Whole-Brain Radiation Therapy Plus Concomitant Temozolomide for the Treatment of Brain Metastases From Non-Small-Cell Lung Cancer: A Randomized, Open-Label Phase II Study
Whole-Brain Radiation Therapy Plus Concomitant Temozolomide for the Treatment of Brain Metastases From Non-Small-Cell Lung Cancer: A Randomized, Open-Label Phase II Study
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DOI：
10.3816/clc.2010.n.022
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发表时间：
2010-05-01
影响因子：
3.6
通讯作者：
Throuvalas, Nikolaos
中科院分区：
文献类型：
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作者：
Chua, Daniel;Krzakowski, Maciej;Throuvalas, Nikolaos
背景资料：先前发表的一项替莫唑胺联合全脑放射治疗（WBRT）的研究报告，在主要来自肺癌的脑转移患者中，与单用WBRT相比，缓解率显著改善，总生存率无显著改善趋势。本研究旨在证实在WBRT基础上加用替莫唑胺治疗伴有脑转移的非小细胞肺癌（NSCLC）患者的获益。患者与方法：由于入组情况较差，该计划的III期研究（目标= 380起事件）转换为II期研究（目标= 70起事件）。NSCLC和>= 1个新诊断的脑病变患者随机接受WBRT（30戈伊，分10次）单独治疗或联合替莫唑胺（75 mg/m2/d）治疗21或28天。终点包括总生存期和中枢神经系统（CNS）进展时间。结果如下：WBRT +替莫唑胺组（n = 47）的中位总生存期和至CNS进展的中位时间分别为4.4和3.1个月，WBRT组（n = 48）为5.7和3.8个月。然而，接受既往化疗的患者和同时发生脑转移的患者的百分比存在不平衡。在WBRT基础上加用替莫唑胺可增加恶心、呕吐、脱发、疲乏、厌食和便秘的发生率。大多数不良事件为轻度至中度。结论：在WBRT中添加替莫唑胺的益处尚未得到证实;然而，计划的III期试验的累积目标尚未达到，并且研究方案与先前使用的方案不同。因此，替莫唑胺在治疗脑转移瘤中的作用仍然没有得到解决。
Background: A previously published study of temozolomide concurrent with whole-brain radiation therapy (WBRT) reported significant improvement in response rates and a nonsignificant trend toward improved overall survival compared with WBRT alone in patients with brain metastases primarily from lung cancer. This study sought to confirm the benefit of adding temozolomide to WBRT in patients with non-small-cell lung cancer (NSCLC) with brain metastases. Patients and Methods: This planned phase III study (target = 380 events) was converted to a phase II study (target = 70 events) because of poor enrollment. Patients with NSCLC and >= 1 newly diagnosed brain lesion were randomized to WBRT (30 Gy in 10 fractions) alone or combined with temozolomide (75 mg/m(2)/day) for 21 or 28 days. Endpoints included overall survival and time to central nervous system (CNS) progression. Results: Median overall survival and median time to CNS progression was 4.4 and 3.1 months in the WBRT + temozolomide arm (n = 47) versus 5.7 and 3.8 months in the WBRT arm (n = 48). However, there were imbalances in the percentages of patients receiving previous chemotherapy and with synchronous brain metastases. Adding temozolomide to WBRT increased the frequency of nausea, vomiting, alopecia, fatigue, anorexia, and constipation. Most adverse events were mild to moderate. Conclusion: The benefit of adding temozolomide to WBRT was not confirmed; however, the accrual goal for the planned phase III trial was not reached, and the study regimen differed from regimens used previously. Therefore, the role of temozolomide in treating brain metastases remains unresolved.