局部区域晚期鼻咽癌同期放化疗联合辅助化疗的前瞻性Ⅲ期临床研究

A Prospective Randomized Trial of Concurrent Chemoradiotherapy plus Adjuvant Chemotherapy in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma

目的:探讨同期放、化疗联合辅助化疗对鼻咽癌高发区人群的疗效。方法:选取中山大学肿瘤防治中心2002年7月至2005年9月316例非角化型或未分化型鼻咽癌,第五版AJCC分期为Ⅲ～ⅣB的患者入组。将患者随机分为单纯放疗组(对照组)和同期放、化疗联合辅助化疗组(试验组)。两组均采用根治性常规分割放疗。试验组患者在放疗期间同时给予Cisplatin 40mg/m2,d1,1次/周,连续7次,放疗结束后1个月开始辅助化疗,采用Cisplatin 80mg/m2,d1,5-FU 800mg/m2,d1～5,1次/4周,共3个疗程。结果采用意向性分析,比较两组疗效、治疗毒性及顺应性。结果:两组病例的主要预后因素包括性别、年龄、活动状态、分期方法及临床分期等,均具有可比性。试验组68.4%的患者完成了7个疗程同期化疗,84.2%的患者完成了6个疗程以上同期化疗,91.1%的患者完成了5个疗程以上同期化疗,61.4%的患者完成了3个疗程辅助化疗。试验组和对照组3级以上急性毒副反应为62.6%vs32.3%(P=0.000)。试验组和对照组2年总生存率、无瘤生存率、无远处转移生存率及无局部区域复发生存率分别为89.8%vs79.7%(P=0.003),84.6%vs72.5%(P=0.001),86.5%vs78.7%(P=0.024)及98.0%vs91.9%(P=0.007)。结论:在鼻咽癌高发区,同期放、化疗联合辅助化疗可提高局部区域晚期鼻咽癌患者总生存率、无瘤生存率、无远处转移生存率及无局部区域复发生存率,长期疗效有待进一步随访证实。

Objective： A prospective randomized trial was performed to evaluate the efficacy of concurrent chemora-diotherapy and adjuvant chemotherapy in patients with Iocoregionally advanced nasopharyngeal carcinoma （NPC） in endemic regions of China. Methods： Between July 2002 and September 2005, 316 eligible patients that had non-keratinizing or undifferentiated NPC and were classified as stage Ⅲ-ⅣB by the AJCC 5th Edition were enrolled in the study. The patients were treated with radiotherapy alone （RT） or concurrent chemoradio-therapy plus adjuvant chemotherapy （CRT）. All patients were treated by definitive-intent radiation therapy. The CRT patients received concurrent Cisplatin （40 mg/m^2 on day 1） weekly during RT, followed by Cisplatin （80 mg/m^2 on day 1） and Fluorouracil （800 mg/m^2 on days 1 to 5） every 4 weeks for 3 cycles after completion of RT. All patients were assessed by intent-to-treat analysis. The overall survival （OS） rates, failure-free survival （FFS） rates, distant failure-free survival （D-FFS） rates, and Iocoregional failure-free survival （LR-FFS） rates were compared. The toxicity of the regimen and the patient reponse to it were evaluated. Results： The two groups were well balanced in the distribution of all prognostic factors and RT parameters, such as sex, age, performance status, staging method and clinical stage. The CRT group experienced significantly more acute toxicities （62.6% vs. 32.3%, P=0.000）. There were 107 patients （68.4%） who completed all 7 cycles of concurrent chemotherapy, 84.2% of which had 6 cycles or more while 91% completed 5 cycles or more. Ninety-seven patients （61.4%） completed all 3 cycles of adjuvant chemotherapy. The 2-year OS rate was 89.8% for the CRT group, and 79.7% for the RT group （P=0.003）. The FFS rate was 84.6% for the CRT group, and 72.5% for the RT group （P=-0.001）. The D-FFS rate was 86.5% for the CRT group, and 78.7% for the RT group （P= 0.024）, while the LR-FFS rate for the CRT group was 98.0%, compared with 91.9% for the RT group （P= 0.007）. Conclusion： In patients with Iocoregionally advanced NPC in endemic regions of China, concurrent chemoradiotherapy plus adjuvant chemotherapy can improve the OS rate, FFS rate, D-FFS rate and LR-FFS rate. Further study is needed to confirm this effect.