Department of Neuro-Oncology/Neurosurgery, Saitama Medical University International Medical Center, Saitama, Japan.
Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan.
Neuro Oncol. 2023 Apr 6;25(4):687-698. doi: 10.1093/neuonc/noac246.
The goal was to determine whether the addition of temozolomide (TMZ) to the standard treatment of high-dose methotrexate (HD-MTX) and whole-brain radiotherapy (WBRT) for primary central nervous system lymphoma (PCNSL) improves survival.
An open-label, randomized, phase III trial was conducted in Japan, enrolling immunocompetent patients aged 20-70 years with histologically confirmed, newly diagnosed PCNSL. After administration of HD-MTX, patients were randomly assigned to receive WBRT (30 Gy) ± 10 Gy boost (arm A) or WBRT ± boost with concomitant and maintenance TMZ for 2 years (arm B). The primary endpoint was overall survival (OS).
Between September 29, 2014 and October 15, 2018, 134 patients were enrolled, of whom 122 were randomly assigned and analyzed. At the planned interim analysis, 2-year OS was 86.8% (95% confidence interval [CI]: 72.5-94.0%) in arm A and 71.4% (56.0-82.2%) in arm B. The hazard ratio was 2.18 (95% CI: 0.95-4.98), with the predicted probability of showing the superiority of arm B at the final analysis estimated to be 1.3%. The study was terminated early due to futility. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was measured in 115 tumors, and it was neither prognostic nor predictive of TMZ response.
This study failed to demonstrate the benefit of concomitant and maintenance TMZ in newly diagnosed PCNSL.
本研究旨在确定替莫唑胺（TMZ）联合大剂量甲氨蝶呤（HD-MTX）和全脑放疗（WBRT）标准治疗方案是否能改善原发性中枢神经系统淋巴瘤（PCNSL）患者的生存。
本研究是在日本开展的一项开放性、随机、III 期临床试验，纳入了年龄在 20-70 岁之间、组织学确诊的新诊断为 PCNSL 的免疫功能正常的患者。在给予 HD-MTX 后，患者被随机分配接受 WBRT（30 Gy）±10 Gy 加量（A 组）或 WBRT±加量同时联合替莫唑胺辅助和维持治疗 2 年（B 组）。主要终点为总生存期（OS）。
2014 年 9 月 29 日至 2018 年 10 月 15 日期间共纳入 134 例患者，其中 122 例患者被随机分配并进行了分析。在计划的中期分析中，A 组 2 年 OS 率为 86.8%（95%置信区间[CI]：72.5-94.0%），B 组为 71.4%（56.0-82.2%）。风险比为 2.18（95%CI：0.95-4.98），最终分析时 B 组显示优越性的预测概率估计为 1.3%。由于无效，该研究提前终止。对 115 例肿瘤进行了 O6-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）启动子甲基化状态的检测，其既无预后价值也无预测替莫唑胺反应的价值。
本研究未能证明替莫唑胺联合治疗在新诊断的 PCNSL 中的获益。
