Phase 2 trial of anhydrous enol-oxaloacetate for improving cognitive complaints in breast cancer survivors

Prof. Patricia Ganz

Cancer-related cognitive impairment (CRCI) affects a substantial proportion of breast cancer survivors (BCSs), and effective pharmacologic interventions are lacking. Oxaloacetate is an naturally occurring metabolic intermediate with glutamate-scavenging and anti-inflammatory properties. A phase 2 trial at David Geffen School of Medicine at the University of California Los Angeles evaluated safety and efficacy of oxaloacetate for improving cognitive complaints in BCSs with moderate to severe CRCI. The trial enrolled early-stage BCSs who were 1 to 5 years post-primary treatment and reported significant cognitive complaints on the PROMIA Cognitive Function questionnaire. Particpants received oxaloacetate 500 mg orally twice daily for 8 weeks. The primary endpoint was improvement in perceived cognitive impairment, measured by the FACT-Cog PCI score at baseline (T1), day 29 (T2) and day 57 (T3). Eighteen participants were enrolled; 16 completed the intervention. All evaluable participants demonstrated clinically and statistically significant improvement in perceived cognitive impairment (mean FACT-Cog PCI change +26.4 points; p<0.0001) , with improvement from the impaired to the normative range. Statistically significant improvements were also observed in total fatigue, mental fatigue, and physical function, with a trend toward improvement in insomnia. Oxaloacetate was generally well-tolerated; GI symptoms were the most common adverse events. There were no serious adverse events. The authors conclude that oxaloacetate treatment led to significant improvements in perceived cognitive impairment, fatigue, and physiscal functioing among BCSs with CRCI, with acceptable tolerability.