Xie Wei-Hao, Xiao Wei-Wei, Chang Hui, Xu Ming-Jun, Hu Yong-Hong, Zhou Tong-Chong, Zhong Qiong, Chen Chun-Yan, Lu Li-Xia, Wang Qiao-Xuan, Zhu Yu-Jia, Yang Jing, Shi Xing-Yuan, Kang Hua-Long, Wei Jia-Wang, Huang Rong, Peng Hai-Hua, Yuan Yan, Wu Shi-Hai, Jiang Xin-Hua, Liu Ya-Jie, Wen Bi-Xiu, Gao Yuan-Hong
State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China.
Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China.
BMJ. 2025 Apr 15;389:e081557. doi: 10.1136/bmj-2024-081557.
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.
Phase 3, multicentre, randomised controlled trial.
Six sites in China from 23 February 2016 to 18 February 2019.
186 participants aged ≤70 years with a diagnosis of untreated stage T1-4N2-3M0 nasopharyngeal carcinoma.
Participants were prospectively enrolled and randomly allocated to either the neoadjuvant chemotherapy plus concurrent chemoradiotherapy group (four cycles of neoadjuvant chemotherapy (docetaxel 75 mg/m on day 1 and cisplatin 37.5 mg/m on days 2-3, every 3 weeks) followed by concurrent chemoradiotherapy (intensity modulated radiotherapy plus weekly cisplatin 40 mg/m) or the concurrent chemoradiotherapy only group, in a 1:1 ratio.
Five year distant metastasis-free survival and overall survival were analysed using the intention-to-treat approach.
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%) 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.
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.
ClinicalTrials.gov NCT02512315.
通过评估远处转移的减少情况以及N2-3期鼻咽癌患者生存率的改善情况，比较四个周期多西他赛联合顺铂新辅助化疗后序贯同步放化疗与单纯同步放化疗的效果。
3期多中心随机对照试验。
2016年2月23日至2019年2月18日期间在中国的六个地点。
186名年龄≤70岁、诊断为未经治疗的T1-4N2-3M0期鼻咽癌患者。
前瞻性纳入参与者并随机分配到新辅助化疗加同步放化疗组（四个周期新辅助化疗（多西他赛75mg/m²第1天，顺铂37.5mg/m²第2 - 3天，每3周一次），随后序贯同步放化疗（调强放疗加每周顺铂40mg/m²））或单纯同步放化疗组，比例为1:1。
采用意向性分析方法分析五年无远处转移生存率和总生存率。
新辅助化疗加同步放化疗组和单纯同步放化疗组各分配93名参与者。中位随访时间76.9（四分位间距65.4 - 85.9）个月后，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%）对比78.2%（69.8%至86.6%）；风险比0.41（95%CI 0.19至0.87）；P = 0.02），五年总生存率也更高（90.3%（84.2%至96.4%）对比82.6%（75.0%至90.2%）；风险比0.38（0.18至0.82）；P = 0.01）。新辅助化疗加同步放化疗组和单纯同步放化疗组分别有60（65%）和46（51%）名患者出现3/4级急性毒性反应（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归因于3/4级中性粒细胞减少（43（47%）对比10（11%）；P < 0.001）。两组间在任何晚期毒性方面均未观察到显著差异，且新辅助化疗加同步放化疗组的参与者在入组五年后的生活质量往往更好。
四个周期多西他赛联合顺铂新辅助化疗后序贯同步放化疗可有效减少N2-3期鼻咽癌患者的远处转移并提高生存率，且毒性可控。
ClinicalTrials.gov NCT02512315
