ACTR-03. A FEASIBILITY TRIAL OF THE MODIFIED ATKINS DIET AND BEVACIZUMAB FOR RECURRENT GLIOBLASTOMA

Abstract

BACKGROUND: We report results of a feasibility trial of the modified Atkins diet (MAD), a form of ketogenic diet (KD), combined with bevacizumab (Bev) for recurrent GBM. The rationale for a KD to treat GBM includes the reduction of glucose availability to this highly glycolytic tumor, reduction of a variety of GBM growth signaling pathways, and increase in tumor-reactive immune responses. Clinical and laboratory data indicate the combination of KD and Bev is more effective than either treatment alone (Reiger et al 2014). Because adherence to the MAD and Bev in patients with GBM cannot be predicted, we performed a measure of treatment compliance before proceeding to an efficacy trial. METHODS: Feasibility study in 12 Bev naïve recurrent GBM patients. Bev was administered in standard doses biweekly. The primary objective was to document compliance with MAD in at least 60% of the patients (7/12) at least 80% of the time at 12 weeks. Secondary objectives included adverse events, tumor response, PFS, OS. Monitoring of MAD biologic effects included serum glucose and urine ketones daily and serum B-hydroxybutyrate biweekly. Compliance was determined by review of daily food diary and ketone levels. RESULTS: 8/12 patients completed the trial at 12 weeks and all were compliant with diet and all achieved ketosis. One additional patient continues on study at 48 days. Three patients were removed from study: grade 3 hypertension related to Bev, grade 3 seizures related to tumor, tumor progression at 71 days. CONCLUSION: We document the feasibility of the MAD and Bev in recurrent GBM. We will present correlations of treatment outcome with serum levels of ketosis, glucose, insulin, amino acids and with tumor MCT4 expression and IDH1 mutation status.