Korean researchers discovered that chemotherapy delivered in the afternoon for female patients with diffuse large B-cell lymphoma (DLBCL) can reduce toxicity and improve the efficacy of the treatment, according to a study published in JCI Insight. 

To this day, despite notable therapeutic advancements, cancer remains a leading cause of death globally. One of the key therapies for cancer today is chemotherapy, which usually consists of drug combinations administered to patients at a prescribed dose and frequency. 

While most research has focused on the type and quality of chemotherapy, there has been less research on the impact of delivery time on clinical outcomes. The authors of this study hence sought to explore the effects of implementing chronomodulated immunochemotherapy for patients with DLBCL. 

Read more about DLBCL etiology 

For most cases of DLBCL, the primary treatment option is rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone, a combination known as R-CHOP. Because it is the sole therapy used, researchers can be confident that confounding factors are negligible and that treatment outcomes are almost entirely dependent on how the treatment is administered, as well as its efficacy. 

In the research center at which this study was initiated, all chemotherapy treatments start at either 8:30 AM or 2:30 PM — a binary timing that helped researchers determine the relevance of chronotherapy, or specific timing of drug interventions, to clinical outcomes. 

There were 2 cohorts in this study: the “survival” cohort (n=210), consisting of patients who received 4 cycles of R-CHOP or more, and the “adverse events” cohort (n=129), consisting of patients who completed 6 cycles of R-CHOP and achieved complete remission. A control population of healthy individuals undergoing routine health checkups were recruited to provide data on normal diurnal variations in laboratory findings. 

Read more about R-CHOP

“Both progression-free survival and overall survival of female, but not male, patients were significantly shorter when patients received chemotherapy mostly in the morning,” the authors of the study wrote. “The sex-specific chronotherapeutic effects can be explained by the larger daily fluctuation of circulating leukocytes and neutrophils in females than in males.” 

This study suggests that there may be benefits in implementing sex-oriented chronotherapy as an alternative means of augmenting DLBCL frontline therapy. 


Kim DW, Byun JM, Lee JO, Kim JK, Koh Y. Chemotherapy delivery time affects treatment outcomes of female patients with diffuse large B-cell lymphomaJCI Insight. 2022;e164767. doi:10.1172/jci.insight.164767