The efficacy of temozolomide for recurrent glioblastoma multiforme

Background and purpose: The efficacy of temozolomide (TMZ) in recurrent glioblastoma multiforme (GBM) has been evaluated by several clinical trials. A meta-analysis to assess the overall efficacy of TMZ in the treatment of recurrent GBM was carried out by the authors. Methods: Medline, EMBASE database and the Cochrane Library were searched for relevant studies. Eligible studies were clinical trials of recurrent GBMs assigned to TMZ with data on efficacy including tumor response, progression-free survival (PFS) or overall survival (OS) available. The overall efficacy was calculated using a random-effects or fixed-effects model, depending on the heterogeneity of the included trials. Results: A total of 15 phase II clinical trials including 902 recurrent GBMs were analyzed. The overall clinical benefit rate was 50.5% (95% CI: 44.3-56.7%) with significant difference between metronomic and standard schedules of TMZ (61.4% vs. 46.3%, P = 0.037). The overall 6-month PFS (PFS-6) rate was found to be 27.8% (95% CI: 22.7-33.5%) with significant difference between metronomic and standard schedules (33.1% vs. 20.1%, P < 0.001). In addition, significant difference in PFS-6 was detected between high (average daily dose >100 mg/m²) and low (average daily dose ≤100 mg/m²) dose metronomic schedules (RR = 1.57, 95% CI: 1.17-2.09, P = 0.002). The overall 6-month OS (OS-6) and 12-month OS (OS-12) rates were 65.0% (95% CI: 57.4-71.9%) and 36.4% (95% CI: 26.9-47.1%) separately. There was no significant difference in OS-6 between metronomic and standard schedules (P = 0.266); however, a trend was noted favoring the metronomic schedule for OS-12 (P = 0.089). Conclusions: Temozolomide is effective for recurrent GBMs, and its efficacy may be increased with metronomic schedule and high average daily dose (>100 mg/m²).