Effects of Melatonin on Physical Fatigue and Other Symptoms in Patients With Advanced Cancer Receiving Palliative Care: A Double-Blind Placebo-Controlled Crossover Trial
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Is there a role for melatonin in supportive care?
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Clinical Investigation on Melatonin's Anticancer and Supportive Care Properties (2 studies, combined results)
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Prevention of cytokine-induced hypotension in cancer patients by the pineal hormone melatonin
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A Randomized Controlled Trial of Oral Melatonin Supplementation and Breast Cancer Biomarkers
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Effect of Melatonin on Sleep in the Perioperative Period after Breast Cancer Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial
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A Randomized, Controlled, Parallel-Group, Trial on the Effects of Melatonin on Fatigue Associated with Breast Cancer and Its Adjuvant Treatments
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A Randomized, Controlled, Parallel-Group, Trial on the Long-term Effects of Melatonin on Fatigue Associated With Breast Cancer and Its Adjuvant Treatments
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Melatonin Supplementation for Cancer-Related Fatigue in Patients With Early Stage Breast Cancer Receiving Radiotherapy: A Double-Blind Placebo-Controlled Trial
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Quality-of-life outcomes following topical melatonin application against acute radiation dermatitis in patients with early breast cancer: A double-blind, randomized, placebo-controlled trial
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Effect of melatonin cream on acute radiation dermatitis in patients with primary breast cancer: A double‐blind, randomized, placebo‐controlled trial
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A Randomized Double-Blind Placebo-Controlled Trial of the Effectiveness of Melatonin on Neurocognition and Sleep in Survivors of Childhood Cancer
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Randomized placebo-controlled phase II trial of high-dose melatonin mucoadhesive oral gel for the prevention and treatment of oral mucositis in patients with head and neck cancer undergoing radiation therapy concurrent with systemic treatment
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Double-blind randomized study on the myeloprotective effect of melatonin in combination with carboplatin and etoposide in advanced lung cancer
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Biochemotherapy with standard chemotherapies plus the pineal hormone melatonin in the treatment of advanced solid neoplasms
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Decreased Toxicity and Increased Efficacy of Cancer Chemotherapy Using the Pineal Hormone Melatonin in Metastatic Solid Tumour Patients with Poor Clinical Status
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Treatment of cancer chemotherapy-induced toxicity with the pineal hormone melatonin
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Impact of multicomponent, nonpharmacologic interventions on perioperative cortisol and melatonin levels and postoperative delirium in elderly oral cancer patients
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The protective effects of melatonin on blood cell counts of rectal cancer patients following radio-chemotherapy: a randomized controlled trial
IL-2: 6 days/week for 4 weeks; TNF: 5 consecutive days; Melatonin: starting 7 days prior to cytokine injection
Hypotension occurrence, other toxicities, tumor response
Hypotension was significantly less frequent in patients treated with melatonin + cytokine vs cytokine alone (IL-2: 2/46 vs 11/45, p<0.05; TNF: 1/12 vs 10/13, p<0.01)
Melatonin may prevent hypotension occurring during cancer immunotherapy with IL-2 or TNF, possibly by inhibiting NO production
Melatonin group had significantly increased sleep efficiency and reduced wake after sleep onset for the entire 2-week postoperative period. No other significant differences for actigraphy determined sleep outcomes or subjective outcome parameters.
Melatonin significantly changed sleep efficiency and wake after sleep onset after surgery, but had no effects on other objective sleep outcomes or on subjective sleep quality.
From first radiation fraction until last, including weekends
Quality of life (QLQ-C30 and QLQ-BR23 questionnaires), breast symptom scores
No significant difference in breast symptom scores on last day of radiation (p=0.333). Linear model showed melatonin group had significantly lower breast symptom scores over entire study duration (p=0.001)
Topical melatonin did not significantly affect quality of life at last radiation fraction, but patients receiving melatonin experienced fewer breast symptoms overall
Women receiving radiation therapy for primary breast cancer
25 mg/g melatonin and 150 mg/g dimethyl sulfoxide cream
Duration of radiation therapy plus 3 weeks follow-up
1) RTOG acute radiation morbidity scoring criteria for skin<br>2) Pixel analysis of erythema in clinical photographs<br>3) Use of corticosteroid cream
1) No significant difference in RTOG scores at 2 weeks follow-up (p=0.441)<br>2) No significant difference in pixel analysis at 2 weeks follow-up (p=0.890)<br>3) No significant difference in corticosteroid cream use (p=0.055)<br>4) Higher likelihood of low RTOG scores over entire study duration in melatonin group (OR 2.03, 95% CI 1.31-3.16, p=0.0016)
1) Primary outcome showed no difference at 2 weeks follow-up<br>2) RTOG scores over entire study duration showed protective effect of melatonin<br>3) Further studies needed with higher melatonin doses
Adult survivors of childhood cancer (n=580); mean age 33.5 years; 26 years post-diagnosis
3mg time-release melatonin
6 months
Neurocognitive performance, sleep parameters (self-reported and actigraphy-assessed)
No statistically significant differences in neurocognitive performance or sleep in intent-to-treat analyses. Some subgroups showed clinically significant improvements in specific domains.
