Placebo-Controlled, Double-Blind, Randomized Pilot Study to Evaluate the Effects of Low-Dose Naltrexone on Quality of Life and Fatigue in Newly Diagnosed High-Grade Glioma (P4.210)

Abstract

Background: During the illness trajectory of high-grade glioma (HGG), patients experience diminished quality of life (QoL) and fatigue associated with diagnosis and treatment, in particular chemoradiation. Naltrexone, an orally semisynthetic opiate antagonist, is FDA- approved for treatment of heroin/ alcohol addiction, but there have been observations that low dose naltrexone (LDN) can mitigate fatigue and stress in fibromyalgia and multiple sclerosis patients. While the mechanism is largely not understood, LDN is thought to work as a partial agonist and lead to transient increases in met-enkephalin and β-endorphins, which in turn can theoretically improve energy and QoL. Objective: Because of the lack of toxicity and paucity of agents to mitigate fatigue and improve QoL, we sought to evaluate LDN effect of QoL and fatigue in newly diagnosed HGG. Methods: In a placebo-controlled, double-blind, randomized study, HGG patients received placebo or LDN (4.5 mg po qhs). Treatment began on the first day of chemoradiation and continued for 16 wks. The primary objective was to compare patient-reported outcome measures of QoL, including the Functional Assessment of Cancer Therapy-Brain (FACT-Br) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Safety of LDN was a secondary outcome with standard laboratory testing and adverse event reporting. Results: 110 subjects were randomized to LDN (54) or placebo (56). Subjects were: WHO grade IV (85[percnt]), male (56[percnt]), KPS 90-100 (51[percnt]), grossly resected (55[percnt]) and mean age of 56 years. Percent decrease from baseline at 16 weeks was not significantly different for FACT-Br [T-test p=0.4938; Mean=1.5 (LDN), 5.0 (placebo)]. Percent decrease from baseline at 16 weeks was not significantly different for FACIT-F [Wilcoxon p=0.3082; Median=6.9 (LDN), 11.8 (placebo)]. Adverse events were seen in similar frequencies in both groups. Conclusions: Though LDN is safe to administer, LDN has no impact on QoL or fatigue in HGG patients.

Disclosure: Dr. Peters has nothing to disclose. Dr. Affronti has nothing to disclose. Dr. Woodring has nothing to disclose. Dr. Lipp has nothing to disclose. Dr. Healy has nothing to disclose. Dr. McSherry has nothing to disclose. Dr. Herndon has nothing to disclose. Dr. Flahiff has nothing to disclose. Dr. Miller has nothing to disclose. Dr. Freeman has nothing to disclose. Dr. Minchew has nothing to disclose. Dr. Zalutsky has nothing to disclose. Dr. Taylor has nothing to disclose. Dr. Boulton has nothing to disclose. Dr. Randazzo has nothing to disclose. Dr. DesJardins has nothing to disclose. Dr. Vlahovic has nothing to disclose. Dr. Bigner has nothing to disclose. Dr. Friedman has nothing to disclose.