Topic Review

Journal of Neuro-Oncology

, Volume 105, Issue 2, pp 135-147

First online:

Using different schedules of Temozolomide to treat low grade gliomas: systematic review of their efficacy and toxicity

  • Harsha Prasada LashkariAffiliated withThe Royal Marsden Hospital NHS Foundation Trust
  • , Srdjan SasoAffiliated withDivision of Surgery and Cancer, Institute of Reproductive & Developmental Biology, Imperial College London, Hammersmith Hospital Campus
  • , Lucas MorenoAffiliated withDrug Development, The Royal Marsden Hospital NHS Foundation Trust
  • , Thanos AthanasiouAffiliated withDepartment of Cardiothoracic Surgery, National Heart and Lung Institute, Imperial College London. The Hammersmith Hospital
  • , Stergios ZacharoulisAffiliated withChildren and Young People’s Unit, The Royal Marsden Hospital NHS Foundation Trust Email author 

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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/m2/day for 5 days, repeated every 4 weeks; B—75 mg/m2/day for 21 days repeated every 4 weeks; C—75 mg/m2/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.


Low grade gliomas (LGG) Children Temozolomide Metronomic chemotherapy