Low-dose Naltrexone in newly diagnosed high-grade glioma: placebo-controlled, double-blind, randomized pilot study
Katherine Peters, Mary Affronti, Sarah Woodring, Eric Lipp, Patrick Healy, Frances McSherry, James Herndon, II, Charlene Flahiff, Elizabeth Miller, Maria Freeman, Janet Minchew, Ben Zalutsky, Bonnie Taylor, Susan Boulton, Dina Randazzo, Annick Desjardins, Gordana Vlahovic, Darell Bigner, Henry Friedman
Duke University Medical Center, Durham, NC, USA
At diagnosis and throughout disease course, patients with high-grade glioma (HGG) experience a diminished quality of life (QoL), increase in fatigue, and reduction in cognition. Naltrexone, an orally semisynthetic opiate antagonist, is FDA-approved for treatment of heroin/ alcohol addiction, and low dose naltrexone (LDN) has been observed to improve QoL and lower fatigue in other neurological illnesses, such as multiple sclerosis. LDN is believed to function as a partial agonist and can lead to shifts in neurochemicals that reduce fatigue. Based on this, we sought to study whether LDN has an impact on QoL, fatigue, sleepiness, and cognition in patients with HGG. In a placebo-controlled, double-blind, randomized study, 110 HGG patients were randomized to receive placebo (N=56) or LDN 4.5 mg orally at night (N=54). Treatment was initiated at day 1 of concurrent radiation and temozolomide and continued for 16 weeks. Change from baseline was evaluated in all study assessments including patient-reported outcomes of QoL (Functional Assessment of Cancer Therapy-Brain), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue), sleepiness (Epworth Sleepiness Scale), depression (Beck Depression Inventory II), and cognitive testing. Safety of LDN was monitored with standard laboratory testing and adverse event reporting. Demographics were WHO grade IV (85%), male (56%), KPS 90-100 (51%), grossly resected (55%) and mean age of 56 years. For all QoL, fatigue, depression, and cognition measures, change from baseline at 16 weeks was not significantly different in patients receiving LDN or placebo. At 16 weeks, LDN patients reported a significantly greater increase in sleepiness from baseline compared to placebo (p=0.0088). Adverse events were seen in similar frequencies for LDN and placebo. Of note, overall survival did not significantly differ between treatment groups. While LDN is safe to administer, LDN has no effect on QoL, fatigue, cognition, or survival, but may increase sedation, in HGG patients.