Effects of melatonin on physical fatigue and other symptoms in patients with advanced cancer receiving palliative care: A double-blind placebo-controlled crossover trial
Open accessAbstract
BACKGROUND: Patients with advanced cancer often experience fatigue and other symptoms that negatively impact their quality of life. The current trial investigated the effect of melatonin on fatigue and other symptoms in patients with advanced cancer. METHODS: Patients who were aged ≥18 years, had a histologically confirmed stage IV cancer (TNM Classification), and who reported feeling significantly tired were recruited from the palliative care unit at the study institution. The study was a double-blind, randomized, placebo-controlled crossover trial. Patients received 1 week of melatonin at a dose of 20 mg or a placebo orally each night, before crossing over and receiving the opposite treatment for 1 week. Between the 2 periods, a washout period of 2 days was implemented. Outcomes were measured using the Multidimensional Fatigue Inventory (MFI-20) and The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Physical fatigue from the MFI-20 was the primary outcome. The primary analysis was a complete complier analysis (ie, it included only those patients who had consumed at least 5 capsules per week and who had answered the MFI-20 on days 1, 7, 10, and 17). Sensitivity analysis using multiple imputations including all randomized patients and all patients completing the intervention were conducted. RESULTS: A total of 72 patients were randomized. Fifty patients completed the intervention and 44 patients were complete compliers. No significant differences between the placebo and melatonin periods were found for physical fatigue, secondary outcomes, or explorative outcomes. CONCLUSIONS: In the current study, oral melatonin at a dose of 20 mg was not found to improve fatigue or other symptoms in patients with advanced cancer.
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Other studies since these pivotal publications have used 50 mg daily as a reference dose.
“Other studies since these pivotal publications have used this dose as a reference [181,182,183,184].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [183]
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Cites
Smets, E. M. A., Garssen, B., Bonke, B., & de Haes, J. C. J. M. (1995) · Journal of Psychosomatic Research · doi:10.1016/0022-3999(94)00125-o · Cited by 3,622 · see citing works
Brzezinski, A. (1997) · New England Journal of Medicine · doi:10.1056/nejm199701163360306 · Cited by 1,549 · see citing works
Grøenvold, M., Petersen, M. A., Aaronson, N. K., Arrarás, J. I., Blazeby, J. M., Bottomley, A., Fayers, P. M., de Graeff, A., Hammerlid, E. B., Kaasa, S., et al. (2005) · European Journal of Cancer · doi:10.1016/j.ejca.2005.06.022 · Cited by 678 · see citing works
The interpretation of scores from the EORTC quality of life questionnaire QLQ-C30
King, M. T. (1996) · Quality of Life Research · doi:10.1007/bf00439229 · Cited by 666 · see citing works
Walsh, D., Donnelly, S. M., & Rybicki, L. A. (2000) · Supportive Care in Cancer · doi:10.1007/s005200050281 · Cited by 620 · see citing works
Dollins, A. B., Zhdanova, I. V., Wurtman, R. J., Lynch, H. J., & Deng, M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.5.1824 · Cited by 578 · see citing works
Mormont, M., Waterhouse, J. M., Bleuzen, P., Giacchetti, S., Jami, A., Bogdan, A., Lellouch, J., Misset, J. L., Touitou, Y., & Lévi, F. (2000) · PubMed · Cited by 428 · see citing works
Design, analysis, and presentation of crossover trials
Mills, E. J., Chan, A., Wu, P., Vail, A., Guyatt, G. H., & Altman, D. G. (2009) · Trials · doi:10.1186/1745-6215-10-27 · Cited by 323 · see citing works
Multiple Imputation UsingSASSoftware
Yuan, Y. (2011) · Journal of Statistical Software · doi:10.18637/jss.v045.i06 · Cited by 315 · see citing works
Koller, M. T., Aaronson, N. K., Blazeby, J. M., Bottomley, A., Dewolf, L., Fayers, P. M., Johnson, C. A., Ramage, J. K., SCOTT, N. W., & West, K. (2007) · European Journal of Cancer · doi:10.1016/j.ejca.2007.05.029 · Cited by 302 · see citing works
Further validation of the Multidimensional Fatigue Inventory in a US adult population sample
Lin, J.-M. S., Brimmer, D. J., Maloney, E. M., Nyarko, E., BeLue, R., & Reeves, W. C. (2009) · Population Health Metrics · doi:10.1186/1478-7954-7-18 · Cited by 255 · see citing works
Lissoni, P., Barni, S., Mandalà, M., et al. (1999) · European Journal of Cancer · doi:10.1016/s0959-8049(99)00159-8 · Cited by 253 · see citing works
The Absolute Bioavailability of Oral Melatonin
DeMuro, R. L., Nafziger, A. N., Blask, D. E., Menhinick, A. M., & Bertino, J. (2000) · The Journal of Clinical Pharmacology · doi:10.1177/00912700022009422 · Cited by 243 · see citing works
