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诱导多西他赛、铂类和氟尿嘧啶化疗对接受同步放化疗的III期或IVA/B期鼻咽癌患者的影响:两项平行的2期临床试验的最终结果

Effects of induction docetaxel, platinum, and fluorouracil chemotherapy in patients with stage III or IVA/B nasopharyngeal cancer treated with concurrent chemoradiation therapy: Final results of 2 parallel phase 2 clinical trials.

作者信息

Kong Lin, Zhang Youwang, Hu Chaosu, Guo Ye, Lu Jiade J

机构信息

Department of Radiation Oncology, Shanghai Proton and Heavy-Ion Center, Fudan University Shanghai Cancer Hospital, Shanghai, China.

Department of Radiation Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China.

出版信息

Cancer. 2017 Jun 15;123(12):2258-2267. doi: 10.1002/cncr.30566. Epub 2017 Feb 13.

Abstract

BACKGROUND

The effects of docetaxel, platinum, and fluorouracil (TPF) induction chemotherapy plus concurrent chemoradiotherapy (CCRT) on locoregionally advanced nasopharyngeal cancer (NPC) are unclear. This study examined the long-term outcomes of the addition of this regimen to CCRT for stage III and IVA/B NPC.

METHODS

Two parallel, single-arm phase 2 trials were performed synchronously to evaluate the efficacy and toxicity of TPF-based induction chemotherapy in patients with stage III or IVA/B NPC. The induction chemotherapy, which preceded standard intensity-modulated radiation therapy/platinum-based chemoradiation, consisted of 3 cycles of docetaxel (75 mg/m on day 1), cisplatin (75 mg/m on day 1), and a continuous infusion of fluorouracil (500 mg/m /d on days 1-5) every 4 weeks. The primary endpoint for both trials was 5-year overall survival (OS).

RESULTS

Between January 2007 and July 2010, 52 eligible patients with stage III NPC and 64 eligible patients with nonmetastatic stage IV NPC were accrued to the 2 trials. With a median follow-up of 67 months, the 5-year OS, progression-free survival, distant metastasis-free survival, and local progression-free survival (LPFS) rates were all improved in comparison with historical benchmarks for patients with stage III or IVA/IVB NPC. Multivariate analyses indicated that T and N classifications (T1/T2 vs T3/T4 and N3 vs N0-N2) were the only significant prognosticators for OS. The number of induction chemotherapy cycles was the only significant prognostic factor for predicting LPFS.

CONCLUSIONS

TPF-based induction chemotherapy appears to significantly improve outcomes in comparison with historical data when it is administered before CCRT for locoregionally advanced NPC. A phase 3 trial is currently being performed to confirm this benefit. Cancer 2017;123:2258-2267. © 2017 American Cancer Society.

摘要

背景

多西他赛、铂类和氟尿嘧啶(TPF)诱导化疗联合同步放化疗(CCRT)对局部晚期鼻咽癌(NPC)的影响尚不清楚。本研究探讨了将该方案添加到CCRT中用于III期和IVA/B期NPC的长期疗效。

方法

同步进行两项平行的单臂2期试验,以评估基于TPF的诱导化疗对III期或IVA/B期NPC患者的疗效和毒性。诱导化疗在标准调强放疗/铂类同步放化疗之前进行,每4周进行3个周期,具体为多西他赛(第1天75mg/m²)、顺铂(第1天75mg/m²),并持续输注氟尿嘧啶(第1 - 5天500mg/m²/天)。两项试验的主要终点均为5年总生存率(OS)。

结果

2007年1月至2010年7月,52例符合条件的III期NPC患者和64例符合条件的非转移性IV期NPC患者纳入这两项试验。中位随访67个月,与III期或IVA/IVB期NPC患者的历史基准相比,5年OS、无进展生存率、无远处转移生存率和无局部进展生存率(LPFS)均有所提高。多因素分析表明,T和N分类(T1/T2与T3/T4以及N3与N0 - N2)是OS的唯一显著预后因素。诱导化疗周期数是预测LPFS的唯一显著预后因素。

结论

与历史数据相比,基于TPF的诱导化疗在局部晚期NPC的CCRT之前应用时,似乎能显著改善预后。目前正在进行一项3期试验以证实这一益处。《癌症》2017年;123:2258 - 2267。©2017美国癌症协会

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