OS6.5 ERGO2: A prospective randomized trial of a 9-day schedule of calorically restricted ketogenic diet and fasting or standard diet in addition to re-irradiation for malignant glioma

Abstract

Abstract BACKGROUND Ketogenic diet (KD) and fasting have anticancer effects in tumor models, possibly due to a differential stress response with sensitization of tumor cells and protection of normal tissue. We therefore set up ERGO2 (NCT01754350), the first randomized clinical trial of calorically-restricted KD and intermittent fasting (KD-IF) in addition to re-irradiation for recurrent malignant gliomas. MATERIAL AND METHODS Patients were randomized 1:1 to re-irradiation combined with either calorically unrestricted diet (standard diet, SD) or KD-IF. The KD-IF schedule included 3 days of KD (21–23 kcal/kg/d), followed by 3 days of fasting and again 3 days of KD. The primary endpoint was progression-free survival (PFS) rate at 6 months (PFS6). Secondary endpoints were PFS, local control, overall survival (OS), frequency of epileptic seizures, rate of ketosis and quality of life. RESULTS 50 patients were included. Four patients quit the trial before treatment and three patients stopped KD-IF prematurely. Of the 20 patients who completed KD-IF, 17 patients developed ketosis at day 6, and glucose levels declined significantly. KD-IF was well-tolerated with a modest weight loss of -2.1±1.8 kg. No severe adverse events attributable to the diet occurred. There was no difference in PFS6 between the two groups (KD-IF: 20%, SD: 16%). Similarly, no difference in PFS, local PFS6 and OS were observable. Explorative analysis revealed that among patients of the KD-IF group, those who achieved ketosis of at least 1.5 mmol/l had significantly longer PFS compared to those with lesser or no ketosis. CONCLUSION KD-IF is feasible and effective in inducing ketosis in heavily pretreated patients with recurrent glioblastoma. However, the short schedule reported here failed to increase the efficacy of re-irradiation.