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

Research output: Contribution to journalReview article

26 Citations (Scopus)

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/m 2/day for 5 days, repeated every 4 weeks; B-75 mg/m 2/day for 21 days repeated every 4 weeks; C-75 mg/m 2/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.

Original languageEnglish
Pages (from-to)135-147
Number of pages13
JournalJournal of Neuro-Oncology
Volume105
Issue number2
DOIs
Publication statusPublished - 01-11-2011

Fingerprint

temozolomide
Glioma
Appointments and Schedules
Disease-Free Survival
Survival Rate
Outcome Assessment (Health Care)
Alkylating Agents
PubMed
Randomized Controlled Trials
Databases

All Science Journal Classification (ASJC) codes

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Cite this

Lashkari, Harsha Prasada ; Saso, Srdjan ; Moreno, Lucas ; Athanasiou, Thanos ; Zacharoulis, Stergios. / Using different schedules of Temozolomide to treat low grade gliomas : Systematic review of their efficacy and toxicity. In: Journal of Neuro-Oncology. 2011 ; Vol. 105, No. 2. pp. 135-147.
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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/m 2/day for 5 days, repeated every 4 weeks; B-75 mg/m 2/day for 21 days repeated every 4 weeks; C-75 mg/m 2/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.",
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Using different schedules of Temozolomide to treat low grade gliomas : Systematic review of their efficacy and toxicity. / Lashkari, Harsha Prasada; Saso, Srdjan; Moreno, Lucas; Athanasiou, Thanos; Zacharoulis, Stergios.

In: Journal of Neuro-Oncology, Vol. 105, No. 2, 01.11.2011, p. 135-147.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Using different schedules of Temozolomide to treat low grade gliomas

T2 - Systematic review of their efficacy and toxicity

AU - Lashkari, Harsha Prasada

AU - Saso, Srdjan

AU - Moreno, Lucas

AU - Athanasiou, Thanos

AU - Zacharoulis, Stergios

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AB - 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/m 2/day for 5 days, repeated every 4 weeks; B-75 mg/m 2/day for 21 days repeated every 4 weeks; C-75 mg/m 2/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.

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