Ketogenic diet treatment as adjuvant to standard treatment of glioblastoma multiforme: a feasibility and safety study

Abstract

Background: High-grade glioma cells consume mainly glucose and cannot compensate for glucose restriction. Apoptosis may potentially occur under carbohydrate restriction by a ketogenic diet (KD). We explored the feasibility and safety of KD during standard treatment of chemoradiation in patients with glioblastoma multiforme.

Methods: A full liquid KD induced ketosis within 2 weeks before start of chemoradiation. After 6 weeks, the KD was modified with solid foods and medium-chain-triglyceride emulsions and used for an additional 6 weeks while maintaining ketosis. During the total study period (14 weeks), feasibility, safety, coping (both patient and partner), quality of life (QoL), neurological functioning and impairment were measured. Overall survival was analyzed with actuarial estimates.

Results: Eleven patients started the study protocol, nine reached ketosis and six (67%) completed the study. Severe adverse effects did not occur. The majority of coping scores ranged from 3 to 6 on a 10-point scale at all timepoints; QoL, neurological functioning, and impairment did not essentially change over time; overall survival ranged between 9.8 and 19.0 months.

Conclusion: KD was feasible and safe as an adjuvant to standard chemoradiation treatment of glioblastoma multiforme. A supportive partner and intensive counseling were essential for coping. Future research should identify possible beneficial effects on overall survival.

Clinical trial registration: Netherlands Trial Registry: NTR5167 (registration date 29-01-2015), http://www.trialregister.nl/trialreg/index.asp.

Keywords: adjuvant therapy; brain tumor; coping; metabolic therapy; side effects.

Figure 1.

Study flow chart. BMI, body mass index; CT, chemotherapy; KD, ketogenic diet; MCT, medium-chain triglycerides; RT, radiotherapy.

Figure 2.

Kaplan–Meier plot of overall survival stratified by time interval between diagnosis and death. n represents the number of patients at the start of the study; F represents the number of failures. Nine patients were included into phase A of the study: at 4 months and 8 months after diagnosis, nine had survived; at 12 months after diagnosis, six had survived; at 16 months after diagnosis three had survived; and at 20 months, all had died.