局部晚期鼻咽癌调强放疗联合含奈达铂不同方案同期化疗的疗效分析

Clinical Outcomes of Concurrent Nedaplatin-based Chemotherapy and Intensity-modulated Radiotherapy for Locally Advanced Nasopharyngeal Carcinoma

[目的]评价调强放疗联合含奈达铂方案化疗治疗局部晚期鼻咽癌的临床疗效及不良反应。[方法]166例Ⅲ、Ⅳa期初治鼻咽癌患者接受调强放疗联合同期含奈达铂方案化疗。调强放疗采用鼻咽及全颈同步整合加量(SIB)技术,按两进程给予:鼻咽部剂量70Gy/32F,颈部淋巴结剂量66Gy/32F,颈部预防剂量高危区60Gy/32F、低危区50.4Gy/28F。放疗期间同步化疗2个周期,21d为1个周期。含奈达铂化疗方案分为3组:FP(5-氟尿嘧啶+奈达铂)58例;TP(紫杉醇+奈达铂)62例;TFP(紫杉醇+5-氟尿嘧啶+奈达铂)46例。分析比较3组患者的疗效和急性不良反应。[结果]166例患者全部按计划完成同期放化疗。中位随访43个月,FP组的4年总生存率、局部控制率、区域控制率及无远处转移生存率分别为81.5%、93.0%、98.2%、79.0%,TP组为81.7%、91.4%、96.8%、82.0%,TFP组为84.7%、90.8%、93.3%、81.9%。3组间比较总生存率(P=0.752)、局部控制率(P=0.961)、区域控制率(P=0.423)及无远处转移生存率(P=0.836)均无显著性差异。治疗相关不良反应主要为骨髓抑制、胃肠道反应、放射性口腔黏膜炎。3组患者Ⅲ～Ⅳ级急性不良反应发生率分别为17.2%vs22.6%vs41.3%,差异有显著性(P=0.016),TFP组较TP组及FP组发生率明显增加(P=0.037,P=0.007)。多因素分析结果表明N分期是影响患者总生存率(P=0.036)和无远处转移生存率(P=0.037)的独立预后因素。[结论]调强放疗联合同期含奈达铂方案化疗治疗局部晚期鼻咽癌,可获得较好肿瘤控制和生存率,患者顺应性好,反应可耐受。TFP三药方案较FP、TP两药方案急性不良反应的发生明显增加,临床疗效相近。N分期是影响预后的主要因素,远处转移是治疗失败的主要原因。

Purpose To evaluate the efficacy and toxicities of nedaplatin （NDP）-based chemotherapy concurrent with intensity-modulated radiotherapy （IMRT） in the treatment for patients with locally advanced nasopharyngeal carcinoma （NPC）. Methods One hundred and sixty-six locally advanced NPC patients with stage Ⅲ to Ⅳa received IMRT concurrent with NDP-based chemotherapy.Simutaneous integrated boost （SIB） technique to a whole field encompassing nasopharyngeal carcinoma and full neck were used in IMRT. The total prescription dose according to the two processes of IMRT was 70Gy/32F to gross target volume to nasopharynx （GTVnx）,66Gy/32F to positive neck lymph nodes （GTVnd）,60Gy/32F to clinical target volume 1 with high risk of metastasis （CTV1）,50.4Gy/28F to clinical target volume 2 with lower risk of metastasis（CTV2）.Two courses of NDP-based chemotherapy were delivered during radiotherapy, each for 21 days. Concurrent NDP-based chemotherapy were divided into three groups： FP group （5-fluorouracil＋NDP,n=58）,TP group （taxol＋NDP,n=62） and TFP group （taxol＋5-fluorouracil＋NDP,n=46）. The efficacy and acute toxicities of each group were analyzed. Results All patients completed concurrent chemo-radiotherapy. With a median follow-up of 43 months, the 4-year overall survival rates （OS）,local control （LC）,regional control （RC）,and distant metastasis-free survival（DMFS） were 81.5%,93.0%,98.2%,79.0% in FP group,81.7%,91.4%, 96.8%,82.0% in TP group,and 84.7%,90.8%,93.3%,81.9% in TFP group,respectively. However,no significant difference of OS （P=0.752）,LC （P=0.961）,RC （P=0.423） and DMFS （P=0.836） was observed in the three groups. The most common treatment-related toxicities includedmyelosuppression,gastrointestinal symptoms and oral mucositis. Those of grade Ⅲ ～ Ⅳ acute toxicities were 17.2%,22.6%,41.3% respectively,with significant difference in the three groups （P=0.016）. The TFP group experienced more grade Ⅲ～Ⅳ acute toxicities in comparing to TP or FP group（P=0.037,P=0.007）. Multivariate Cox regression analysis revealed that N-classification was an independent prognostic factor for OS（P=0.036） and DMFS （P=0.037）.Conclusion IMRT concurrent with NDP-based chemotherapy provide favorable local control and OS with strong compliance and acceptable toxicities for locally advanced NPC. TFP regimen shows a similar efficacy with TP or FP regimens in tumor control and overall survival,but with an increasing acute toxicities incidence. N-classification is the main influencing factor of prognosis,distant metastasis remains the most difficult treatment challenge for patients with locally advanced NPC.