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
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: Background: Cancer-related cognitive impairment (CRCI) affects a substantial proportion of breast cancer survivors (BCS) and effective pharmacologic interventions are lacking. Oxaloacetate (OAA), 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 BCS 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 endpoint 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: <0.0001), with improvement from the impaired to the normative range. Statistically significant improvements were also observed in total fatigue (p<.0001), mental fatigue (p<.0001), and physical function (p=.0003), with a trend toward improvement in insomnia (p=.09). Neuropsychological testing showed improvements in executive function and processing speed. Oxaloacetate was generally well-tolerated; gastrointestinal symptoms were the most common adverse events, leading to treatment discontinuation in two participants. There were no serious adverse events. Conclusions: Oxaloacetate treatment led to significant improvements in perceived cognitive impairment, fatigue, and physical functioning among BCS with CRCI, with acceptable tolerability. These findings support further investigation in a randomized, placebo-controlled trial to confirm efficacy.
Source: JCO oncology advances.
DOI: 10.1200/oa-26-00063
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223059902