Phase I dose-finding study for melatonin in pediatric oncology patients with relapsed solid tumors
Abstract
BACKGROUND: Melatonin is a natural health product used for sleep disturbances. In preliminary studies of adults with advanced cancer, 20 mg of melatonin daily was associated with reduction in anorexia and weight loss-symptoms that also impact pediatric oncology patients. High doses of melatonin have not been studied in pediatrics. METHODS: This was a multicenter single-arm phase I dose-escalation study utilizing a 3 + 3 design to determine the safety and tolerability of escalating doses of melatonin in pediatric oncology patients with relapsed solid tumors. Melatonin was given for 8 weeks at three dose levels-0.075 mg/kg (maximum 5 mg), 0.15 mg/kg (maximum 10 mg), and 0.3 mg/kg (maximum 20 mg). RESULTS: Melatonin was well tolerated at all three dose levels with no significant adverse events or dose-limiting toxicities. The only grade 3/4 toxicities were myelosuppression, which was attributed to the concomitant chemotherapy and occurred at all dose levels. Weight gain occurred in seven of nine patients, with a median increase of 1.1 kg (range -3.3 to 4.5) or 3.4% (range -10.2 to 8.7), with two patients losing weight (one in dose level 1 and one level 3). CONCLUSIONS: Melatonin is well tolerated at a dose of 0.3 mg/kg (maximum 20 mg), in the pediatric population. This study provides the background for further study of high-dose melatonin in pediatric oncology patients.
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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 [182]
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- Authors
- Johnston, D. L., Zupanec, S., Nicksy, D., Morgenstern, D., Narendran, A., Deyell, R. J., Samson, Y., Wu, B., & Baruchel, S.
- Affiliations
- Children's Hospital of Eastern Ontario (CA)
- University of Toronto (CA)
- Alberta Children's Hospital (CA)
- BC Children's Hospital (CA)
- Centre Hospitalier Universitaire Sainte-Justine (CA)
- Corresponding author
- Johnston, Donna L.
- Venue
- Pediatric Blood & Cancer
- Publisher
- Wiley
- Published
- 2019-02-20
- Volume
- 66
- Issue
- 6
- Pages
- e27676-e27676
- ISSN
- 1545-5009 (ISSN-L)
- 1545-5017
- OpenAlex
- W2917942725
- Cited by
- 8
- References
- 25
- Citations by year
- 2024: 2 · 2023: 3 · 2022: 1 · 2020: 1 · 2019: 1
- FWCI
- 0.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pediatric Blood & Cancer (publishedVersion)
- PubMed (publishedVersion)
- Funders
- C17 Research Network
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Health Sciences › Medicine › Oncology › Cancer survivorship and care
- Keywords
- melatonin, pediatric oncology, relapsed solid tumors, dose escalation, safety and tolerability, myelosuppression, weight gain, sleep disorders, anorexia, weight loss, natural health products
- MeSH terms
- Adolescent, Anorexia, Antineoplastic Combined Chemotherapy Protocols, Antioxidants, Child, Child, Preschool, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Humans, Male, Melatonin, Neoplasms, Prognosis, Sleep Wake Disorders, Weight Loss, Maximum Tolerated Dose
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