Ⅲ、Ⅳa期鼻咽癌调强放疗联合三种含铂方案同期化疗的初步研究

A preliminary study on Intensity-modulated radiation therapy with three platinum-based concurrent chemotherapyfor stage Ⅲ、Ⅳa stage nasopharyngeal carcinoma

目的:比较适形调强放射治疗(IMRT)联合顺铂+氟尿嘧啶(PF)、紫杉醇+顺铂(TP)、每周顺铂(DDP)方案同期治疗Ⅲ、Ⅳa期鼻咽癌的临床疗效和毒副反应。方法:采用前瞻、随机对照研究,138例经病理学证实的Ⅲ、Ⅳa期初治鼻咽癌患者随机分为PF组、TP组、DDP组,分别行PF、TP、每周顺铂方案同期放化疗。三组均采用IMRT放疗技术。结果:三组各入组46例,138例患者全部按计划完成治疗。至中位随访时间28(5～37)个月,PF组、TP组、DDP组1年、2年无瘤累积生存率分别为95.65%、91.30%、97.83%;91.30%、73.52%、97.83%。1年、2年累积生存率分别为97.83%、93.48%、100%;93.14%、78.68%、97.83%。三组无瘤生存曲线和生存曲线比较P<0.05。两两比较,TP组与PF组、TP组与DDP组P<0.05,PF组与DDP组P>0.05。三组发生Ⅲ～Ⅳ度粒细胞减少、Ⅲ～Ⅳ度胃肠道反应、Ⅲ～Ⅳ度口腔粘膜炎分别为34.78%vs 30.43%vs 8.70%、23.91%vs 21.74%vs 34.78%、60.87%vs 65.22%vs 52.17%。对三组Ⅲ～Ⅳ度粒细胞减少反应发生率进行两两比较,PF组与DDP组、TP组与DDP组P<0.01,PF组与TP组P>0.05。对三组Ⅲ～Ⅳ度胃肠道反应发生率进行两两比较,P>0.05,三组无差异。结论:IMRT同期联合PF、TP、DDP方案治疗Ⅲ、Ⅳa期鼻咽癌,近期疗效DDP、PF方案优于TP方案,Ⅲ～Ⅳ度粒细胞下降发生率DDP方案优于PF、TP方案,Ⅲ～Ⅳ度胃肠道反应和口腔粘膜炎的发生率三种方案无差别。远期疗效仍有待进一步随访观察比较。

Objective：To compare the response rate and toxicity of cisplatin plus fluorouracil （PF） ,paclitaxel plus cispla- tin （TP）or weekly cisplatin （DDP） concurrent chemotherapy with intensity modulated conformal radiotherapy （IMRT） in the treatment of patients with stage Ⅲ、Ⅳa nasopharyngeal carcinoma. Methods：Using the prospective randomized con- trolled study, 138 patients with stage Ⅲ-Ⅳa nasopharyngeal carcinoma diagnosed pathologically and first treated were randomized into the PF,TP or DDP groups, and received IMRT combined with two cycles of concurrent chemoradiotherapy with PF,TP or DDP regimen. Results： 138 cases were randomly divided into the PF,TP,and DDP groups. All the patients finished the treatment. Median follow-up for 28 （ 5 ~ 37 ） months later, the 1,2 year disease free survival rate of the PF ,TP and DDP group were 95.65% vs 91.30% vs 97.83% ,91.30% vs 78.12% vs 97.83% respectively;the 1,2 year over- all survival rate were 97.83% vs 93.48% vs 100% ,93.14% vs 78.68% vs 97.83% respectively. There were statistical significant differences of the tumor-free survival curves and survival curve in the three groups. In the pairwise comparison with the TP and PF group or the TP and DDP weekly group, there were significant difference （ P 〈0. 05 ）, and there was no significant difference between the PF and DDP weekly groups. The main toxicities were neutrophilic granuloaytopenia, gastrointestinal reactions and oral mucositis. The rate of Ⅲ-Ⅳ degree of the neutrophilic granuloaytopenia, gastrointesti- nal reactions and oral mucositis were 34.78% vs 30.43% vs 8.70% ,23.91% vs 21.74% vs 34.78% ,60.87% vs 65.22% vs 52.17%. In the pairwise comparison of the rate of IU - IV degree of the neutrophilic granuloaytopenia,there were significant statistic differences between the PF and DDP weekly group or the TP and DDP weekly group（P 〈 0.01 ）.There were no significant statistic differences between each group （ P 〉 0.05 ） ofⅢ-Ⅳ degree of gastrointestinal reac- tions. Conclusion： IMRT with the weekly DDP or PF group concurrent chemotherapy were better than the TP group in the short-term effect and the DDP group reduced the incidence of Ⅲ-Ⅳneutrophilic granuloaytopenia compared with the PF or TP group, there was not significant difference of the Ⅲ-Ⅳ degree oral mucositis and gastrointestinal reactions in the three groups. These regimes need further clinical research to confirm their long-term outcome.