Spiegel Brennan M R, Esrailian Eric, Laine Loren, Chamberlain Marc C
VA Greater Los Angeles Healthcare System, Los Angeles, California 90073, USA.
CNS Drugs. 2007;21(9):775-87. doi: 10.2165/00023210-200721090-00006.
A meta-analysis of chemotherapy for glioblastoma multiforme (GBM) was performed. We sought to update prior analyses by focusing exclusively on GBM, including new trials of novel treatments, assessing effectiveness of individual treatment categories and presenting data in a clinically useful format.
A search of MEDLINE and EMBASE was conducted for randomised controlled trials of chemotherapy in GBM.
Relative risks (RRs) for survival in 16 trials comparing chemotherapy with no chemotherapy were 1.18 (95% CI 1.08, 1.30) at 6 months, 1.53 (95% CI 1.26, 1.86) at 12 months and 2.12 (95% CI 1.60, 2.80) at 24 months. Nitrosourea compounds, local therapy (e.g. carmustine [1,3-bis [2-chloroethyl]-1-nitrosourea] wafers) and temozolomide were all more effective than no chemotherapy. Absolute increases in survival at 6, 12 and 24 months were 11%, 8% and 1%, respectively, for nitrosourea compounds; 8%, 24% and 5%, respectively, for local therapy; and 4%, 15% and 17%, respectively, for temozolomide. Efficacy of local therapy and temozolomide peaked at 12 and 18 months, respectively. After 2 years, nitrosourea compounds no longer provided clinically relevant benefit (number needed-to-treat [NNT] = 100; effect size [ES] = 0.17 SD), local therapy had diminishing returns (NNT = 20) that remained clinically relevant (ES = 0.71 SD) and temozolomide continued to show good efficacy (NNT = 5.9; ES = 0.74 SD). Survival was not significantly improved with multi-agent versus single-agent nitrosourea-based therapy in five trials: 6-month RR 0.91 (95% CI 0.71, 1.16); 24-month RR 1.33 (95% CI 0.72, 2.46).
Although nitrosourea compounds, local therapy and temozolomide are all effective in the treatment of GBM, local therapy and temozolomide may be associated with greater response, with clinically significant benefits extending to 24 months. The timing of peak benefits of local and temozolomide therapy suggests this combination may be more effective than single-agent chemotherapy and warrants further study.
对多形性胶质母细胞瘤（GBM）的化疗进行了一项荟萃分析。我们试图通过专门关注GBM来更新先前的分析，包括新的新型治疗试验，评估各个治疗类别的有效性，并以临床有用的格式呈现数据。
对MEDLINE和EMBASE进行检索，以查找GBM化疗的随机对照试验。
16项比较化疗与不化疗的试验中，6个月时生存的相对风险（RRs）为1.18（95%可信区间1.08，1.30），12个月时为1.53（95%可信区间1.26，1.86），24个月时为2.12（95%可信区间1.60，2.80）。亚硝基脲类化合物、局部治疗（如卡莫司汀[1,3-双[2-氯乙基]-1-亚硝基脲]晶片）和替莫唑胺都比不化疗更有效。亚硝基脲类化合物在6、12和24个月时生存的绝对增加分别为11%、8%和1%；局部治疗分别为8%、24%和5%；替莫唑胺分别为4%、15%和17%。局部治疗和替莫唑胺的疗效分别在12个月和18个月时达到峰值。2年后，亚硝基脲类化合物不再提供临床相关益处（需治疗人数[NNT]=100；效应大小[ES]=0.17标准差），局部治疗的收益递减（NNT=20），但仍具有临床相关性（ES=0.71标准差），替莫唑胺继续显示出良好疗效（NNT=5.9；ES=0.74标准差）。在五项试验中，基于亚硝基脲的多药治疗与单药治疗相比，生存并未显著改善：6个月RR为0.91（95%可信区间0.71，1.16）；24个月RR为1.33（95%可信区间0.72，2.46）。
尽管亚硝基脲类化合物、局部治疗和替莫唑胺在治疗GBM方面均有效，但局部治疗和替莫唑胺可能具有更大的反应，临床显著益处可延伸至24个月。局部治疗和替莫唑胺治疗的峰值益处时间表明，这种联合治疗可能比单药化疗更有效，值得进一步研究。
