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Phase I dose‐finding study for melatonin in pediatric oncology patients with relapsed solid tumors
Author(s) -
Johnston Donna L.,
Zupanec Susan,
Nicksy Darcy,
Morgenstern Daniel,
Narendran Aru,
Deyell Rebecca J.,
Samson Yvan,
Wu Bing,
Baruchel Sylvain
Publication year - 2019
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.27676
Subject(s) - melatonin , medicine , tolerability , maximum tolerated dose , adverse effect , anorexia , concomitant , pediatric cancer , population , chemotherapy , cancer , oncology , environmental health
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.