Cargando…

Temozolomide chronotherapy in patients with glioblastoma: a retrospective single-institute study

BACKGROUND: Chronotherapy is an innovative approach to improving survival through timed delivery of anti-cancer treatments according to patient daily rhythms. Temozolomide (TMZ) is a standard-of-care chemotherapeutic agent for glioblastoma (GBM). Whether timing of TMZ administration affects GBM pati...

Descripción completa

Detalles Bibliográficos
Autores principales: Damato, Anna R, Luo, Jingqin, Katumba, Ruth G N, Talcott, Grayson R, Rubin, Joshua B, Herzog, Erik D, Campian, Jian L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086242/
https://www.ncbi.nlm.nih.gov/pubmed/33959716
http://dx.doi.org/10.1093/noajnl/vdab041
_version_ 1783686483230588928
author Damato, Anna R
Luo, Jingqin
Katumba, Ruth G N
Talcott, Grayson R
Rubin, Joshua B
Herzog, Erik D
Campian, Jian L
author_facet Damato, Anna R
Luo, Jingqin
Katumba, Ruth G N
Talcott, Grayson R
Rubin, Joshua B
Herzog, Erik D
Campian, Jian L
author_sort Damato, Anna R
collection PubMed
description BACKGROUND: Chronotherapy is an innovative approach to improving survival through timed delivery of anti-cancer treatments according to patient daily rhythms. Temozolomide (TMZ) is a standard-of-care chemotherapeutic agent for glioblastoma (GBM). Whether timing of TMZ administration affects GBM patient outcome has not previously been studied. We sought to evaluate maintenance TMZ chronotherapy on GBM patient survival. METHODS: This retrospective study reviewed patients with newly diagnosed GBM from January 1, 2010 to December 31, 2018 at Washington University School of Medicine who had surgery, chemoradiation, and were prescribed TMZ to be taken in the morning or evening. The Kaplan–Meier method and Cox regression model were used for overall survival (OS) analyses. The propensity score method accounted for potential observational study biases. The restricted mean survival time (RMST) method was performed where the proportional hazard assumption was violated. RESULTS: We analyzed 166 eligible GBM patients with a median follow-up of 5.07 years. Patients taking morning TMZ exhibited longer OS compared to evening (median OS, 95% confidence interval [CI] = 1.43, 1.12–1.92 vs 1.13, 0.84–1.58 years) with a significant year 1 RMST difference (−0.09, 95% CI: −0.16 to −0.018). Among MGMT-methylated patients, median OS was 6 months longer for AM patients with significant RMST differences at years 1 (−0.13, 95% CI = −0.24 to −0.019) to 2.5 (−0.43, 95% CI = −0.84 to −0.028). Superiority of morning TMZ at years 1, 2, and 5 (all P < .05) among all patients was supported by RMST difference regression after adjusting for confounders. CONCLUSIONS: Our study presents preliminary evidence for the benefit of TMZ chronotherapy to GBM patient survival. This impact is more pronounced in MGMT-methylated patients.
format Online
Article
Text
id pubmed-8086242
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-80862422021-05-05 Temozolomide chronotherapy in patients with glioblastoma: a retrospective single-institute study Damato, Anna R Luo, Jingqin Katumba, Ruth G N Talcott, Grayson R Rubin, Joshua B Herzog, Erik D Campian, Jian L Neurooncol Adv Clinical Investigations BACKGROUND: Chronotherapy is an innovative approach to improving survival through timed delivery of anti-cancer treatments according to patient daily rhythms. Temozolomide (TMZ) is a standard-of-care chemotherapeutic agent for glioblastoma (GBM). Whether timing of TMZ administration affects GBM patient outcome has not previously been studied. We sought to evaluate maintenance TMZ chronotherapy on GBM patient survival. METHODS: This retrospective study reviewed patients with newly diagnosed GBM from January 1, 2010 to December 31, 2018 at Washington University School of Medicine who had surgery, chemoradiation, and were prescribed TMZ to be taken in the morning or evening. The Kaplan–Meier method and Cox regression model were used for overall survival (OS) analyses. The propensity score method accounted for potential observational study biases. The restricted mean survival time (RMST) method was performed where the proportional hazard assumption was violated. RESULTS: We analyzed 166 eligible GBM patients with a median follow-up of 5.07 years. Patients taking morning TMZ exhibited longer OS compared to evening (median OS, 95% confidence interval [CI] = 1.43, 1.12–1.92 vs 1.13, 0.84–1.58 years) with a significant year 1 RMST difference (−0.09, 95% CI: −0.16 to −0.018). Among MGMT-methylated patients, median OS was 6 months longer for AM patients with significant RMST differences at years 1 (−0.13, 95% CI = −0.24 to −0.019) to 2.5 (−0.43, 95% CI = −0.84 to −0.028). Superiority of morning TMZ at years 1, 2, and 5 (all P < .05) among all patients was supported by RMST difference regression after adjusting for confounders. CONCLUSIONS: Our study presents preliminary evidence for the benefit of TMZ chronotherapy to GBM patient survival. This impact is more pronounced in MGMT-methylated patients. Oxford University Press 2021-03-02 /pmc/articles/PMC8086242/ /pubmed/33959716 http://dx.doi.org/10.1093/noajnl/vdab041 Text en © The Author(s) 2021. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Clinical Investigations
Damato, Anna R
Luo, Jingqin
Katumba, Ruth G N
Talcott, Grayson R
Rubin, Joshua B
Herzog, Erik D
Campian, Jian L
Temozolomide chronotherapy in patients with glioblastoma: a retrospective single-institute study
title Temozolomide chronotherapy in patients with glioblastoma: a retrospective single-institute study
title_full Temozolomide chronotherapy in patients with glioblastoma: a retrospective single-institute study
title_fullStr Temozolomide chronotherapy in patients with glioblastoma: a retrospective single-institute study
title_full_unstemmed Temozolomide chronotherapy in patients with glioblastoma: a retrospective single-institute study
title_short Temozolomide chronotherapy in patients with glioblastoma: a retrospective single-institute study
title_sort temozolomide chronotherapy in patients with glioblastoma: a retrospective single-institute study
topic Clinical Investigations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086242/
https://www.ncbi.nlm.nih.gov/pubmed/33959716
http://dx.doi.org/10.1093/noajnl/vdab041
work_keys_str_mv AT damatoannar temozolomidechronotherapyinpatientswithglioblastomaaretrospectivesingleinstitutestudy
AT luojingqin temozolomidechronotherapyinpatientswithglioblastomaaretrospectivesingleinstitutestudy
AT katumbaruthgn temozolomidechronotherapyinpatientswithglioblastomaaretrospectivesingleinstitutestudy
AT talcottgraysonr temozolomidechronotherapyinpatientswithglioblastomaaretrospectivesingleinstitutestudy
AT rubinjoshuab temozolomidechronotherapyinpatientswithglioblastomaaretrospectivesingleinstitutestudy
AT herzogerikd temozolomidechronotherapyinpatientswithglioblastomaaretrospectivesingleinstitutestudy
AT campianjianl temozolomidechronotherapyinpatientswithglioblastomaaretrospectivesingleinstitutestudy