We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
A Phase I clinical trial of dose-escalated metabolic therapy combined with concomitant radiation therapy in high-grade glioma.
- Authors
Porper, Keren; Shpatz, Yael; Plotkin, Luba; Pechthold, Ronit Goldman; Talianski, Alisa; Champ, Colin E.; Furman, Orit; Shimoni-Sebag, Ariel; Symon, Zvi; Amit, Uri; Hemi, Rina; Kanety, Hannah; Mardor, Yael; Cohen, Zvi R.; Jan, Elisheva; Genssin, Hili; Anikster, Yair; Zach, Leor; Lawrence, Yaacov R.
- Abstract
Background: Animal brain-tumor models have demonstrated a synergistic interaction between radiation therapy and a ketogenic diet (KD). Metformin has in-vitro anti-cancer activity, through AMPK activation and mTOR inhibition. We hypothesized that the metabolic stress induced by a KD combined with metformin would enhance radiation's efficacy. We sought to assess the tolerability and feasibility of this approach. Methods: A single-institution phase I clinical trial. Radiotherapy was either 60 or 35 Gy over 6 or 2 weeks, for newly diagnosed and recurrent gliomas, respectively. The dietary intervention consisted of a Modified Atkins Diet (ModAD) supplemented with medium chain triglycerides (MCT). There were three cohorts: Dietary intervention alone, and dietary intervention combined with low-dose or high-dose metformin; all patients received radiotherapy. Factors associated with blood ketone levels were investigated using a mixed-model analysis. Results: A total of 13 patients were accrued, median age 61 years, of whom six had newly diagnosed and seven with recurrent disease. All completed radiation therapy; five patients stopped the metabolic intervention early. Metformin 850 mg three-times daily was poorly tolerated. There were no serious adverse events. Ketone levels were associated with dietary factors (ketogenic ratio, p < 0.001), use of metformin (p = 0. 02) and low insulin levels (p = 0.002). Median progression free survival was ten and four months for newly diagnosed and recurrent disease, respectively. Conclusions: The intervention was well tolerated. Higher serum ketone levels were associated with both dietary intake and metformin use. The recommended phase II dose is eight weeks of a ModAD combined with 850 mg metformin twice daily.
- Subjects
BRAIN tumors; RADIOTHERAPY; PROGRESSION-free survival; FOOD consumption; CLINICAL trials; GLIOMAS
- Publication
Journal of Neuro-Oncology, 2021, Vol 153, Issue 3, p487
- ISSN
0167-594X
- Publication type
Article
- DOI
10.1007/s11060-021-03786-8