Journal of Neuro-Oncology

, 105:135 | Cite as

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

  • Harsha Prasada Lashkari
  • Srdjan Saso
  • Lucas Moreno
  • Thanos Athanasiou
  • Stergios Zacharoulis
Topic Review

Abstract

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.

Keywords

Low grade gliomas (LGG) Children Temozolomide Metronomic chemotherapy 

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Harsha Prasada Lashkari
    • 1
  • Srdjan Saso
    • 2
  • Lucas Moreno
    • 3
  • Thanos Athanasiou
    • 4
  • Stergios Zacharoulis
    • 5
  1. 1.The Royal Marsden Hospital NHS Foundation TrustSuttonUK
  2. 2.Division of Surgery and CancerInstitute of Reproductive & Developmental Biology, Imperial College London, Hammersmith Hospital CampusLondonUK
  3. 3.Drug DevelopmentThe Royal Marsden Hospital NHS Foundation TrustSuttonUK
  4. 4.Department of Cardiothoracic SurgeryNational Heart and Lung Institute, Imperial College London. The Hammersmith HospitalLondonUK
  5. 5.Children and Young People’s UnitThe Royal Marsden Hospital NHS Foundation TrustSuttonUK

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