Lead-in phase to randomized trial of motexafin gadolinium and whole-brain radiation for patients with brain metastases: Centralized assessment of magnetic resonance imaging, neurocognitive, and neurologic end points
Lead-in phase to randomized trial of motexafin gadolinium and whole-brain radiation for patients with brain metastases: Centralized assessment of magnetic resonance imaging, neurocognitive, and neurologic end points
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DOI：
10.1200/jco.2002.07.500
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发表时间：
2002-08-15
影响因子：
45.3
通讯作者：
Renschler, MF
中科院分区：
文献类型：
--
作者：
Mehta, MP;Shapiro, WR;Renschler, MF
目的：Motexafin gadolinium是一种氧化还原介体，选择性靶向肿瘤细胞，可通过磁共振成像（MRI）检测，并增强放射治疗的效果。该随机试验的导入期用于评估放射学、神经认知和神经学进展终点，并评估在10次全脑放射治疗中同时给予30戈伊的Motexafin gadolinium治疗脑转移瘤的安全性和放射学反应。在这项前瞻性国际试验中，在每次放射治疗前给予Motexafin godolinium（5.0 mg/kg/d，持续10天）。通过MRI、神经系统检查和神经认知测试对患者进行评估。前瞻性标准和集中审查程序建立了放射学，神经认知，神经系统进展endpoint.Results：25例脑转移肺癌（52%）和乳腺癌（24%），递归分区分析类2（96%），平均11个脑转移瘤患者入组。神经认知功能在就诊时高度受损。Motexafin钆的耐受性良好。1年时无神经系统进展率为77%。中位生存期为5.0个月。在29%的患者中，死亡原因是脑转移进展。放射学缓解率为68%。结论：（1）成功实施了结合神经认知测试的集中神经进展评分。(2)Motexafin钆的耐受性良好。(3)通过放射学缓解率、神经系统进展和脑转移进展导致的死亡来衡量局部控制，与历史结果相比似乎有所改善。一项使用这些方法评估疗效的随机III期试验刚刚完成。(C)2002年，美国临床肿瘤学会。
Purpose: Motexafin gadolinium is a redox mediator that selectively targets tumor cells, is detectable by magnetic resonance imaging (MRI), and enhances the effect of radiation therapy. This lead-in phase to a randomized trial served to evaluate radiologic, neurocognitive, and neurologic progression end points and to evaluate the safety and radiologic response of motexafin gadolinium administered concurrently with 30 Gy in 10-fraction whole-brain radiation therapy for the treatment of brain metastases.Patients and Methods: Motexafin godolinium (5.0 mg/kg/d for 10 days) was administered before each radiation treatment in this prospective international trial. Patients were evaluated by MRI, neurologic examinations, and neurocognitive tests. Prospective criteria and centralized review procedures were established for radiologic, neurocognitive, and neurologic progression end points.Results: Twenty-five patients with brain metastases from lung (52%) and breast (24%) cancer, recursive partitioning analysis class 2 (96%), and an average of 11 brain metastases were enrolled. Neurocognitive function was highly impaired at presentation. Motexafin gadolinium was well tolerated. Freedom from neurologic progression was 77% at 1 year. Median survival was 5.0 months. In 29% of patients, the cause of death was brain metastasis progression. The radiologic response rate was 68%. Motexafin gadolinium's tumor selectivity was established with MRI.Conclusion: (1) Centralized neurologic progression scoring that incorporated neurocognitive tests was implemented successfully. (2) Motexafin gadolinium was well tolerated. (3) Local control, measured by radiologic response rate, neurologic progression, and death caused by progression of brain metastasis, seemed to be improved compared with historical results. A randomized phase III trial using these methods for evaluation of efficacy has just been completed. (C) 2002 by American Society of Clinical Oncology.