A randomized placebo-controlled trial of melatonin for poor appetite in advanced cancer patients.

Abstract

TPS319 Background: Although initially thought to be synthesized exclusively in the pineal gland and primarily involved as a circadian messenger of light and dark, melatonin is now recognized to have multiple actions and synthesized in various tissues including lymphocytes and the gastrointestinal tract. Melatonin supplementation stimulates appetite in animals, and its presence in the digestive tract is associated with intestinal transit and nutrient absorption. Altered levels of melatonin are found in patients with a range of cancers and preliminary nonrandomized studies in patients with advanced solid tumors suggest melatonin may attenuate weight loss, anorexia, fatigue, and depression. These studies are limited by a lack of blinding and the absence of placebo controls. Melatonin appears to be safe at doses up to 300 mg daily in noncancer patients and after prolonged use in normal volunteers. Methods: Eligibility criteria include patients with solid gastrointestinal tumors or lung cancer, a ≥ 5% involuntary weight loss within the last 6 months and anorexia > 3 (0 is best and 10 is worst) on the Edmonton Symptom Assessment Scale (ESAS). Patients with untreated endocrine dysfunction (hypoadrenalism and thyroid abnormalities) are excluded and nutritional impact symptoms such as nausea, diarrhea, mucositis, constipation, or clinical depression should be resolved or stable for ≥2 weeksat the time of inclusion. Design is a double-blind placebo-controlled trial of 20 mg melatonin vs. placebo for 4 weeks. At the end of 4 weeks, all study patients are given the opportunity to take 20 mg melatonin at night for an additional 4 weeks. The primary objective at 4 weeks is to determine whether melatonin improves appetite in patients with advanced lung cancer or gastrointestinal cancer as defined by a decrease of 1.5 in appetite score from baseline (on ESAS). The secondary objectives include body weight, lean body mass (by bioelectrical impedance and bone free arm muscle area), caloric intake (24 hour diet recall), resting energy expenditure (indirect calorimetry) and serum levels of C-reactive protein. Current accrual stands at 62 patients, and we anticipate enrolling 126. No significant financial relationships to disclose.