Neuro-oncology practiceMar 20, 2025

Temozolomide chemotherapy for new glioblastoma patients: Does the timing of treatment affect outcomes?

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Mar 29, 2026

Abstract

In a cohort of 810 glioblastoma patients, 39% received temozolomide in the morning.

No significant difference in was observed between patients taking temozolomide in the morning and those taking it in the evening.
In the CENTRIC trial, the median overall survival was 20.6 months for morning administration and 21.1 months for evening administration.
In the CORE trial, the median overall survival was 10.9 months for morning administration and 11.4 months for evening administration.
Morning administration of temozolomide was associated with a higher incidence of compared to evening administration.
Bone marrow toxicity rates were 33% for morning versus 11% for evening in CENTRIC, and 24% for morning versus 3% for evening in CORE.

Simplified

BACKGROUND: Preclinical work and retrospective studies suggest that temozolomide chemotherapy in glioblastoma may be more effective when administered in the morning rather than the evening. Here we examine the effect of timing in a large cohort of patients in 2 contemporaneous randomized clinical trials.

METHODS: We assessed toxicity and survival data in patients with newly diagnosed glioblastoma enrolled in the CENTRIC EORTC 26071-22072 ( = 545, MGMT methylated) and CORE ( = 265, MGMT unmethylated) trials. We compared the outcome and toxicity of patients who took maintenance (adjuvant) temozolomide (TMZ) either in the morning (TMZ-m), afternoon (TMZ-a) or in the evening (TMZ-e). n n

RESULTS: In CENTRIC and CORE, = 102/260 (39%) and 50/198 (25%) received TMZ in the morning versus = 35/260 (13%) and 34/198 (17%) in the evening. There was no difference in (OS) between the TMZ-m and TMZ-e groups (CENTRIC: adjusted mOS 20.6 months (95% confidence interval [CI], 18.4-23.4) TMZ-m vs 21.1 months (95% CI, 18.4-24.5) TMZ-e; adjusted hazard ratio (HR), 0.93 (95% CI, 0.63-1.39); = .7; CORE: adjusted mOS, 10.9 months (95%CI, 9.7-11.8) TMZ-m vs 11.4 months (95%CI, 9.9-12.9) TMZ-e; adjusted HR, 0.87, 95%CI, 0.55-1.38); = .6). The TMZ-m group had a higher proportion of (CENTRIC: TMZ-m 33% vs TMZ-e 11%, = .013, CORE: TMZ-m 24% vs TMZ-e 3%, < .01). n n P P P P

CONCLUSION: In this post hoc analysis, we found no difference in outcome based on the time of TMZ administration. Bone marrow toxicity might occur more frequently when temozolomide is administered in the morning. Given the limitation to data from deceased patients only, these analyses should be viewed as exploratory only.

Key numbers

20.6 months

Median in CENTRIC

Adjusted median for morning vs. evening administration.

33%

Higher Rate

Proportion of patients with in CENTRIC.

5.3 months

Longer in CORE

Adjusted median for morning vs. evening administration in CORE.

Full Text

We can’t show the full text here under this license.

View Full Text ↗

Funding

Competing interests

MG: Grants or contracts from Evgen Pharm, Servier, LB: none, FK: none, BN: Patient care cost for the CORE clinical trial by MERC, consulting fees from AnHeart Scientific, Servier Advisory Board Advisory Board, Patent for SR42127 HuR dimerization inhibitor submitted, chair of Data safety monitoring board of CNS Pharma, DR: Consulting fees for AnHeart Pharmaceuticals; Aptitude Health; BlueRock Therapeutics LP; CeCaVaGmbH & Co.KG; Chimeric Therapeutics; Elsevier; F. Hoffman La-Roche; Genenta Science; Inovio; Insightec; Janssen; Jupiter Life Sciences Consulting, LLC; Kintara; Kiyatec; Johnson & Johnson, Pharma; Lumanity; Menari Stemline; MGH Healthcare Holdings; Miltenyi Biomedicine GmbH; Neuvogen; Novocure; Paradigm Medical Communications; Putnam Inizii Associates, LLC; Sumitono Dainippon Pharma; Oncology; Triangle Insights Group; UCLA; UCSF; U of Minnesota; Vivacitas Oncology, Inc.; WebMD. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events for AnHeart Pharmaceuticals; Aptitude Health; BlueRock Therapeutics LP; CeCaVaGmbH & Co.KG; Chimeric Therapeutics; Elsevier; F. Hoffman La-Roche; Genenta Science; Inovio; Insightec; Janssen; Jupiter Life Sciences Consulting, LLC; Kintara; Kiyatec; Johnson & Johnson, Pharma; Lumanity; Menari Stemline; MGH Healthcare Holdings; Miltenyi Biomedicine GmbH; Neuvogen; Novocure; Paradigm Medical Communications; Putnam Inizii Associates, LLC; Sumitono Dainippon Pharma; Oncology; Triangle Insights Group; UCLA; UCSF; U of Minnesota; Vivacitas Oncology, Inc.; WebMD. Participation on a Data Safety Monitoring Board or Advisory Board for ImVax; CeCaVaGmbH; University of Pennsylvania. Stock or stock options fro AnHeart Therapeutics; Bionaut Labs, JCT: Research grants from novocure and Munich Surgical Instruments, Royalties from Spinger Publisher, and Honorarium for consultation from Novartis, Support from servier for attending meetings, leadership role in WFNS, RS: none, TG: none, MW: Grants or contracts from Novartis, Versameb, Quercis; Participation on a Data Safety Monitoring Board or Advisory Board for Curevac, Orbus, Philogen, MP: Consulting fees from Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra, Gan & Lee Pharmaceuticals, Janssen, Servier, Miltenyi, Böhringer-Ingelheim, Telix, Medscape. MP has received honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, GLG, CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra, Gan & Lee Pharmaceuticals, Janssen, Servier, Miltenyi, Böhringer-Ingelheim, Telix, Medscape.

PubMed

Temozolomide chemotherapy for new glioblastoma patients: Does the timing of treatment affect outcomes?

Abstract

Key numbers

Full Text

Funding

Competing interests

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the circadian biology brief

Abstract

Key numbers

Full Text

Funding

Competing interests

Related papers

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the circadian biology brief