The Royal Marsden Hospital NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK.
J Neurooncol. 2011 Nov;105(2):135-47. doi: 10.1007/s11060-011-0657-7. Epub 2011 Jul 5.
Low grade gliomas (LGG) contribute to 50% of all central nervous tumors in children and 15% of all gliomas in adults. Temozolomide (TMZ) is an oral alkylating agent with activity in high and LGG. Various regimens of TMZ are currently in use. We attempted to assess the impact of different TMZ regimens on the treatment of LGG. A systematic review of the literature identified all the studies published in Pubmed, EMBASE and Cochrane databases which met the inclusion criteria. The primary outcome measure was the impact of different TMZ regimens on the 12 month progression-free survival (PFS) rates of patients diagnosed with progressive LGG. Secondary outcome measures looked at the ability of the three regimens to elicit an objective response and the associated toxicity. Statistical pooling and calculation of weighted mean average of each proportion (WMAP) was conducted using a random-effects model. 18 studies (736 patients) were analyzed. PFS at 12 months revealed a WMAP of 0.61 (95% CI 0.44-0.78) for regimen A, 0.59 (0.28-0.89) for regimen B, and 0.91 (95% CI 0.83-0.99) for regimen C (Regimen A--200 mg/m(2)/day for 5 days, repeated every 4 weeks; B--75 mg/m(2)/day for 21 days repeated every 4 weeks; C--75 mg/m(2)/day for 7 weeks with 4 weeks of every 11 weeks). In terms of objective response, WMAP were 0.19 (95% 0.13-0.25), 0.27 (95% CI 0.15-0.39) and 0.21 (95% CI 0.10-0.32) for regimen A, B, C respectively. When analyzing hematological toxicity, WMAPs were 0.14 (95% 0.11-0.18), 0.35 (0.14-0.56) and 0.23 (95% CI 0.03-0.43). The bulk of evidence originates from the standard 5 day/month regimen A but with a lack of comparative studies. Analysis revealed significant heterogeneity. Although there is possibly an indication that metronomic regimens of TMZ result in better PFS and response rate when compared to the conventional standard 5 day regimen, insufficient available data and study heterogeneity preclude any safe conclusions. Well designed randomized controlled clinical trials are needed to establish the efficacy of metronomic regimens of TMZ in LGGs.
低级别胶质瘤（LGG）占儿童中枢神经系统肿瘤的 50%，占成人胶质瘤的 15%。替莫唑胺（TMZ）是一种口服烷化剂，对高级别和 LGG 均有活性。目前有多种 TMZ 方案在使用。我们试图评估不同 TMZ 方案对 LGG 治疗的影响。系统文献复习在 Pubmed、EMBASE 和 Cochrane 数据库中检索符合纳入标准的所有研究。主要结局指标是不同 TMZ 方案对诊断为进展性 LGG 患者 12 个月无进展生存率（PFS）的影响。次要结局指标是三种方案诱导客观反应的能力及其相关毒性。使用随机效应模型对每一项比例的加权平均值（WMAP）进行统计合并和计算。共分析了 18 项研究（736 例患者）。12 个月时的 PFS 显示，方案 A 的 WMAP 为 0.61（95%CI 0.44-0.78），方案 B 为 0.59（0.28-0.89），方案 C 为 0.91（95%CI 0.83-0.99）（方案 A-每天 200mg/m2，连用 5 天，每 4 周重复一次；B-每天 75mg/m2，连用 21 天，每 4 周重复一次；C-每周 75mg/m2，连用 7 周，每 11 周休息 4 周）。在客观反应方面，方案 A、B、C 的 WMAP 分别为 0.19（95%CI 0.13-0.25）、0.27（95%CI 0.15-0.39）和 0.21（95%CI 0.10-0.32）。分析血液学毒性时，WMAPs 分别为 0.14（95%CI 0.11-0.18）、0.35（0.14-0.56）和 0.23（95%CI 0.03-0.43）。大部分证据来自标准的 5 天/月方案 A，但缺乏对照研究。分析显示存在显著的异质性。尽管有迹象表明 TMZ 的节拍方案与传统的标准 5 天方案相比，能更好地提高 PFS 和反应率，但由于现有数据不足和研究异质性，无法得出任何安全结论。需要精心设计的随机对照临床试验来确定 TMZ 节拍方案在 LGG 中的疗效。
