Study: Chemotherapy to Treat Glioblastoma May Be More Effective During Morning

New research suggests that administering chemotherapy in the morning rather than in the evening could extend survival for patients with glioblastoma, adding a few months to their lives, according to investigators at Washington University School of Medicine.

Glioblastoma is an aggressive form of brain cancer with no cure. Patients survive an average of 15 months after diagnosis, with fewer than 10% of patients surviving longer than 5 years. Investigators are searching for potential new therapies with some ongoing clinical trials, but the minor adjustment to chemotherapy could make a significant difference.

In the study, the average overall survival (OS) for all patients was approximately 15 months after diagnosis. However, those receiving temozolomide in the morning had an average OS of approximately 17 months, compared to an average OS of approximately 13.5 months for those taking the drug in the evening. This 3.5-month difference is statistically significant, according to the study authors.

“We are working hard to develop better treatments for this deadly cancer, but even so, the best we can do right now is prolong survival and try to preserve quality of life for our patients,” said co-senior author and neuro-oncologist Jian L. Campian, MD, PhD, in the press release. “These results are exciting because they suggest we can extend survival simply by giving our standard chemotherapy in the morning.”

Earlier research has studied circadian rhythms and their effect on glioblastoma, finding that temozolomide was more effective when administered in the morning. Researcher Erik D. Herzog, PhD, said that although experts understand that astrocytes in the brain have natural daily rhythms, very few clinical trials consider time of day.

In a current study, investigators observed that improved survival with morning chemotherapy was more pronounced among a subset of patients with MGMT methylated tumors. Notably, patients with this tumor type tend to respond better to temozolomide in general, according to the study authors. For the 56 patients with MGMT methylated tumors, the average OS was approximately 25.5 months for those taking temozolomide in the morning and approximately 19.5 months for those taking it in the evening.

“The 6-month difference was quite impressive,” Campian said in the press release. “Temozolomide was approved to treat glioblastoma in 2005 based on a 10-week improvement in survival. So, any improvement in survival beyond 2 months is quite meaningful.”

In the new retrospective study, investigators analyzed data from 166 patients with glioblastoma who were treated between January 2010 and December 2018. All patients received the standard of care for glioblastoma, and they underwent surgery to remove as much of each tumor as possible and then received radiation therapy along with temozolomide. After the radiation and temozolomide regimen was complete, patients continued taking a maintenance dose of temozolomide either in the morning or the evening, depending on their oncologists’ preference.

“Until now, we have never considered that the timing of temozolomide might be important, so it’s up to the treating physician to advise the patient on when to take it,” Campian said in the press release. “Many oncologists give it in the evening because patients tend to report fewer side effects then. We saw that in our study as well. But it could be that the increased side effects—which we can manage with other therapies—are a sign that the drug is working more effectively.”

Campian noted that this was a relatively small retrospective analysis, and the team is conducting a clinical trial in which newly diagnosed glioblastoma patients are randomly assigned to receive temozolomide in either the morning or evening. Trials such as theirs will be essential to establish whether treatment timing can improve survival for glioblastoma patients, the study authors said.

“There have been no new drugs approved for glioblastoma in over a decade,” said researcher Jingqin Luo, PhD, in the press release. “That makes it necessary to think about other possible changes that make a drug more efficacious. Chemotherapy—or the timed delivery of drugs, based on circadian rhythms—is becoming a popular topic. It’s practical and realizable to implement chronotherapy to optimize existing drugs and treatments.”

REFERENCE

Chemo for glioblastoma may work better in morning than evening [news release]. Washington University School of Medicine in St. Louis; March 31, 2021. https://medicine.wustl.edu/news/chemo-for-glioblastoma-may-work-better-in-morning-than-evening/. Accessed April 5, 2021.