Phase I and II Study of Induction Chemotherapy With Methotrexate, Rituximab, and Temozolomide, Followed By Whole-Brain Radiotherapy and Postirradiation Temozolomide for Primary CNS Lymphoma: NRG Oncology RTOG 0227
Phase I and II Study of Induction Chemotherapy With Methotrexate, Rituximab, and Temozolomide, Followed By Whole-Brain Radiotherapy and Postirradiation Temozolomide for Primary CNS Lymphoma: NRG Oncology RTOG 0227
复制标题
DOI：
10.1200/jco.2015.64.8634
复制
发表时间：
2016-05-10
影响因子：
45.3
通讯作者：
Mehta, Minesh P.
中科院分区：
文献类型：
--
作者：
Glass, Jon;Won, Minhee;Mehta, Minesh P.
目的本研究探讨了甲氨蝶呤、替莫唑胺（TMZ）和利妥昔单抗治疗原发性CNS淋巴瘤，然后进行超分割全脑放疗（hWBRT）和随后的TMZ。主要的I期终点是TMZ的最大耐受剂量。主要的II期终点是2年总生存率（OS）。次要终点是放疗前反应率、无进展生存期（PFS）、神经毒性和生活质量。患者和方法I期研究将TMZ剂量从100 mg/m2增加到150 mg/m2至200 mg/m2。患者在第1周期前3天接受利妥昔单抗375 mg/m2治疗;在第1、3、5、7和9周接受甲氨蝶呤3.5 g/m2联合甲酰四氢叶酸治疗;在第4和8周接受TMZ每日一次治疗，共5天;在第11至13周接受hWBRT 1.2戈伊每日两次治疗（36戈伊）; TMZ 200 mg/m2，每日1次，每28天1次，共5天，疗程14 ~ 50周。TMZ的最大耐受剂量为100 mg/m2。剂量限制性毒性为肝脏和肾脏。在第二阶段，53名患者接受了治疗。符合条件的存活患者的中位随访时间为3.6年，2年OS和PFS分别为80.8%和63.6%。与RTOG-9310的历史对照相比，2年OS和PFS显著改善（分别为P = 0.006和0.030）。在II期，客观缓解率为85.7%。在患者中，66%（53例中的35例）在hWBRT前发生了3级和4级毒性，45%（53例中的24例）的患者发生了可归因于hWBRT后化疗的3级和4级毒性。hWBRT.ConclusionThis方案是安全的，最好的2年OS和PFS实现在任何放射治疗肿瘤组原发性CNS淋巴瘤试验的认知功能和生活质量的改善或稳定。需要进行纳入该方案的随机试验，以确定其与其他策略相比的疗效。(C)2016年美国临床肿瘤学会
PurposeThis study investigated the treatment of primary CNS lymphoma with methotrexate, temozolomide (TMZ), and rituximab, followed by hyperfractionated whole-brain radiotherapy (hWBRT) and subsequent TMZ. The primary phase I end point was the maximum tolerated dose of TMZ. The primary phase II end point was the 2-year overall survival (OS) rate. Secondary end points were preirradiation response rates, progression-free survival (PFS), neurologic toxicities, and quality of life.Patients and MethodsThe phase I study increased TMZ doses from 100 to 150 to 200 mg/m(2). Patients were treated with rituximab 375 mg/m(2) 3 days before cycle 1; methotrexate 3.5 g/m(2) with leucovorin on weeks 1, 3, 5, 7, and 9; TMZ daily for 5 days on weeks 4 and 8; hWBRT 1.2 Gy twice-daily on weeks 11 to 13 (36 Gy); and TMZ 200 mg/m(2) daily for 5 days every 28 days on weeks 14 to 50.ResultsThirteen patients (one ineligible) were enrolled in phase I of the study. The maximum tolerated dose of TMZ was 100 mg/m(2). Dose-limiting toxicities were hepatic and renal. In phase II, 53 patients were treated. Median follow-up for living eligible patients was 3.6 years, and 2-year OS and PFS were 80.8% and 63.6%, respectively. Compared with historical controls from RTOG-9310, 2-year OS and PFS were significantly improved (P = .006 and .030, respectively). In phase II, the objective response rate was 85.7%. Among patients, 66% (35 of 53) had grade 3 and 4 toxicities before hWBRT, and 45% (24 of 53) of patients experienced grade 3 and 4 toxicities attributable to post-hWBRT chemotherapy. Cognitive function and quality of life improved or stabilized after hWBRT.ConclusionThis regimen is safe, with the best 2-year OS and PFS achieved in any Radiation Therapy Oncology Group primary CNS lymphoma trial. Randomized trials that incorporate this regimen are needed to determine its efficacy compared with other strategies. (C) 2016 by American Society of Clinical Oncology