ERGO: A pilot study of ketogenic diet in recurrent glioblastoma

Abstract

Limiting dietary carbohydrates inhibits glioma growth in preclinical models. Therefore, the ERGO trial (NCT00575146) examined feasibility of a ketogenic diet in 20 patients with recurrent glioblastoma. Patients were put on a low-carbohydrate, ketogenic diet containing plant oils. Feasibility was the primary endpoint, secondary endpoints included the percentage of patients reaching urinary ketosis, progression-free survival (PFS) and overall survival. The effects of a ketogenic diet alone or in combination with bevacizumab was also explored in an orthotopic U87MG glioblastoma model in nude mice. Three patients (15%) discontinued the diet for poor tolerability. No serious adverse events attributed to the diet were observed. Urine ketosis was achieved at least once in 12 of 13 (92%) evaluable patients. One patient achieved a minor response and two patients had stable disease after 6 weeks. Median PFS of all patients was 5 (range, 3–13) weeks, median survival from enrollment was 32 weeks. The trial allowed to continue the diet beyond progression. Six of 7 (86%) patients treated with bevacizumab and diet experienced an objective response, and median PFS on bevacizumab was 20.1 (range, 12–124) weeks, for a PFS at 6 months of 43%. In the mouse glioma model, ketogenic diet alone had no effect on median survival, but increased that of bevacizumab-treated mice from 52 to 58 days (p<0.05). In conclusion, a ketogenic diet is feasible and safe but probably has no significant clinical activity when used as single agent in recurrent glioma. Further clinical trials are necessary to clarify whether calorie restriction or the combination with other therapeutic modalities, such as radiotherapy or anti-angiogenic treatments, could enhance the efficacy of the ketogenic diet.

A Supplemented High-Fat Low-Carbohydrate Diet for the Treatment of Glioblastoma

“…Several case reports describe the applicability (20) and combinatorial safety of KD and RKD with current SOC therapies (17), with some patients experiencing stable disease on the diet and others experiencing unable to maintain (19). In 2014, the first phase one clinical trial assessing the safety of the KD on recurrent glioblastoma determined that the diet is safe and feasible, warranting other trials to explore the combinatorial potential of the KD with cytotoxic treatments (18). The KD in the context of cancer is promising, however patient populations are diverse, as are their dietary needs (21), creating a demand for alternative dietary interventions for tumor management (22).…”

“…14, 15) in the treatment of brain cancer by diminishing tumor growth and increasing animal survival. Clinical reports (5), case reports (16,17), and pilot trials (18)(19)(20) have demonstrated that the KD is safe, has low toxicity, and is applicable to cancer patients.…”

Systematic Review of the Use of Ketones in the Management of Acute and Chronic Neurological Disorders

“…He was commenced on the oral diet and maintained it for 12 weeks, however clinical and radiological assessment at this time point revealed tumour progression and he subsequently withdrew from the study. Rieger et al prospectively investigated 20 adult patients with recurrent glioblastoma to assess the feasibility of a very-low carbohydrate diet as a potential treatment modality in this group, over a 16-week period [32]. After 2-3 weeks, three patients (15%) discontinued the diet due to the impact on their quality of life.…”

Treatment of Rectal Cancer with the Paleolithic Ketogenic Diet: A 24-months Follow-up

“…This study was, however, also limited in follow-up duration, so the contribution of diet versus the radiation treatment cannot be discerned. In a study with patients with recurrent glioblastoma no significant clinical effect was seen [12] while in a retrospective study with brain cancer patients, survival benefit was uncertain [13].…”