

Source: https://www.bmj.com/content/389/bmj-2024-081557