Glioblastoma (GB) is the most malignant brain cancer, with few patients surviving beyond 2 years despite treatment including surgical resection, radiation, chemotherapy and new experimental therapies. Improvements in survival require the design of novel therapies that take advantage of phenotypic traits common in tumor cells. One such trait is aberrant metabolism - tumors rely heavily on glucose and glutamine as energy sources and are unable to use other sources of energy. We and others have suggested the exploitation of this through the use of the ketogenic diet (KD), a high fat, low carbohydrate and protein diet (4:1 fat:protein plus carbohydrate) that causes the body to shift metabolically from glucose to ketones as the primary source of energy. In addition to reducing available glucose, in vitro and in vivo preclinical studies have shown that increasing ketones appears to have additional anti-tumor effects, even in the presence of normal glucose levels. We and others have shown that the KD improves survival in mouse models of malignant brain tumors, and we have shown that it potentiates the effects of radiation and chemotherapy in vitro and in vivo. Anecdotal evidence and published case reports suggest that it may also have efficacy in human glioma patients, thus warranting further investigation in a clinical setting.
Here, we report results to date from our ongoing, phase I/II single-arm clinical trial of this intervention (clinicaltrials.gov NCT02046187). Patients are eligible to enroll if they have newly diagnosed GB and at least a subtotal surgical resection. The KD is used in addition to standard care (radiation and temozolomide). It is already known to be safe and effective in the treatment of refractory epilepsy. Patients follow a 4:1 ketogenic diet during concurrent radiation and chemotherapy; they then change to a more moderate 1:1 diet during adjuvant chemotherapy. Blood glucose and ketone measurements are recorded daily, with target levels of glucose at ∼70ml/dl and ketones at ∼4mmol/l.
To date, our preliminary study suggests that the KD is generally well tolerated and steroid use does not preclude the patient's ability to reduce glucose levels below 80ml/ml. Overall health and therapy-related quality of life measurements decline from baseline to the end of RT as is typical for patients undergoing radiation therapy, but appears to recover back to baseline over time. This suggests that following the ketogenic diet probably does not adversely affect long-term quality of life. Additional patient followup data will be presented.
Citation Format: Leonora Renda, Norissa Honea, Christopher Dardis, Lynn S. Ashby, Adrienne C. Scheck. Clinical effects of a ketogenic diet on brain tumor patients: tumor growth and quality of life. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT213. doi:10.1158/1538-7445.AM2015-CT213