ERGO2: A prospective randomized trial of calorie restricted ketogenic diet and fasting in addition to re-irradiation for malignant glioma.

Abstract Purpose XXXX is the first randomized clinical trial of calorically restricted ketogenic diet (KD) and intermittent fasting (KD-IF) in addition to re-irradiation for recurrent malignant gliomas. Methods 50 Patients were randomized 1:1 to re-irradiation combined with either calorically unrestricted 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. Primary endpoint was progression-free survival (PFS) rate at 6 months (PFS6). Secondary endpoints were PFS, local PFS, overall survival (OS), frequency of epileptic seizures, rate of ketosis and quality of life. Results 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. PFS6 was not significantly different between the two groups (KD-IF: 20%, SD: 16%). Similarly, no difference in PFS, local PFS6 and OS was observable. Explorative analysis revealed that patients of the KD-IF group who had a glucose of less than the median (83.5 mg/dl) on day 6 had a significantly longer PFS and OS compared to those above the median (p Conclusion KD-IF is feasible and effective in inducing ketosis in heavily pretreated patients with recurrent glioma. However, the short schedule reported here failed to increase the efficacy of re-irradiation.