Temozolomide Chronotherapy in Glioma: A Systematic Review

Outcomes for patients with high-grade glioma remain poor. Temozolomide (TMZ) is the only drug approved for first-line treatment of glioblastoma multiforme, the most aggressive form of glioma. Chronotherapy highlights the potential benefit of timed TMZ administration. This is based on pre-clinical st...

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Main Authors: Jason L. Jia, Bader Alshamsan, Terry L. Ng
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:Current Oncology
Subjects:
Online Access:https://www.mdpi.com/1718-7729/30/2/147
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author Jason L. Jia
Bader Alshamsan
Terry L. Ng
author_facet Jason L. Jia
Bader Alshamsan
Terry L. Ng
author_sort Jason L. Jia
collection DOAJ
description Outcomes for patients with high-grade glioma remain poor. Temozolomide (TMZ) is the only drug approved for first-line treatment of glioblastoma multiforme, the most aggressive form of glioma. Chronotherapy highlights the potential benefit of timed TMZ administration. This is based on pre-clinical studies of enhanced TMZ-induced glioma cytotoxicity dependent on circadian, oscillating expression of key genes involved in apoptosis, DNA damage repair, and cell-cycle mediated cell death. The current systematic review’s primary aim was to evaluate the efficacy and toxicity of TMZ chronotherapy. A systemic review of literature following PRISMA guidelines looking at clinical outcomes on TMZ chronotherapy on gliomas was performed. The search in the English language included three databases (PubMed, EMBASE, and Cochrane) and five conferences from 1946 to April 2022. Two independent reviewers undertook screening, data extraction, and risk-of-bias assessment. A descriptive analysis was conducted due to limited data. Of the 269 articles screened, two unique studies were eligible and underwent abstraction for survival and toxicity findings. Both studies—one a retrospective cohort study (n = 166) and the other a prospective randomized feasibility study (n = 35)—were conducted by the same academic group and suggested a trend for improved overall survival, but possibly increased toxicity when TMZ was administered in the morning (vs. evening). There was limited evidence suggesting possible therapeutic value from administering TMZ in the morning, which may be consistent with the pre-clinical observations of the importance of the timing of TMZ administration in vitro. Larger, pragmatic, prospective randomized controlled trials are needed to ascertain the value of TMZ chronotherapy to provide optimized and equitable care for this population.
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spelling doaj.art-8d2d2c48294f4e609836c789fdd05e582023-11-16T19:57:58ZengMDPI AGCurrent Oncology1198-00521718-77292023-02-013021893190210.3390/curroncol30020147Temozolomide Chronotherapy in Glioma: A Systematic ReviewJason L. Jia0Bader Alshamsan1Terry L. Ng2Core Internal Medicine Residency Program, Department of Medicine, University of Ottawa, Ottawa, ON K1H 8L6, CanadaDepartment of Medicine, College of Medicine, Qassim University, Buraydah P.O. Box 6655, Saudi ArabiaDivision of Medical Oncology, Department of Medicine, The Ottawa Hospital Cancer Centre, Ottawa, ON K1H 8L6, CanadaOutcomes for patients with high-grade glioma remain poor. Temozolomide (TMZ) is the only drug approved for first-line treatment of glioblastoma multiforme, the most aggressive form of glioma. Chronotherapy highlights the potential benefit of timed TMZ administration. This is based on pre-clinical studies of enhanced TMZ-induced glioma cytotoxicity dependent on circadian, oscillating expression of key genes involved in apoptosis, DNA damage repair, and cell-cycle mediated cell death. The current systematic review’s primary aim was to evaluate the efficacy and toxicity of TMZ chronotherapy. A systemic review of literature following PRISMA guidelines looking at clinical outcomes on TMZ chronotherapy on gliomas was performed. The search in the English language included three databases (PubMed, EMBASE, and Cochrane) and five conferences from 1946 to April 2022. Two independent reviewers undertook screening, data extraction, and risk-of-bias assessment. A descriptive analysis was conducted due to limited data. Of the 269 articles screened, two unique studies were eligible and underwent abstraction for survival and toxicity findings. Both studies—one a retrospective cohort study (n = 166) and the other a prospective randomized feasibility study (n = 35)—were conducted by the same academic group and suggested a trend for improved overall survival, but possibly increased toxicity when TMZ was administered in the morning (vs. evening). There was limited evidence suggesting possible therapeutic value from administering TMZ in the morning, which may be consistent with the pre-clinical observations of the importance of the timing of TMZ administration in vitro. Larger, pragmatic, prospective randomized controlled trials are needed to ascertain the value of TMZ chronotherapy to provide optimized and equitable care for this population.https://www.mdpi.com/1718-7729/30/2/147chronotherapytemozolomidegliomaglioblastomachemotherapyoncology
spellingShingle Jason L. Jia
Bader Alshamsan
Terry L. Ng
Temozolomide Chronotherapy in Glioma: A Systematic Review
Current Oncology
chronotherapy
temozolomide
glioma
glioblastoma
chemotherapy
oncology
title Temozolomide Chronotherapy in Glioma: A Systematic Review
title_full Temozolomide Chronotherapy in Glioma: A Systematic Review
title_fullStr Temozolomide Chronotherapy in Glioma: A Systematic Review
title_full_unstemmed Temozolomide Chronotherapy in Glioma: A Systematic Review
title_short Temozolomide Chronotherapy in Glioma: A Systematic Review
title_sort temozolomide chronotherapy in glioma a systematic review
topic chronotherapy
temozolomide
glioma
glioblastoma
chemotherapy
oncology
url https://www.mdpi.com/1718-7729/30/2/147
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AT terrylng temozolomidechronotherapyingliomaasystematicreview