Interruption of biological rhythms during chemotherapy worsens side effects

Chemotherapy disrupts circadian rhythms leading to a higher risk for clinically relevant fatigue or weight loss. This study, published in the International Journal of Cancer (doi:10.1002/ijc.28587), showed the importance of preventing chronodisruption and implementing measures to strengthen the circadian rhythms in patients undergoing chemotherapy.

The circadian system, also known as the biological clock or biological rhythm, regulates many physiological processes that occur in the human body. Disruption of circadian rhythm (chronodisruption), has been linked to an increased incidence of cancer, obesity, diabetes, depression, cognitive problems, and cardiovascular disease.

"Circadian disruption in cancer patients aggravates the disease process, decreasing the patient's chances for survival," said Elisabet Ortiz Tudela, MSc, a researcher at the Chronobiology Laboratory, Department of Physiology, University of Murcia, Spain.

Studying circadian rhythms in human beings is a challenge because the clock is located deep within the brain in the suprachiasmatic nucleus of the hypothalamus.

"It is impossible to directly assess how the clock works," said Ortiz Tudela. "Biological rhythms are studied by interrupting the clock, which enables us to study the status of the circadian system indirectly."

The activity-rest rhythm is one of the most studied interruptions and can be measured with non-invasive techniques over time.

Researchers characterized the circadian system in cancer patients submitted to a standard chronotherapy protocol (synchronization of medication with natural rhythms). The activity-rest rhythm was recorded in 49 patients with advanced cancer who received a standard chrono-modulated chemotherapy cycle that resulted in circadian disruption.

All of the parameters studied worsened considerably with chemotherapy. The existence of circadian disruption during the treatment was linked to greater fatigue and weight loss, two of the worst side effects of chemotherapy.

The circadian system responded to chemotherapy treatment in four ways: the activity-rest rhythm remained stable despite chemotherapy (9.5% of patients); there was improvement (14.3% of patients); alteration in the rhythm followed by complete recovery (31% of the patients); or sustained deterioration (45% of the patients), possibly due to inadequate chronotherapy dosing and/or timing.

"Minimizing circadian disruption through the personalization of chronotherapy delivery could help to improve tolerance to chemotherapy and make the treatment more effective," said Ortiz.

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