Preliminary data show survival benefit of morning temozolomide for glioblastoma
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Morning administration of temozolomide appeared associated with longer OS compared with evening administration among patients with newly diagnosed glioblastoma, according to study results published in Neuro-Oncology Advances.
The OS benefit appeared more pronounced among patients with methylated MGMT, researchers found.
“We conducted this study because the efficacy of temozolomide likely relates primarily to daily rhythms in DNA repair within the tumor. In addition, previous findings have shown improved survival when temozolomide was administered in the morning in a glioblastoma mouse model,” Jian L. Campian, MD, PhD, associate professor of medicine and neurological surgery and clinical director of the neuro-oncology program in the division of oncology at Washington University School of Medicine in St. Louis, told Healio.
Campian and colleagues conducted a retrospective study to assess the effect of maintenance temozolomide chronotherapy — the timed delivery of anticancer treatments according to patient daily rhythms — on OS among 166 patients (median age, 60.1 years; 96.39% white; 63.25% men) with newly diagnosed glioblastoma between 2010 and 2018.
All patients underwent surgery and chemoradiation and were prescribed temozolomide either in the morning (n = 89) or evening (n = 77). Researchers assessed OS using the Kaplan-Meier method and Cox regression model.
OS, calculated as the time interval from initiation of maintenance temozolomide until death or date of last contact with the patient, served as the primary outcome.
Median follow-up was 5.07 years.
Overall, 145 patients died within the study period. Median OS was 1.43 years (95% CI, 1.12-1.92) with morning temozolomide compared with 1.13 years (95% CI, 0.84-1.58) with evening temozolomide, and researchers reported a significant 1-year difference in restricted mean survival time of 0.09 (95% CI, 0.16 to 0.018).
Researchers also found that median OS was 6 months longer with morning vs. evening temozolomide (2.13 years vs. 1.63 years) among 56 patients with MGMT-methylated tumors, for a significant 1-year difference in restricted mean survival time of 0.13 (95% CI, 0.24 to approximately 0.019) and a 2.5-year difference of 0.43 (95% CI, 0.84 to approximately 0.028).
Moreover, the superiority of morning administration of temozolomide at years 1, 2 and 5 (P < .05 for all) for all patients was supported by restricted mean survival time difference regression following adjustment for confounders, the researchers noted.
“Our research shows that chemotherapy administered at different times may result in different outcomes, and the time of drug administration matters,” Campian said. “We are currently conducting a clinical trial to test temozolomide in the morning compared with evening administration.”
For more information:
Jian L. Campian, MD, PhD, can be reached at Washington University School of Medicine in St. Louis, 660 S. Euclid Ave., Campus Box 8056, St. Louis, MO 63110; email: campian.jian@wustl.edu.
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