A Double-Blind Placebo Controlled Trial of Testosterone Replacement for Fatigue in Males With Advanced Cancer (TH307-B)

Abstract

blinding and absence of placebo controls. Research Objectives. The primary objective of this study was to compare melatonin to placebo for appetite in patients with cachexia. Method. A randomized, double-blind, 28 day trial of melatonin 20 mg vs. placebo in patients with advanced lung or gastrointestinal cancer, appetite scores > 3 on a 0 to 10 scale (10 1⁄4 worst appetite) and a weight loss $ 5% within 6 months. The assessments included weight, symptom severity by Edmonton Symptom Assessment Scale (ESAS), and quality of life by the Functional Assessment of Anorexia/Cachexia Therapy (FAACT). Differences between groups from baseline to day 28 were analyzed using one-sided two sample t tests (appetite, pain and well-being) or Wilcoxon two-sample tests for the other variables. Interim analysis at half point had a Lan-DeMets monitoring boundary with an O’Brien-Fleming stopping rule. Result. After interim analysis of 48 patients, the study was closed by the Data Safety Monitoring Board for futility. There were no significant differences between groups in appetite (p 1⁄4 0.78), weight (p 1⁄4 0.17), FAACT score (p 1⁄4 0.95), insomnia (p 1⁄4 0.62) or other symptoms measured by the ESAS from baseline to day 28. No significant toxicities were observed. Conclusion. In cachectic patients with advanced cancer, 20 mg oral melatonin at night does not improve appetite, weight, or quality of life compared to placebo. Implications for Research, Policy, or Practice. A commonly used supplement for symptoms in advanced cancer was ineffective in this trial. However, systematic reviews of melatonin suggest the supplement may be effective for symptoms and other clinical outcomes in patients receiving anti-tumor therapy. Further research may be justified in these patient groups.