Melatonin was not associated with improved neurocognitive performance or sleep in intent-to-treat analyses; however, a subset of survivors demonstrated a clinically significant treatment response.
https://pubmed.ncbi.nlm.nih.gov/33738704/
Head and neck
Potentially beneficial
Randomized, phase II, double-blind, placebo-controlled trial
84 patients with locally advanced head and neck cancer
3% melatonin oral gel mouthwashes (1,500 mg/day) vs placebo
8-12 weeks
Incidence and duration of severe oral mucositis (SOM) and ulcerative oral mucositis (UOM)
- Lower SOM incidence in melatonin arm (53% vs 64%, P=0.36)
Significantly lower SOM incidence in cisplatin subgroup (44% vs 78%, P=0.02), SOM duration in cisplatin subgroup (0 vs 22 days, P=0.022) & UOM duration (49 vs 73 days, P=0.014); 3% melatonin oral gel showed a consistent trend to lower incidence and shorter duration of SOM and UOM. Results warrant further investigation in phase III trial.
Higher tumor response rate (34% vs 15%), higher 1-year survival (51% vs 23%), and reduced chemotherapy toxicity in melatonin group
Melatonin may enhance efficacy of chemotherapy and reduce its toxicity in advanced cancer patients with poor clinical status
https://pubmed.ncbi.nlm.nih.gov/9069612/
Metastatic solid tumors
Breast
Lung
Gastrointestinal
Potentially beneficial
Randomized controlled trial
80 patients (32M/48F), median age 59 years
Melatonin 20 mg/day orally in the evening. In combination with the following chemotherapies: cisplatin and etoposide for lung cancer; mitoxantrone for breast cancer; 5-fluorouracil + folates for gastrointestinal tract tumors.
Until disease progression
Chemotherapy-induced toxicity, tumor response
- Significantly less thrombocytopenia in MLT group (p=0.006)<br>- Significantly less asthenia/malaise in MLT group (p=0.0006)<br>- Less stomatitis and neuropathy in MLT group (not statistically significant)<br>- No difference in alopecia and vomiting<br>- Higher tumor regression rate in MLT group (not statistically significant)
Melatonin may prevent some chemotherapy-induced side effects, particularly myelosuppression and neuropathy
https://pubmed.ncbi.nlm.nih.gov/26547518/
Oral
Potentially beneficial
Randomized controlled trial
Elderly patients (65-80 years old) undergoing oral cancer resection surgery
N/A (non-pharmacologic interventions)
Perioperative period
1. Urine melatonin sulfate levels<br>2. Urine cortisol levels<br>3. RASS scores<br>4. Incidence and duration of postoperative delirium<br>5. QoR40 scores
1. Higher melatonin and lower cortisol levels in intervention group<br>2. Lower RASS scores in intervention group<br>3. Lower incidence and duration of postoperative delirium in intervention group<br>4. Higher QoR40 scores in intervention group
Multicomponent, nonpharmacologic interventions ameliorate postoperative sleep and stress disturbances, decrease the incidence of postoperative delirium, and improve recovery quality in elderly oral cancer patients
https://pubmed.ncbi.nlm.nih.gov/30421178/
Rectal
Potentially beneficial
Double-blind placebo-controlled randomized trial
60 rectal cancer patients (20 females, 40 males), age 40-70 years (mean 57.6)
20 mg melatonin daily
28 days
Platelet, neutrophil, white blood cell, red blood cell, and lymphocyte counts
Melatonin group had significantly less reduction in platelets (p=0.04) and neutrophils (p=0.03) compared to placebo. Trends toward less reduction in lymphocytes (p=0.08) and WBCs (p=0.054) in melatonin group.
Melatonin could prevent or minimize unfavorable effects of radiotherapy on blood cell count reductions