Dataset Information

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.

SUBMITTER: van der Louw EJTM

PROVIDER: S-EPMC6589986 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

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

van der Louw Elles J T M EJTM Olieman Joanne F JF van den Bemt Patricia M L A PMLA Bromberg Jacoline E C JEC Oomen-de Hoop Esther E Neuteboom Rinze F RF Catsman-Berrevoets Coriene E CE Vincent Arnaud J P E AJPE

Therapeutic advances in medical oncology 20190621

<h4>Background</h4>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.<h4>Methods</h4>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-tri ...[more]

PMID: 31258628

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Project description:Abstract INTRODUCTION There is abundant interest in the potential therapeutic and supportive role of a ketogenic diet (KD) for glioblastoma patients. We conducted a single-arm phase 1 trial to assess the safety and feasibility of KD plus standard-of-care (SOC) in glioblastoma patients (NCT03451799). METHODS Adults within 3 months of diagnosis participated in a 16-week intervention of a classic 3:1 KD (grams fat : grams carbohydrate + protein) with dietitian support. Blood glucose and ketone levels were assessed twice daily (Keto-Mojo), with remote monitoring of daily weight and activity (Fitbit). The primary objective was to assess safety (weight stability, CTCAE) and feasibility (maintaining ketosis > 0.3mM for > 50% of study period). Secondary objectives included assessments of progression-free survival (PFS), overall survival (OS), health-related quality of life (HRQOL), and cognition (MoCA). RESULTS From 04/2018-02/2021, 14 patients were evaluable: female:male, 8:6, median age 55 years, KPS 80, BMI 24.5. MGMT promoter methylation: 6 present, 7 absent, 1 indeterminate. Adherence to KD was high, with all patients maintaining ketosis ( > 0.3mM) > 50% and 11 patients maintaining ketosis > 85% of study days. Adverse events (> Grade 2) potentially attributable to KD: appetite loss (Grade 2: 2); fatigue (Grade 2: 5); flu-like symptoms (Grade 2: 1); constipation (Grade 2: 5, Grade 3: 1). No patients were removed from study for safety reasons. HRQOL was stable, with improvements in role function (not statistically significant). MoCA score improved in 10/14 patients. Median PFS and OS from KD initiation were 11.7 and 29.1 months, respectively. CONCLUSION Our findings suggest that a supervised KD plus SOC is safe and feasible in glioblastoma patients. KD was well-tolerated with encouraging trends in HRQOL and cognition. PFS and OS in this small trial compare favorably to historical control. A multicenter phase 2 trial powered to assess efficacy is planned.

Project description:PURPOSE:Even with an optimal treatment protocol, the median survival of glioblastoma (GB) patients is only 12-15 months. Hence, there is need for novel effective therapies that improve survival outcomes. Recent evidence suggests an important role for connexin (Cx) proteins (especially Cx43) in the microenvironment of malignant glioma. Cx43-mediated gap junctional communication has been observed between tumor cells, between astrocytes and between tumor cells and astrocytes. Therefore, gap junction directed therapy using a pharmacological suppressor or modulator, such as tonabersat, could be a promising target in the treatment of GB. In this preclinical study, we evaluated the possible therapeutic potential of tonabersat in the F98 model. PROCEDURES:Female Fischer rats were inoculated with ± 25.000 F98 tumor cells in the right frontal lobe. Eight days post-inoculation contrast-enhanced T1-weighted (CE-T1w) magnetic resonance (MR) images were acquired to confirm tumor growth in the brain. After tumor confirmation, rats were randomized into a Control Group, a Connexin Modulation Group (CM), a Standard Medical Treatment Group (ST), and a Standard Medical Treatment with adjuvant Connexin Modulation Group (STCM). To evaluate therapy response, T2-weighted (T2w) and CE-T1w sequences were acquired at several time points. Tumor volume analysis was performed on CE-T1w images and statistical analysis was performed using a linear mixed model. RESULTS:Significant differences in estimated geometric mean tumor volumes were found between the ST Group and the Control Group and also between the STCM Group and the Control Group. In addition, significant differences in estimated geometric mean tumor volumes between the ST Group and the STCM Group were demonstrated. No significant differences in estimated geometric mean tumor volumes were found between the Control Group and the CM Group. CONCLUSION:Our results demonstrate a therapeutic potential of tonabersat for the treatment of GB when used in combination with radiotherapy and temozolomide chemotherapy.

Dataset Information

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

Background

Methods

Results

Conclusion

Clinical trial registration

Publications

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

Similar Datasets

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