CBMT-20. A KETOGENIC PILL FOR GLIOBLASTOMA

INTRODUCTION: While the KD holds promise as a therapeutic option for brain cancer patients, stringency of the diet impacts compliance. We have previously demonstrated that a high fat/low carbohydrate diet, similar to the Ketogenic Diet [KD], can reduce tumor progression and enhance survival in an orthotopic xenograft model. However, while this diet is less restrictive than the classic KD it still involves significant changes to a patient’s diet. Two of the primary physiological changes that occur when on the KD are a reduction in glucose and an increase in ketone bodies. These physiological changes are mimicked by providing ketone esters [KE] in the diet, and we [AMP, DPD], have recently shown that ketone esters can reduce glucose, elevate ketone bodies and enhance survival in a metastatic cancer model. HYPOTHESIS: We hypothesize that KE [1,3 butanediol acetoacetate diester] will reduce glucose, elevate ketones, reduce tumor progression and enhance survival in an orthotopic xenograft GBM model using a PDX model. APPROACH: NON/SCID animals implanted with patient-derived GBM cells were fed a standard diet [SD], or SD + KE [20%] till they reached endpoint. Body weight, plasma glucose, and ketones were measured weekly and overall survival assessed. RESULTS: While the KE is bitter and can have poor compliance, we found that supplementing with 1% Stevia increased palatability based on food consumption and body weight. Comparing to SD, KE supplemented diet reduced plasma glucose (145.5 ± 5.3 vs 121.7 ± 5.7), increased ketone bodies [ß-hydroxybutarate, 0.7 ± 0.15 vs.1.3 ± 0.1] and enhanced median survival [47 ± 6.2 vs 60.8 ± 1.9, days]. CONCLUSION: Ketone esters can be effectively delivered orally together with a standard diet, and produce similar physiological changes [reduction in glucose and elevation in ketones] and enhance survival as the more restrictive KD in NON/SCID animals.