Table 1.
Benefits of melatonin supplementation for cancer patients
| References | Nb of patients | Endpoints | Design | Dosage MLT | Outcome | Level of evidence |
|---|---|---|---|---|---|---|
| Innominato [37] | 32 | To assess the effect of MLT on circadian biomarkers, sleep, and quality of life in metastatic breast cancer patients | Prospective open label, phase II trial | 5 mg/day taken orally at each patient’s usual bedtime for 2 months | Daily bedtime MLT therapy is associated with reduction in sleep fragmentation, increases in sleep duration, improvements in self-rated sleep quality and improvement in global QoL and pertinent social and cognitive domains, as well as reduction in fatigue severity. Without any short-term toxicity | 1c |
| Lissoni [64] | 1140 | Efficacy of MLT in patients with untreatable advanced solid tumors who had responded to previous standard anticancer therapies and for whom no other effective conventional treatment was available | Randomization according to tumor type: supportive care alone or supportive care + MLT | 20 mg/day during the dark period |
MLT may be effective in the prevention of both cancer progression-related symptoms and chemotherapy-induced toxicity: role in the supportive care of cancer patients MLT may have potential anticancer activity whether given alone or in association with cancer chemotherapy. The 1-year survival curve achieved in patients concomitantly treated with MLT was significantly higher than that for patients who received chemotherapy alone (P < 0.05) |
1b |
| 200 | efficacy of concomitant MLT administration on chemotherapy-induced toxicity and therapeutic activity in previously untreated patients with metastatic solid tumours who had chemo-resistant cancer and a good clinical status | Randomization according to the chemotherapeutic regimen: chemotherapy alone or chemotherapy + MLT | 20 mg/day during the dark period | |||
| Cerea [60] | 30 | To evaluate the influence of a concomitant administration of MLT on CPT-11 therapeutic activity in metastatic colorectal cancer patients progressing after at least one previous chemotherapeutic line containing 5 FU |
Randomization: treatment with CPT11 alone or CPT11 + MLT (CPT11: I.V. 125 mg/m2/week for 9 consecutive week) |
orally 20 mg/day during the dark period of the day | This preliminary study shows that the efficacy of weekly low-dose CPT-11 in pretreated metastatic colorectal cancer patients may be enhanced by a concomitant daily administration of the pineal hormone MLT, according to the results previously reported for other chemotherapeutic agents | 1b |
| Lissoni [64] | 40 |
MLT could amplify the efficacy of TMX in post-menopausal metastatic breast cancer patients with negative ER, |
Randomized study TMX (tamoxifen) versus TMX + MLT |
20 mg/day orally in the evening |
No complete response was seen. Partial response rate was significantly higher in patients treated with TMX plus MLT than in those who received TMX alone The percent of survival at 1 year was significantly higher in patients treated with TMX + MLT than in those treated with TMX alone The association of the pineal hormone MLT may make TMX effective in ER-negative metastatic breast cancer patients |
1b |
| Madsen [63] | 48 | To investigate whether administration of an oral dose of 6 mg MLT before bedtime perioperatively in breast cancer surgery could change sleep outcomes measured by actigraphy |
Double blind, placebo-controlled, randomized clinical trial 27 patients received 6 mg MLT 21 patients received placebo |
6 mg/day approximately 60 min before bedtime 3 nights preoperatively until at least 1 week postoperatively |
Administration of 6 mg oral MLT significantly increased sleep efficiency and reduced waked after sleep onset for the entire 2-week postoperative period But MLT had no effects on other objective sleep outcomes or on subjective sleep quality |
1b |
| Hansen [65] | 54 | Investigate whether MLT could lower the risk of depressive symptoms in women with breast cancer in a three-month period after surgery and assessed the effect of melatonin on subjective parameters (anxiety, sleep, general well-being, fatigue, pain and sleepiness) |
Randomized, double-blind, placebo-controlled trial 28 patients received MLT 26 patients received placebo |
6 mg/day 1 h before bedtime for 1 week preoperatively and 12 weeks ostoperatively | MLT significantly reduced the risk of depressive symptoms in women with breast cancer during a three-month period after surgery | 1b |
| Del Fabbro [67] | 48 | To compare MLT with placebo for appetite improvement in patients with cancer cachexia (patients with advanced lung or GI) | Randomized, double-blind, 28-day trial of MLT 20 mg at night versus placebo | 20 mg/day at night during 28 days |
No significant difference between groups for appetite or other symptoms, weight, FAACT score, toxicity, or survival baseline to day 28 In cachectic patients with advanced cancer, oral MLT 20 mg at night did not improve appetite, weight, or quality of life compared with placebo The trial was stopped after interim analysis |
1b |
| Sookprasert [68] | 151 patients with histologically advanced NSCLC | Health-related QoL assessed with the Functional Assessment of Cancer Therapy—Lung |
Randomized, double-blind, placebo-controlled trial A: 10 mg MLT B: 20 mg MLT C: Placebo |
after 21 h on the first day of chemotherapy treatment and continue for 6 months | When used in combination with chemotherapy, MLT did not significantly affect survival and adverse events of patients with advanced NSCLC, but there was a trend for better HRQoL in the melatonin-treated groups, with a significantly better score in social well-being | 1b |
| Wang [23] | 761 | To observe MLT effect on tumor remission, 1-year survival and side effects due to radiochemotherapy | Meta-analyses of eight randomized clinical trials (patients with solid tumor cancers) | 20 mg orally, once a day |
MLT significantly improved: the complete and partial remission (16.5 vs. 32.6%; RR = 1.95, 95% CI 1.49–2.54; p < 0.00001) 1-year survival rate (28.4 vs. 52.2%; RR = 1.90; 95% CI 1.28–2.83; p = 0.001) decreased radiochemotherapy-related side effects including thrombocytopenia (19.7 vs. 2.2%; RR = 0.13; 95% CI, 0.06–0.28; p < 0.00001), neurotoxicity (15.2 vs. 2.5%; RR = 0.19; 95% CI, 0.09–0.40; p < 0.0001) and fatigue (49.1 vs. 17.2%; RR = 0.37; 95% CI 0.28–0.48; p < 0.00001) |
1a |
| Seely [22] | UK | 1-year mortality, complete response, partial response, stable disease | Meta-analyses of 21 clinical trials (solid tumors) | UK | MLT may benefit cancer patients who are also receiving chemotherapy, radiotherapy, supportive therapy, or palliative therapy by improving survival and ameliorating the side effects of chemotherapy | 1a |
1a: systematic review or meta-analysis of randomized controlled trials (RCT) of good methodological quality and with homogeneity; 1b: individual RCT with narrow CI; 1c: non-controlled studies
MLT melatonin, UK unknown