Rasmussen, C.L., Olsen, M.K., Johnsen, A.T., Petersen, M.A., Lindholm, H., Andersen, L., . . . Pedersen, L. (2015). Effects of melatonin on physical fatigue and other symptoms in patients with advanced cancer receiving palliative care: A double-blind placebo-controlled crossover trial. Cancer, 121, 3727–3736. 

To determine if oral melatonin administered at night would reduce fatigue and improve sleep in patients with advanced cancer treated in a palliative care facility

This was a two-part trial. In part one, patients received either melatonin (20 mg) or placebo followed by a washout of two days, then crossed over and received the opposite of the first week of treatment. Part two was an open-label study of patients who completed part one and chose to continue melatonin. Study questionnaires were completed at the beginning and end of each treatment period (days 1, 7 ,10, and 17). In part two, study measures were obtained weekly. Patients were randomly assigned to the order in which they received melatonin or placebo.

• N = 34 by ITT analysis  
• MEAN AGE = 64.5 years
• AGE RANGE = 35–84 years
• MALES: 38%, FEMALES: 62%
• KEY DISEASE CHARACTERISTICS: Breast and lung cancer were most common. All had advanced disease.

• SITE: Single site  
• SETTING TYPE: Inpatient  
• LOCATION: Denmark

• PHASE OF CARE: Active antitumor treatment

• Randomized, placebo-controlled, crossover trial

• Multidimensional Fatigue Inventory (MFI)
• EORTC Cancer Quality of Life Core 15 for palliative care patients (EORTC-QLQ-C15-PAL)

No significant differences were noted in patient outcomes between the placebo and melatonin groups.

Melatonin administration did not improve fatigue, insomnia, or other symptoms in patients with advanced cancer.

• Small sample (less than 100)
• Subject withdrawals 10% or greater
• Multiple and frequent use of the same measurement tools

This study did not show any improvement in fatigue or sleep as a result of melatonin.