Putting Cancer to Sleep at Night: The Neuroendocrine/Circadian Melatonin Signal
Blask, D. E., Dauchy, R. T., & Sauer, L. A. (2005) · Endocrine · doi:10.1385/endo:27:2:179 · Cited by 238 · see citing works
Melatonin: therapeutic and clinical utilization
Altun, A., & Ugur-Altun, B. (2007) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2006.01191.x · Cited by 218 · see citing works
Deacon, S., & Arendt, J. (1995) · Brain Research · doi:10.1016/0006-8993(95)96872-i · Cited by 203 · see citing works
Melatonin in Cancer Management: Progress and Promise
Jung, B., & Ahmad, N. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-1776 · Cited by 197 · see citing works
Psychometric Testing of Fatigue Instruments for Use With Cancer Patients
Meek, P., Nail, L. M., Barsevick, A. M., Schwartz, A. L., Stephen, S. A., Whitmer, K. R., Beck, S. L., Jones, L. S., & Walker, B. L. (2000) · Nursing Research · doi:10.1097/00006199-200007000-00001 · Cited by 185 · see citing works
Melatonin as Adjuvant Cancer Care With and Without Chemotherapy
Seely, D., Wu, P., Fritz, H., Kennedy, D. A., Tsui, T. C. O., SEELY, A. J. E., & Mills, E. J. (2011) · Integrative Cancer Therapies · doi:10.1177/1534735411425484 · Cited by 176 · see citing works
Melatonin in Medically Ill Patients With Insomnia
Andrade, C., Srihari, B. S., Reddy, K. P., & Chandramma, L. (2001) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v62n0109 · Cited by 158 · see citing works
Is there a role for melatonin in supportive care?
Lissoni, P. (2002) · Supportive Care in Cancer · doi:10.1007/s005200100281 · Cited by 153 · see citing works
Contributing Factors to Physical Symptoms in Terminally-Ill Cancer Patients
Morita, T., Tsunoda, J., Inoue, S., & Chihara, S. (1999) · Journal of Pain and Symptom Management · doi:10.1016/s0885-3924(99)00096-2 · Cited by 141 · see citing works
Self‐assessment in cancer patients referred to palliative care
Strömgren, A. S., Goldschmidt, D., Grøenvold, M., Petersen, M. A., Jensen, P. T., Pedersen, L., Hoermann, L., Helleberg, C., & Sjøgren, P. (2002) · Cancer · doi:10.1002/cncr.10222 · Cited by 138 · see citing works
Self-citationFabbro, E. D., Dev, R., Hui, D., Palmer, L. J., & Bruera, E. D. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.43.6766 · Cited by 122 · see citing works
Lissoni, P., Paolorossi, F., Ardizzoia, A., Barni, S., Chilelli, M. G., Mancuso, M., Tancini, G., Conti, A. M. F., & Maestroni, G. J. M. (1997) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1997.tb00329.x · Cited by 115 · see citing works
Quality of life in terminal care—with special reference to age, gender and marital status
Hagelin, C. L., Seiger, Å., & Fürst, C. J. (2005) · Supportive Care in Cancer · doi:10.1007/s00520-005-0886-4 · Cited by 114 · see citing works
Symptom Priority and Course of Symptomatology in Specialized Palliative Care
Strömgren, A. S., Sjøgren, P., Goldschmidt, D., Petersen, M. A., Pedersen, L., & Grøenvold, M. (2006) · Journal of Pain and Symptom Management · doi:10.1016/j.jpainsymman.2005.07.007 · Cited by 110 · see citing works
Self-citationThe therapeutic potential of melatonin: a review of the science.
Malhotra, S., Sawhney, G., & Pandhi, P. (2004) · PubMed Central · Cited by 103 · see citing works
Bartsch, C., Bartsch, H., Schmidt, A., Ilg, S., Bichler, K., & Flüchter, S. (1992) · Clinica Chimica Acta · doi:10.1016/0009-8981(92)90164-l · Cited by 102 · see citing works
In-patient rehabilitation of lung cancer patients—a prospective study
Riesenberg, H., & Lübbe, A. S. (2009) · Supportive Care in Cancer · doi:10.1007/s00520-009-0727-y · Cited by 102 · see citing works
Treatment of cancer chemotherapy-induced toxicity with the pineal hormone melatonin
Lissoni, P., Tancini, G., Barni, S., et al. (1997) · Supportive Care in Cancer · doi:10.1007/bf01262569 · Cited by 95 · see citing works
Fernandes, R., Stone, P. C., Andrews, P. L. R., Morgan, R., & Sharma, S. (2006) · Journal of Pain and Symptom Management · doi:10.1016/j.jpainsymman.2006.03.014 · Cited by 81 · see citing works
Small cell carcinoma cell lines contain opioid peptides and receptors
Roth, K. A., & Barchas, J. D. (1986) · Cancer · doi:10.1002/1097-0142(19860215)57:4 · Cited by 66 · see citing works
Melatonin in pathogenesis and therapy of cancer
Ravindra, T., Lakshmi, N. D., & Ahuja, Y. (2006) · Indian Journal of Medical Sciences · doi:10.4103/0019-5359.28983 · Cited by 55 · see citing works
Lissoni, P., Barni, S., Rovelli, F., et al. (1993) · European Journal of Cancer · doi:10.1016/0959-8049(93)90170-k · Cited by 42 · see citing works
Littlewood, T. J., Kallich, J. D., Miguel, J. F. S., Hendricks, L., & Hedenus, M. (2006) · Journal of Pain and Symptom Management · doi:10.1016/j.jpainsymman.2005.08.013 · Cited by 42 · see citing works
Searching for New Options for Treating Insomnia: Are Melatonin and Ramelteon Beneficial?
