The efficacy of temozolomide for recurrent glioblastoma multiforme.
OBJECTIVE
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/m(2) ) and low (average daily dose ≤ 100 mg/m(2) ) 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/m(2) ).
Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Chao
C
Chen
Tao
T
Xu
Yicheng
Y
Lu
Juxiang
J
Chen
Shenhong
S
Wu
D059250:Administration, Metronomic; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000517:prevention & control; D017322:Clinical Trials, Phase II as Topic; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005909:Glioblastoma / Q000188:drug therapy* / Q000517:prevention & control; D006801:Humans; D055502:Secondary Prevention; D015996:Survival Rate; D000077204:Temozolomide
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide