Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial
Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial
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DOI：
10.1016/s1470-2045(11)70320-5
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发表时间：
2012-02-01
期刊：
影响因子：
51.1
通讯作者：
Ma, Jun
中科院分区：
文献类型：
--
作者：
Chen, Lei;Hu, Chao-Su;Ma, Jun
背景 对于局部晚期鼻咽癌，在同步放化疗的基础上加用辅助化疗的效果尚不清楚。我们的目的是评估辅助化疗与单独同步放化疗相比对同步放化疗的贡献。方法我们在中国七个机构进行了一项开放标签3期多中心随机对照试验。随机化是由计算机生成的随机数代码进行的。患者按治疗中心分层并随机分配为四人一组。治疗分配没有被掩盖。我们将非转移性 III 期或 IV 期（T3-4N0 除外）鼻咽癌患者随机分配接受同步放化疗加辅助化疗或单独同步放化疗。两组患者每周接受 40 mg/m(2) 顺铂治疗，持续 7 周，同时进行放疗。放射治疗的剂量为每次 2.0-2.27 Gy，每周每日 5 次，持续 6-7 周，原发肿瘤总剂量为 66 Gy 或更高，受累颈部区域总剂量为 60-66 Gy。同步放化疗加辅助化疗组随后接受80 mg/m(2)辅助顺铂和800 mg/m(2)/天氟尿嘧啶，每4周120 h，共3个周期。我们的主要终点是无失败生存。我们对意向治疗人群进行了疗效分析。我们的审判正在进行中；在本报告中，我们介绍了 2 年生存结果和急性毒性效应。该试验在 ClinicalTrials.gov 注册，编号为 NCT00677118。结果 251 名患者被分配到同步放化疗加辅助化疗组，257 名患者被分配到单独同步放化疗组。中位随访时间为 37.8 个月（范围 1.3-61.0）后，同步放化疗加辅助化疗组的估计 2 年无失败生存率为 86%（95% CI 81-90），仅同步放化疗组为 84%（78-88）（风险比 0.74，95% CI 0.49-1.10； p=0.13）。口腔炎是放疗（同步放化疗加辅助化疗组 249 例患者中的 76 例，单独同步放化疗组 254 例患者中 82 例）和辅助化疗（接受辅助化疗的 205 例患者中的 43 例 [21%]）期间最常见的 3 级或 4 级不良事件。 解释 顺铂和氟尿嘧啶辅助化疗 并没有显着改善局部晚期鼻咽癌同步放化疗后的无失败生存率。需要更长时间的随访来全面评估生存率和晚期毒性作用，但目前此类方案不应在精心设计的临床试验之外使用。
Background The effect of the addition of adjuvant chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to assess the contribution of adjuvant chemotherapy to concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone.Methods We did an open-label phase 3 multicentre randomised controlled trial at seven institutions in China. Randomisation was by a computer-generated random number code. Patients were stratified by treatment centre and randomly assigned in blocks of four. Treatment allocation was not masked. We randomly assigned patients with non-metastatic stage III or IV (except T3-4N0) nasopharyngeal carcinoma to receive concurrent chemoradiotherapy plus adjuvant chemo therapy or concurrent chemoradiotherapy alone. Patients in both groups received 40 mg/m(2) cisplatin weekly up to 7 weeks, concurrently with radiotherapy. Radiotherapy was given as 2.0-2.27 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 Gy or greater to the primary tumour and 60-66 Gy to the involved neck area. The concurrent chemoradiotherapy plus adjuvant chemotherapy group subsequently received 80 mg/m(2) adjuvant cisplatin and 800 mg/m(2) per day fluorouracil for 120 h every 4 weeks for three cycles. Our primary endpoint was failure-free survival. We did efficacy analyses in our intention-to-treat population. Our trial is ongoing; in this report we present the 2 year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov, number NCT00677118.Findings 251 patients were assigned to the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 257 to the concurrent chemoradiotherapy alone group. After a median follow-up of 37.8 months (range 1.3-61.0), the estimated 2 year failure-free survival rate was 86% (95% CI 81-90) in the concurrent chemo radiotherapy plus adjuvant chemotherapy group and 84% (78-88) in concurrent chemoradiotherapy only group (hazard ratio 0.74, 95% CI 0.49-1.10; p=0.13). Stomatitis was the most commonly reported grade 3 or 4 adverse event during both radiotherapy (76 of 249 patients in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 82 of 254 in the concurrent chemoradiotherapy alone group) and adjuvant chemotherapy (43 [21%] of 205 patients treated with adjuvant chemotherapy).Interpretation Adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve failure-free survival after concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma. Longer follow-up is needed to fully assess survival and late toxic effects, but such regimens should not, at present, be used outside well-designed clinical trials.