Results From a Phase II Single-Arm Trial Evaluating the Safety and Efficacy of Anhydrous Enol-Oxaloacetate on Improving Cognitive Complaints in Breast Cancer Survivors
Patricia A. Ganz, Kathleen Van Dyk, Catherine M. Crespi, Laura Petersen, Mina S. Sedrak, Julienne E. BowerPURPOSE
Cancer-related cognitive impairment (CRCI) affects a substantial proportion of breast cancer survivors (BCSs), yet effective pharmacologic interventions are lacking. Oxaloacetate, a naturally occurring metabolic intermediate with glutamate-scavenging, anti-inflammatory, and mitochondrial bioenergetic properties, was evaluated for its safety and preliminary efficacy in improving cognitive complaints in BCS with moderate to severe CRCI.
METHODS
We conducted a single-arm, phase II trial enrolling early-stage BCSs who were 12 months to 5 years post–primary treatment and reported significant cognitive complaints on the PROMIS Cognitive Function questionnaire. Participants received oxaloacetate 500 mg orally twice daily for 8 weeks. The primary end point was improvement in perceived cognitive impairment, measured by the Functional Assessment of Cancer Therapy-Cognitive Function Perceived Cognitive Impairment (FACT-Cog PCI) score. Secondary outcomes included fatigue, insomnia, psychological symptoms, physical and mental health–related quality of life, neuropsychological test performance, and safety. Simon's two-stage design with subsequent sequential monitoring was used.
RESULTS
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;
CONCLUSION
Oxaloacetate treatment led to significant improvements in perceived cognitive impairment, fatigue, and physical functioning among BCSs with CRCI, with acceptable tolerability. These findings support further investigation in a randomized, placebo-controlled trial to confirm efficacy.