{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T05:08:57Z","timestamp":1789189737409,"version":"build-2803163510"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T00:00:00Z","timestamp":1694476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"VCU Massey Cancer Center Biostatistics"},{"name":"NIH-NCI Cancer Center","award":["P30 CA016059"],"award-info":[{"award-number":["P30 CA016059"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Fatigue is common in patients undergoing radiotherapy (RT) and can significantly impact quality of life. Melatonin, a safe inexpensive natural supplement, may improve symptoms and attenuate the side effects of RT. The purpose of this randomized double-blind placebo-controlled phase III trial was to assess the effects of melatonin for preventing fatigue and other symptoms in patients with breast cancer undergoing RT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Female early stage or Ductal carcinoma in situ patients with breast cancer \u226518 years of age with Eastern Cooperative Oncology Group (ECOG) performance status &amp;lt;3, hemoglobin \u22659 g\/dL, planned for outpatient RT treatment with curative intent, were randomized 1:1 to melatonin 20 mg or placebo, orally, starting the night before RT initiation until 2 weeks post-RT. Randomization was stratified according to treatment duration (&amp;lt;3 weeks, \u22653 weeks) and prior chemotherapy. The primary endpoint was the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue scale), and secondary endpoints were FACIT-F subscales, Edmonton Symptom Assessment Scale (ESAS), and Patient-Reported Outcomes Measurement Information System (PROMIS) scores obtained at baseline, and 2 and 8 weeks post-RT. A 2-sided ANOVA F-test at a 4.5% significance level for the primary endpoint was used. Secondary analyses were reported using an F-test at a 5% significance level. The goal was to recruit approximately 140 patients with interim analysis planned mid-recruitment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eighty-five patients were screened for eligibility; 79 patients were randomized: 40 to melatonin and 39 to placebo; 78 patients were treated and included in the interim analysis at the mid-recruitment point. Baseline patient characteristics of age, race, and ECOG performance status were similar in both arms. The treatment effect was studied using a longitudinal mixed effects model with the effect of treatment over time (treatment \u00d7 time) as the primary outcome parameter. The treatment \u00d7 time for FACIT-Fatigue did not demonstrate statistical significance (P-value .83) in the melatonin group compared to placebo. In addition, secondary analyses of FACIT physical, social, emotional, and functional well-being scores did not demonstrate statistical significance (P-values of .35, .06, .62, and .71, respectively). Total PROMIS scores, collected as secondary outcome reported by patients, did not demonstrate statistically significant change over time either (P-value is .34). The other secondary scale, ESAS, was analyzed for each individual item and found to be nonsignificant, anxiety (P\u2005=\u2005.56), well-being (.82), drowsiness (.83), lack of appetite (.35), nausea (.79), pain (.50), shortness of breath (.77), sleep (.45), and tiredness (.56). Depression was the only item demonstrating statistical significance with a decrease of 0.01 unit in the placebo group, a change not considered clinically significant. Melatonin was well-tolerated with no grade 3 or 4 adverse events reported. The most common side effects were headache, somnolence, and abdominal pain. No patients died while participating in this study. Two patients died within a year of study completion from breast cancer recurrence. Sixteen patients withdrew prior to study completion for various reasons including adverse events, hospitalizations unrelated to study drug, RT discontinuation, and COVID-19 precautions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this double-blind placebo-controlled phase III trial, melatonin did not prevent or significantly improve fatigue and other symptoms in patients with early stage breast cancer undergoing RT. The analysis, showing little evidence of an effect, at mid-recruitment, assured early termination of the trial.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyad250","type":"journal-article","created":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T11:33:37Z","timestamp":1692704017000},"page":"e206-e212","source":"Crossref","is-referenced-by-count":28,"title":["Melatonin Supplementation for Cancer-Related Fatigue in Patients With Early Stage Breast Cancer Receiving Radiotherapy: A Double-Blind Placebo-Controlled Trial"],"prefix":"10.1093","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1530-9516","authenticated-orcid":false,"given":"Nitai D","family":"Mukhopadhyay","sequence":"first","affiliation":[{"name":"Department of Biostatistics, Virginia Commonwealth University , Richmond, VA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Khorasanchi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology, Oncology, and Palliative Care, Virginia Commonwealth University , Richmond, VA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudeep","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology, Oncology, and Palliative Care, Virginia Commonwealth University , Richmond, VA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinidhi","family":"Nemani","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology, Oncology, and Palliative Care, Virginia Commonwealth University , Richmond, VA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwendolyn","family":"Parker","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Virginia Commonwealth University , Richmond, VA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Virginia Commonwealth University , Richmond, VA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas W","family":"Arthur","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Virginia Commonwealth University , Richmond, VA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Urdaneta","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Virginia Commonwealth University , Richmond, VA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egidio","family":"Del Fabbro","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology, Oncology, and Palliative Care, Virginia Commonwealth University , Richmond, VA , USA"},{"name":"Department of 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