Phase 2 study of concurrent radiotherapy and temozolomide followed by temozolomide and lomustine in the treatment of children with high-grade glioma: a report of the Children's Oncology Group ACNS0423 study.
同期放疗和替莫唑胺后替莫唑胺和洛莫司汀治疗儿童高级别胶质瘤的 2 期研究: 儿童肿瘤组 ACNS0423 研究报告。
astrocytoma glioblastoma lomustine pediatric high-grade glioma temozolomide
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摘要

BACKGROUND:The prognosis for children with malignant glioma is poor. This study was designed to determine whether lomustine and temozolomide following radiotherapy and concurrent temozolomide improves event-free survival (EFS) compared with historical controls with anaplastic astrocytoma (AA) or glioblastoma (GBM) and whether survival is influenced by the expression of O6-methylguanine-DNA-methyltransferase (MGMT).
METHODS:Following maximal surgical resection, newly diagnosed children with nonmetastatic high-grade glioma underwent involved field radiotherapy with concurrent temozolomide. Adjuvant chemotherapy consisted of up to 6 cycles of lomustine 90 mg/m(2) on day 1 and temozolomide 160 mg/m(2)/day ×5 every 6 weeks.
RESULTS:Among the 108 eligible patients with AA or GBM, 1-year EFS was 0.49 (95% CI, 0.39-0.58), similar to the original CCG-945-based design model. However, EFS and OS were significantly improved in ACNS0423 compared with the 86 AA or GBM participants treated with adjuvant temozolomide alone in the recent ACNS0126 study (1-sided log-rank P = .019 and .019, respectively). For example, 3-year EFS was 0.22 (95% CI, 0.14-0.30) in ACNS0423 compared with 0.11 (95% CI, 0.05-0.18) in ACNS0126. Stratifying the comparison by resection extent, the addition of lomustine resulted in significantly better EFS and OS in participants without gross-total resection (P = .019 and .00085 respectively). The difference in EFS and OS was most pronounced for participants with GBM (P = .059 and 0.051, respectively), and those with MGMT overexpression (P = .00036 and .00038, respectively).
CONCLUSION:The addition of lomustine to temozolomide as adjuvant therapy in ACNS0423 was associated with significantly improved outcome compared with the preceding COG ACNS0126 HGG study in which participants received temozolomide alone.

译文

背景: 儿童恶性胶质瘤的预后较差。本研究旨在确定洛莫司汀和替莫唑胺在放射治疗后并发替莫唑胺是否能提高无事件生存率 (EFS),与历史对照相比,未分化星形细胞瘤 (AA) 或胶质母细胞瘤 (GBM) 以及生存是否受 O6-methylguanine-DNA-methyltransferase (MGMT) 表达的影响。
方法: 在最大限度的手术切除之后,新诊断的儿童非转移性高级别胶质瘤接受了介入野放射治疗,同时进行了替莫唑胺。辅助化疗包括 6 个周期的洛莫司汀 90 mg/m (2) 在第一天,替莫唑胺 160 mg/m (2)/天 × 5 每 6 周。
结果: 在 108 名符合条件的 AA 或 GBM 患者中,1 年 EFS 为 0.49 (95% CI,0.39-0.58),与原始 CCG-945-based 设计模型相似。然而,在最近的 ACNS0126 研究中,与单独使用替莫唑胺辅助治疗的 86 名 AA 或 GBM 参与者相比,ACNS0423 的 EFS 和 OS 显著改善 (1 面对数秩 P =。 019 和。 019,分别为)。例如,ACNS0423 的 3 年 EFS 为 0.22 (95% 置信区间,0.14-0.30),而 acns0126 为 0.11 (95% 置信区间,0.05-0.18)。根据切除程度对比较进行分层,在未进行完全切除的参与者中,洛莫司汀的添加显著改善了 EFS 和 OS (分别为 P =.019 和.00085)。GBM 参与者的 EFS 和 OS 差异最明显 (P =。 059 和 0.051),和 MGMT 过表达 (P =。 00036 和。 00038,分别)。
结论: 与之前的 COG ACNS0126 HGG 研究相比,在 ACNS0423 中添加洛莫司汀作为替莫唑胺的辅助治疗与显著改善的结果相关,在此研究中,参与者单独接受替莫唑胺。

Lomustine

肿瘤 DNA烷化剂 药物
概述  :  

洛莫司汀,是一种DNA烷化剂,具有抗肿瘤活性。通过在体内产生氯乙基碳离子和碳酰化中间体,这些亲电化合物攻击DNA上的亲核部位,形成烷基化产物,从而发挥药效作用的。其他类别的抗癌药物,比如丝裂霉素C、链霉素、博来霉素和蒽环类,需要生物激活作用来与细胞靶点反应,而洛莫司汀不需要预激活。不同于作用于鸟嘌呤的N7烷基化试剂,洛莫司汀则在O6形成氯乙基化加合物,进而导致链间DNA的交联。如果DNA不进行修复,这种交联会在DNA复制过程中导致双链断裂,最终细胞凋亡导致细胞死亡。洛莫司汀作为一种可口服抗肿

Lomustine 

释    义   n. 环己亚硝脲(抗癌药);罗氮芥;洛莫司汀; 洛莫司丁

例    句   Chest or mediastinal radiation, bleomycin, or carmustine or lomustine therapy should have baseline lung function testing, then every 3-5 years as needed. 胸部或纵隔的放射治疗,博来霉素、卡莫司汀或洛莫司汀的药物治疗应该伴随基本的肺功能检测,根据需要每3至5年检测一次。

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