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.

Methods

Phase 3, multicentre, randomised controlled trial.

第三阶段、多中心、随机对照试验。

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

2016年2月23日至2019年2月18日，中国六个研究中心。

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

186名年龄≤70岁的参与者，被诊断为未治疗的T1-4N2-3M0期鼻咽癌患者。

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.

参与者被前瞻性地纳入并随机分配到新辅助化疗联合同步放化疗组（每3周进行4个周期的新辅助化疗（多西他赛75 mg/m2在第1天，顺铂37.5 mg/m2在第2-3天），随后进行同步放化疗（调强放疗加每周顺铂40 mg/m2））或仅同步放化疗组，比例为1:1。

Methods

Five year distant metastasis-free survival and overall survivalwere analysed using the intention-to-treatapproach.

使用意向治疗分析法分析了五年无远处转移生存率和总生存率。

Results

93 participants were assigned to each of the neoadjuvant chemotherapy plus concurrent chemoradiotherapy and concurrent chemoradiotherapy only groups.

93名参与者被分配到新辅助化疗加同步放化疗组和仅同步放化疗组。

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 ratio0.41 (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 ratio0.38 (0.18 to 0.82); P=0.01).

经过中位随访时间76.9（四分位数间距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）和五年总生存率（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）。

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).

在新辅助化疗加同步放化疗组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）。

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).

在新辅助化疗加同步放化疗组观察到的更高急性毒性主要是由于3/4级中性粒细胞减少症（43名（47%）对10名（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.

两组之间未观察到任何晚期毒性差异，且接受新辅助化疗加同步放化疗的参与者在入组五年后的生活质量倾向于更好。

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.

四周期的多西他赛加顺铂新辅助化疗与同步放化疗可以有效减少远处转移并改善N2-3期鼻咽癌患者的生存率，毒性反应可控。

trial_registration

ClinicalTrials.gov NCT02512315.

临床试验注册号 NCT02512315。