局部晚期鼻咽癌不同化疗方案配合 IMRT多中心前瞻性随机对照研究

A multicenter, prospective, randomized study of intensity-modulated radiother apy combined with different chemotherapy regimens for locally advanced nasopharyngeal carcinoma

目的：评价局部晚期鼻咽癌奈达铂联合多西他赛诱导化疗＋奈达铂同期 IMRT 与顺铂的疗效及不良反应。方法2011—2012年间5个治疗中心共223例经病理确诊的初治局部晚期鼻咽癌患者被随机分为两组，试验组113例采用多西他赛（65 mg／ m2第1天）＋奈达铂（80 mg／ m2第1天）诱导化疗2周期，奈达铂（40 mg／ m2第1天）每周方案同期 IMRT；对照组110例采用相同方案诱导化疗2周期，IMRT 顺铂（40 mg／ m2第1天）每周方案同期 IMRT。 Kaplan.Meier 计算生存率并 Logrank 检验两组差异，不良反应行 z 检验。结果随访率为99.1％。治疗结束后3个月两组有效率均为100％，试验和对照组2年LRFS、RRFS、DMFS、OS 分别为94.0％和93.4％、94.2％和94.1％、88.2％和86.7％、90.3％和87.3％（P＝0.757、0.478、0.509、0.413）；试验组白细胞、中性粒细胞、血小板减少发生率及严重程度较对照组高（P＝0.027、0.028、0.035），血红蛋白减少发生率及严重程度低于对照组（P＝0.000）；试验组恶心、呕吐发生率及程度低于对照组（P＝0.023），两组口腔黏膜炎、口干发生率相近（P＝0.483、0.781）。结论局部晚期鼻咽癌奈达铂联合多西他赛诱导化疗＋奈达铂同期 IMRT的近期疗效与顺铂的相似，胃肠道反应轻患者可耐受，但其骨髓抑制较重使用时应密切监测。

Objective To evaluate the efficacy and toxicity of induction chemotherapy with nedaplatin and docetaxel plus concurrent intensity.modulated radiotherapy （ IMRT） with nedaplatin or cisplatin in the treatment of locally advanced nasopharyngeal carcinoma （NPC）. Methods A total of 223 patients with pathologically diagnosed locally advanced NPC in five treatment centers from 2011 to 2012 were randomly divided into two groups. In the test group, one hundred and thirteen patients received two cycles of induction chemotherapy with docetaxel （65 mg/ m2 on day 1） and nedaplatin （80 mg/ m2 on day 1） plus concurrent IMRT with nedaplatin （40 mg/ m2 on day 1）. In the control group, 110 patients received two cycles of induction chemotherapy with the same regimens plus concurrent IMRT with cisplatin （40 mg/ m2 on day 1）. The survival rates were calculated with the Kaplan.Meier method and the differences in the survival rates between the two groups were analyzed using the log.rank test. Comparison of the incidence rates of adverse reactions between the two groups was made by the chi.square test. Results The follow.up rate was 99. 1%.The response rates at 3 months after treatment in the two groups were both 100%. The 2.year local recurrence.free, regional recurrence.free, distant metastasis.free, and overall survival rates were 94. 0%, 94. 2%, 88. 2%, and 90. 3%, respectively, in the test group, versus 93. 4%, 94. 1%, 86. 7%, and 87. 3% in the control group （ P= 0. 757、 0. 478、 0. 509、 0. 413）. The incidence rates and severity of leucopenia, neutropenia, and thrombocytopenia were significantly higher in the test group than in the control group （ P= 0. 027 , 0. 028 , 0. 035 ） . The incidence rates and severity of hemoglobin reduction and nausea /vomiting were significantly lower in the test group than in the control group （P= 0. 000,0. 023）. There were no significant differences in the incidence rates of mucositis and xerostomia between the two groups （ P=0. 483,0. 781）. Conclusions The short.term efficacy of induction chemotherapy with nedaplatin and docetaxel plus concurrent IMRT with nedaplatin is similar to that with cisplatin in the treatment of locally advanced NPC. The mild gastrointestinal reactions can be tolerated by patients. However, the severe myelosuppression should be closely monitored during the treatment.