Bellon, A. (2006) · Journal of Psychiatric Practice · doi:10.1097/00131746-200607000-00005 · Cited by 41 · see citing works
Hedlund, L., Gyllensten, A. L., & Hansson, L. I. (2014) · Community Mental Health Journal · doi:10.1007/s10597-014-9746-3 · Cited by 31 · see citing works
Lissoni, P., agrave, M. M., & Brivio, F. (2000) · European Urology · doi:10.1159/000020263 · Cited by 29 · see citing works
Lissoni, P., Barni, S., Fossati, V., et al. (1995) · Supportive Care in Cancer · doi:10.1007/bf00368890 · Cited by 26 · see citing works
Eichler, C., Multhaupt, P., Multhaupt, S., Sauerwald, A., Wolff, F., & Warm, M. (2015) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2015.16.3.1063 · Cited by 24 · see citing works
Spiegel, D. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.16.2008 · Cited by 22 · see citing works
Neurobiological effects of melatonin as related to cancer
Hoang, B. X., Shaw, D. G., Pham, P. T. K., & Levine, S. A. (2007) · European Journal of Cancer Prevention · doi:10.1097/cej.0b013e32801023dc · Cited by 15 · see citing works
Dehais, C., Souvannavong, V., Nguyen, B. K., et al. (2011) · Revue Neurologique · doi:10.1016/j.neurol.2011.01.016 · Cited by 4 · see citing works
Flagged first, then by citations
Research works printed but not linked: 6
- Dollins AB, Zhdanova IV, Wurtman RJ, Lynch HJ, Deng MH. Effect of inducing nocturnal serum melatonin concentrations in day- time on sleep, mood, body temperature, and performance. Proc Natl Acad Sci USA. 1994;91:1824-1828.
- Lissoni P, Viviani S, Bajetta E, et al. A clinical study of the pineal gland activity in oncologic patients. Cancer. 1986;57:837-842.
- Edge S, Byrd DR, Compton CC, et al.(editors) AJCC Cancer Stag- ing Manual 7th Edition, London: New York, NY: Springer.
- Pocock SJ. Clinical Trials: A Practical Approach, Crossover Trials, Chichester, UK: John Wiley & Sons Ltd, 1996:110-122.
- Yuan Y. Multiple imputation using SAS software. J Stat Softw. 2011;45:1-25.
- Dehais C, Souvannavong V, Nguyen BK, et al. An evaluation of fa- tigue in patients with glioblastoma relapse treated with the combina- tion of irinotecan-bevacizumab [in French]. Rev Neurol (Paris). 2011;167:841-846.
Cited by
Sorted by citations
Minich, D. M., Henning, M., Darley, C., Fahoum, M., Schuler, C. B., & Frame, J. (2022) · Nutrients · doi:10.3390/nu14193934 · Cited by 176 · see citing works
- Authors
- Lund Rasmussen, C., Klee Olsen, M., Thit Johnsen, A., Aagaard Petersen, M., Lindholm, H., Andersen, L., Villadsen, B., Groenvold, M., & Pedersen, L.
- Affiliations
- Research Unit, Department of Palliative Medicine Bispebjerg Hospital Copenhagen Denmark
- Bispebjerg Hospital (DK)
- Venue
- Cancer
- Publisher
- Wiley
- Published
- 2015-07-15
- Volume
- 121
- Issue
- 20
- Pages
- 3727-3736
- ISSN
- 0008-543X (ISSN-L)
- 1097-0142
- OpenAlex
- W1847108160
- Cited by
- 52
- References
- 44
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 8 · 2022: 7 · 2021: 7 · 2020: 5 · 2019: 1 · 2018: 7 · 2017: 2 · 2016: 1
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- IM Daehnfeldt Foundation
- Aase and Ejnar Danielsens Foundation
- Beckett Foundation
- Danish Cancer Society (journal number A1013)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Oncology › Cancer survivorship and care
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Palliative and Oncologic Care
- Keywords
- melatonin, physical fatigue, advanced cancer, palliative care, symptom management, quality of life, Multidimensional Fatigue Inventory, EORTC QLQ-C30, crossover trial
- MeSH terms
- Administration, Oral, Adult, Aged, Aged, 80 and over, Double-Blind Method, Drug Administration Schedule, Fatigue, Female, Humans, Male, Melatonin, Middle Aged, Neoplasms, Palliative Care, Patient Compliance, Quality of Life, Cross-Over Studies
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