Gupta Tejpal, Talukdar Riddhijyoti, Kannan Sadhana, Dasgupta Archya, Chatterjee Abhishek, Patil Vijay
Department of Radiation Oncology, ACTREC/TMH, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, India.
Department of Clinical Research Secretariat, ACTREC/TMH, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, India.
Neurooncol Pract. 2022 May 7;9(5):354-363. doi: 10.1093/nop/npac036. eCollection 2022 Oct.
This study was designed to compare outcomes of extended adjuvant temozolomide (TMZ) vs standard adjuvant TMZ following radiotherapy (RT) plus concurrent TMZ in newly diagnosed glioblastoma.
This systematic review and meta-analysis was carried out in accordance with Cochrane methodology. Only prospective clinical trials randomly assigning adults with newly diagnosed glioblastoma after concurrent RT/TMZ to 6 cycles of adjuvant TMZ (control arm) or extended (>6 cycles) adjuvant TMZ (experimental arm) were eligible. Primary outcome of interest was overall survival, while progression-free survival and toxicity were secondary endpoints. Hazard ratio (HR) for progression and death with corresponding 95% confidence interval (CI) were computed for individual primary study and pooled using random-effects model. Toxicity was defined as proportion of patients with ≥grade 3 hematologic toxicity and expressed as risk ratio (RR) with 95% CI. Any -value <.05 was considered statistically significant.
Systematic literature review identified five randomized controlled trials comparing standard (6 cycles) vs extended (>6 cycles) adjuvant TMZ in newly diagnosed glioblastoma. Outcome data could be extracted from 358 patients from four primary studies. Extended adjuvant TMZ was not associated with statistically significant reduction in the risk of progression (HR = 0.82, 95% CI: 0.61-1.10; = .18) or death (HR = 0.87, 95% CI:0.60-1.27; = .48) compared to standard adjuvant TMZ. Grade ≥3 hematologic toxicity though somewhat higher with extended adjuvant TMZ, was not significantly different between the two arms (RR = 2.01, 95% CI: 0.83-4.87; = .12).
There is low-certainty evidence that extended adjuvant TMZ is not associated with significant survival benefit or increased hematologic toxicity in unselected patients with newly diagnosed glioblastoma compared to standard adjuvant TMZ.
本研究旨在比较新诊断的胶质母细胞瘤患者在放疗（RT）加同步替莫唑胺（TMZ）后，延长辅助替莫唑胺（TMZ）与标准辅助TMZ的疗效。
本系统评价和荟萃分析按照Cochrane方法进行。只有将新诊断的胶质母细胞瘤成年患者在同步放化疗后随机分为6周期辅助TMZ（对照组）或延长（>6周期）辅助TMZ（试验组）的前瞻性临床试验符合条件。主要关注结局为总生存期，无进展生存期和毒性为次要终点。计算各单项主要研究的进展和死亡风险比（HR）及相应的95%置信区间（CI），并使用随机效应模型进行汇总。毒性定义为≥3级血液学毒性患者的比例，以风险比（RR）及95%CI表示。任何P值<.05被认为具有统计学意义。
系统文献回顾确定了五项随机对照试验，比较新诊断的胶质母细胞瘤患者标准（6周期）与延长（>6周期）辅助TMZ的疗效。四项主要研究中358例患者的结局数据可提取。与标准辅助TMZ相比，延长辅助TMZ在进展风险（HR = 0.82，95%CI：0.61 - 1.10；P = 0.18）或死亡风险（HR = 0.87，95%CI：0.60 - 1.27；P = 0.48）方面无统计学显著降低。≥3级血液学毒性虽然延长辅助TMZ略高，但两组之间无显著差异（RR = 2.01，95%CI：0.83 - 4.87；P = 0.12）。
有低确定性证据表明，与标准辅助TMZ相比，延长辅助TMZ在未选择的新诊断胶质母细胞瘤患者中未显示出显著的生存获益或血液学毒性增加。
