title: 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.
authors.affiliation: Dr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, D-60528 Frankfurt, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Rieger
authors.affiliation: Dr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, D-60528 Frankfurt, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Bähr
authors.affiliation: Dr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, D-60528 Frankfurt, Germany.
authors.forename: Gabriele D
authors.initials: GD
authors.lastname: Maurer
authors.affiliation: Institute of Neuroradiology, University Hospital Frankfurt, D-60528 Frankfurt, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Hattingen
authors.affiliation: Department for Neurosurgery, University Hospital Frankfurt, D-60528 Frankfurt, Germany.
authors.forename: Kea
authors.initials: K
authors.lastname: Franz
authors.affiliation: Dr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, D-60528 Frankfurt, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Brucker
authors.affiliation: Institute of Physiology and Pathophysiology, Johannes Gutenberg-University, D-55099 Mainz, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Walenta
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital of Würzburg, D-97080 Würzburg, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kämmerer
authors.affiliation: Tavarlin AG, D-64293 Darmstadt, Germany.
authors.forename: Johannes F
authors.initials: JF
authors.lastname: Coy
authors.affiliation: Department of Neurology, University Hospital Tübingen, D-72076 Tübingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
authors.affiliation: Dr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, D-60528 Frankfurt, Germany.
authors.forename: Joachim P
authors.initials: JP
authors.lastname: Steinbach
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068258:Bevacizumab; D003131:Combined Modality Therapy; D055423:Diet, Ketogenic / Q000009:adverse effects*; D005260:Female; D005909:Glioblastoma / Q000178:diet therapy* / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007662:Ketosis / Q000652:urine; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000628:therapy*; D009374:Neoplasms, Experimental; D010865:Pilot Projects; D011788:Quality of Life; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068258:Bevacizumab
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