添加贝伐珠单抗到标准放化疗治疗局部晚期鼻咽癌（RTOG 0615）：一项 2 期多机构试验。
Addition of bevacizumab to standard chemoradiation for locoregionally advanced nasopharyngeal carcinoma (RTOG 0615): a phase 2 multi-institutional trial.
机构信息
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
出版信息
Lancet Oncol. 2012 Feb;13(2):172-80. doi: 10.1016/S1470-2045(11)70303-5. Epub 2011 Dec 15.
BACKGROUND
We aimed to improve the outcomes for locoregionally advanced nasopharyngeal carcinoma by testing the feasibility and safety of the addition of bevacizumab to chemoradiotherapy.
METHODS
We enrolled patients older than 18 years with stage IIB-IVB nasopharyngeal carcinoma from 19 centres in North America and Hong Kong. Treatment consisted of three cycles of bevacizumab (15 mg/kg) and cisplatin (100 mg/m(2)) both given on days 1, 22, and 43 of radiation (70 Gy) with intensity-modulated radiation therapy delivered over 33 days on a daily basis, Monday through Friday. Patients then received three cycles of bevacizumab (15 mg/kg) and cisplatin (80 mg/m(2)), both given on days 64, 85, and 106 after radiation, and three cycles of fluorouracil (1000 mg/m(2) per day), given on days 64-67, 85-88, and 106-109 after radiation. The primary endpoint was the occurrence of treatment-related grade 4 haemorrhage or any grade 5 adverse event in the first year. Analyses were done with all eligible patients who started protocol treatment. The trial is registered at ClinicalTrials.gov, number NCT00408694.
FINDINGS
From Dec 13, 2006, to Feb 5, 2009, we enrolled 46 patients, of whom 44 were eligible for analysis. We recorded no grade 3-4 haemorrhages or grade 5 adverse events; nine patients (20%) had a treatment-related grade 1-2 haemorrhage. Nine patients had one or more grade 4 blood or bone marrow-related complication (grade 4 leucopenia was noted in six patients, grade 4 lymphopenia in five, grade 4 neutrophils in five, and grade 4 anaemia in one). One patient had two grade 4 infections with grade 3-4 neutrophils. One patient reported grade 4 tinnitus, one patient reported grade 4 thrombosis, one reported grade 4 radiation mucositis, and two reported grade 4 pharyngolaryngeal pain. With a median follow-up of 2·5 years (IQR 2·1-2·9), the estimated 2 year locoregional progression-free interval was 83·7% (95% CI 72·6-94·9), the 2 year distant metastasis-free interval was 90·8% (82·2-99·5), the 2 year progression-free survival was 74·7% (61·8-87·6), and 2 year overall survival was 90·9% (82·3-99·4).
INTERPRETATION
The addition of bevacizumab to standard chemoradiation treatment for patients with nasopharyngeal carcinoma is feasible, and might delay the progression of subclinical distant disease.
FUNDING
National Cancer Institute, USA.
背景
我们旨在通过检测贝伐单抗联合放化疗治疗局部晚期鼻咽癌的可行性和安全性来改善患者的预后。
方法
我们招募了来自北美和香港 19 个中心的年龄在 18 岁以上的 IIB-IVB 期鼻咽癌患者。治疗包括三个周期的贝伐单抗（15mg/kg）和顺铂（100mg/m2），均在放疗（70Gy）的第 1、22 和 43 天给予，在 33 天内每天给予强度调制放射治疗，周一至周五。然后，患者接受三个周期的贝伐单抗（15mg/kg）和顺铂（80mg/m2）治疗，均在放疗后第 64、85 和 106 天给予，以及三个周期的氟尿嘧啶（1000mg/m2/天）治疗，均在放疗后第 64-67、85-88 和 106-109 天给予。主要终点是在第一年发生治疗相关的 4 级出血或任何 5 级不良事件。所有开始方案治疗的合格患者均进行了分析。该试验在 ClinicalTrials.gov 上注册，编号为 NCT00408694。
结果
从 2006 年 12 月 13 日至 2009 年 2 月 5 日，我们共招募了 46 名患者，其中 44 名符合分析条件。我们没有记录到 3-4 级出血或 5 级不良事件；9 名患者（20%）出现了治疗相关的 1-2 级出血。9 名患者出现了一种或多种 4 级血液或骨髓相关并发症（6 名患者出现了 4 级白细胞减少，5 名患者出现了 4 级淋巴细胞减少，5 名患者出现了 4 级中性粒细胞减少，1 名患者出现了 4 级贫血）。1 名患者出现了两次 4 级感染，伴有 3-4 级中性粒细胞减少。1 名患者出现了 4 级耳鸣，1 名患者出现了 4 级血栓，1 名患者出现了 4 级放射性粘膜炎，2 名患者出现了 4 级咽喉痛。中位随访时间为 2.5 年（IQR 2.1-2.9），估计 2 年局部区域无进展间隔为 83.7%（95%CI 72.6-94.9），2 年远处无转移间隔为 90.8%（82.2-99.5），2 年无进展生存率为 74.7%（61.8-87.6），2 年总生存率为 90.9%（82.3-99.4）。
结论
贝伐单抗联合标准放化疗治疗鼻咽癌是可行的，可能会延迟亚临床远处疾病的进展。
资金来源
美国国立癌症研究所。
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