CHRONOTHERAPY IN PERSONALIZED CANCER TREATMENT: CLINICAL EVIDENCE AND FUTURE DIRECTIONS

Madhurya Arkatala*, Shivani Kaduru

ABSTRACT

This narrative review is concerned with the clinical impact of chronotherapy, the timing of cancer treatment based on the natural 24-hour circadian clock of the body, on efficacy, toxicity, and overall outcome in adult patients with solid tumors. The circadian clock regulates cellular processes such as drug metabolism, DNA repair, and apoptosis, which can be disturbed by cancer. Accumulating evidence suggests that chronotherapy can enhance treatment efficacy while reducing treatment-related toxicity. Chronomodulated chemotherapy has been shown to improve progression-free survival (PFS) and reduces toxicity. Several observational studies have reported improved survival outcomes when immunotherapy is administered earlier in the day. Morning radiotherapy has also been associated with reduced toxicity, such as oral mucositis in head and neck cancer. However, the field faces major challenges, such as a lack of standardized circadian measures, the absence of large-scale multicenter trials, and irregular recording of precise treatment time. Future efforts should prioritize the integration of wearable technologies and precise treatment-time documentation to support individualized circadian-based therapy. The shift of population-averaged schedules to patient-specific chronotherapy can be used to address the existing limitations and enhance clinical outcomes.

Keywords: Chronotherapy; Circadian rhythm; Cancer treatment timing; Radiation oncology; Immunotherapy; Radiotherapy.