Pasquale F Innominato1,2, Andrew S Lim3, Oxana Palesh4, Mark Clemons5, Maureen Trudeau6, Andrea Eisen6, Cathy Wang6, Alex Kiss7, Kathleen I Pritchard6, Georg A Bjarnason8. 1. INSERM and Paris South University UMR-S0776, Biological Rhythms and Cancers and APHP, Chronotherapy Unit, Department of Oncology, Paul Brousse Hospital, 12-14 Avenue Paul Vaillant Couturier, 94800, Villejuif, France. 2. Cancer Chronotherapy Unit, Warwick Medical School, Coventry, and Department of Oncology, Queen Elisabeth Hospital Brimingham, Brimingham, UK. 3. Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada. 4. Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA, 94305-5717, USA. 5. Division of Medical Oncology, The Ottawa Hospital Cancer Centre, Department of Medicine, University of Ottawa, 501 Smyth Rd, Ottawa, ON, K1H 8L6, Canada. 6. Division of Medical Oncology, Sunnybrook Odette Cancer Centre, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada. 7. Department of Research Design and Biostatistics, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada. 8. Division of Medical Oncology, Sunnybrook Odette Cancer Centre, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada. georg.bjarnason@sunnybrook.ca.
Abstract
BACKGROUND: Fatigue and sleep problems are prevalent in cancer patients and can be associated with disruption of circadian rhythmicity. In this prospective phase II trial, we sought to assess the effect of melatonin on circadian biomarkers, sleep, and quality of life in breast cancer patients. METHODS: Thirty-two patients with metastatic breast cancer, receiving hormonal or trastuzumab therapy, took 5 mg of melatonin at bedtime for 2 months. Before starting and after 2 months on melatonin therapy, sleep and circadian rhythmicity were assessed by actigraphy, diurnal patterns of serum cortisol, and the expression of the core clock genes PER2 and BMAL1 in peripheral blood mononuclear cells. The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire was completed for subjective parameters. RESULTS: Bedtime melatonin was associated with a significant improvement in a marker of objective sleep quality, sleep fragmentation and quantity, subjective sleep, fatigue severity, global quality of life, and social and cognitive functioning scales. Morning clock gene expression was increased following bedtime melatonin intake. Melatonin did not affect actigraphy measure of circadian rhythmicity, or the diurnal cortisol pattern. CONCLUSION: These results invite further investigation of melatonin as a potentially useful therapeutic agent for improving sleep and quality of life in cancer patients.
BACKGROUND:Fatigue and sleep problems are prevalent in cancerpatients and can be associated with disruption of circadian rhythmicity. In this prospective phase II trial, we sought to assess the effect of melatonin on circadian biomarkers, sleep, and quality of life in breast cancerpatients. METHODS: Thirty-two patients with metastatic breast cancer, receiving hormonal or trastuzumab therapy, took 5 mg of melatonin at bedtime for 2 months. Before starting and after 2 months on melatonin therapy, sleep and circadian rhythmicity were assessed by actigraphy, diurnal patterns of serum cortisol, and the expression of the core clock genes PER2 and BMAL1 in peripheral blood mononuclear cells. The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire was completed for subjective parameters. RESULTS: Bedtime melatonin was associated with a significant improvement in a marker of objective sleep quality, sleep fragmentation and quantity, subjective sleep, fatigue severity, global quality of life, and social and cognitive functioning scales. Morning clock gene expression was increased following bedtime melatonin intake. Melatonin did not affect actigraphy measure of circadian rhythmicity, or the diurnal cortisol pattern. CONCLUSION: These results invite further investigation of melatonin as a potentially useful therapeutic agent for improving sleep and quality of life in cancerpatients.
Entities:
Keywords:
Actigraphy; Breast cancer; Circadian; Clock genes; Melatonin; Quality of life; Sleep
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