Timing Cancer Treatment: A Simple Yet Effective Intervention Kenneth K. Lam/ZUMA Press/Alamy
The first randomized controlled trial investigating the timing of cancer immunotherapy has revealed that administering treatment earlier in the day may significantly enhance patient survival rates.
Human cells and tissues operate on a 24-hour cycle, known as the circadian rhythm, influencing various bodily functions including mood, metabolism, and immune response.
Numerous observational studies have indicated that cancer patients receiving checkpoint inhibitors (a class of immunotherapy drugs that empower the immune system to combat cancer) earlier in the day show a lower risk of disease progression and mortality.
Recently, Francis Levy and his team at the University of Paris-Saclay, France, conducted the first randomized controlled trial focused on chronotherapy—timing treatments based on circadian rhythms—utilizing both chemotherapy and immunotherapy.
In this study, 210 patients diagnosed with non-small cell lung cancer were given four doses of either pembrolizumab or sintilimab, two checkpoint inhibitors that function similarly.
Every three weeks, half of the participants received their doses before 3 p.m., while the others received treatments later. All patients also received chemotherapy immediately after each immunotherapy session. Chemotherapy targets rapidly dividing cells and is believed to have a lesser connection to circadian rhythms than immunotherapy.
This timing was strictly adhered to during the initial four cycles of the combined immunochemotherapy treatments. Following this period, all participants continued receiving the same medications until their tumors advanced or no longer responded, but without specific timing guidelines. Previous research suggests that the first four cycles are crucial, as noted by team member Zhang Yongchang from Central South University, China.
Participants were monitored for an average of 29 months post-initial treatment. Results showed that those treated before 3 p.m. had a median survival of 28 months, compared to 17 months for those treated later in the day. “The results are dramatically positive,” Levy stated. “Survival time nearly doubles.”
“When we compare our findings to significant trials that resulted in new drug approvals, such large effects are rarely observed,” noted Pasquale Innominato from the University of Warwick, UK. He emphasized that the study demonstrates a definitive link between treatment timing and survival outcomes, deeming it solid evidence of causation.
This dramatic improvement may be attributed to T cells, a type of immune cell targeted by checkpoint inhibitors, which tend to accumulate near tumors in the morning and gradually enter the bloodstream later. Administering immunotherapy earlier could position T cells closer to tumors, enabling more effective destruction, according to Levy.
Levy also emphasized the need for further studies to explore if more precise timing, such as 11 a.m., offers additional advantages compared to broader scheduled treatments. Innominato pointed out that having flexibility in timing is advantageous for busy healthcare facilities.
Further investigation is necessary to determine whether managing the timing of chemoimmunotherapy beyond the first four cycles yields greater benefits, Levy mentioned. Individual variability could also play a critical role; for example, a morning person may have different immune responses compared to a night owl.
Whether these findings apply to various cancer types remains an open question. Innominato anticipates similar results in other tumors commonly treated with immunotherapy, like skin or bladder cancers, but tempered his expectations for tumors such as prostate or pancreatic cancers that often resist treatments.
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Source: www.newscientist.com
