Question explored with the scientific record
Have any randomized trials tested metabolic therapy or drug repurposing against standard temozolomide treatment in glioblastoma?
No randomized trial of metabolic therapy or drug repurposing against standard temozolomide for glioblastoma was found in the retrieved evidence.
The evidence you provided covers temozolomide's efficacy, dosing schedules, and combinations with radiotherapy or tumor-treating fields [1][2][3][4][5]. It also includes a systematic review of ketogenic metabolic therapy (KMT) as an adjuvant to standard care, but that review explicitly states the studies were small, heterogeneous, and lacked controlled designs — no randomized trial comparing KMT to standard temozolomide was identified [6]. A narrative review on ketogenic diet for glioblastoma likewise concludes that clinical trial evidence is insufficient [7].
For drug repurposing, the retrieval includes an in vitro study of mebendazole and fenbendazole in canine glioma cells [8] and a single-arm, open-label Phase II study of apatinib plus temozolomide in recurrent glioblastoma [9]. Neither is a randomized trial against standard temozolomide. The apatinib study itself calls for randomized trials [9].
The retrieval did not surface any randomized trial that tests metabolic therapy (such as ketogenic diet) or a repurposed drug (such as mebendazole, metformin, or disulfiram) head-to-head against standard temozolomide-based treatment for glioblastoma. The evidence that exists is limited to small feasibility studies and preclinical work, none of which meet the standard of a randomized controlled comparison.
My call: the evidence does not show that any randomized trial has tested metabolic therapy or drug repurposing against standard temozolomide for glioblastoma. Confidence: low — the retrieval may have missed such trials, but within what was found, none exist.
Sources used 9
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Efficacy of concomitant and adjuvant temozolomide in glioblastoma treatment. A multicentre randomized study
This multicenter randomized study evaluates the efficacy and safety of concomitant and adjuvant temozolomide combined with radiotherapy in patients with newly diagnosed glioblastoma multiforme, demonstrating a significant improvement in overall survival compared to radiotherapy …
DOI: 10.5114/ninp.2013.34398 -
Radiotherapy (RT) and concomitant and adjuvant temozolomide (TMZ) versus radiotherapy alone for newly diagnosed glioblastoma (GBM): Overall results and recursive partitioning analysis (RPA) of a phase III randomized trial of the EORTC brain tumor and radiotherapy groups and the NCIC clinical trial group
This study evaluates the efficacy of concomitant and adjuvant temozolomide combined with radiotherapy compared to radiotherapy alone in improving overall survival for patients with newly diagnosed glioblastoma.
DOI: 10.1016/s0360-3016(04)01138-1 -
Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma
This randomized clinical trial evaluates the efficacy and safety of tumor-treating fields (TTFields) combined with temozolomide maintenance treatment after chemoradiation therapy in patients with glioblastoma, demonstrating significant improvements in progression-free and overal…
DOI: 10.1001/jama.2015.16669 -
Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial
This study presents a five-year analysis of the EORTC-NCIC trial, demonstrating that the combination of radiotherapy with concomitant and adjuvant temozolomide significantly improves overall survival in glioblastoma patients compared to radiotherapy alone.
DOI: 10.1016/S1470-2045(09)70025-7 -
Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma
This study demonstrates that the addition of temozolomide to radiotherapy for newly diagnosed glioblastoma significantly improves overall survival with minimal additional toxicity.
DOI: 10.1056/NEJMoa043330 -
Efficacy of ketogenic metabolic therapy as an adjuvant to the current standard of care in the treatment of glioblastoma: A systematic review of clinical trials
A PRISMA-guided systematic review assessing ketogenic metabolic therapy (KMT) as an adjuvant to standard therapy for glioblastoma, finding feasibility and safety across small, heterogeneous studies but no definitive efficacy conclusions due to lack of standardized protocols and …
DOI: 10.1007/s12032-025-03165-7 -
Ketogenic Diet as a Novel Treatment for Glioblastoma
A narrative review argues that ketogenic diet with caloric restriction may improve glioblastoma therapy by exploiting the Warburg effect, but concludes that clinical trial evidence is insufficient.
DOI: 10.14744/ejmo.2017.29591 -
In vitro anti‐tubulin effects of mebendazole and fenbendazole on canine glioma cells
Mebendazole and fenbendazole show low-micromolar in vitro cytotoxicity against three canine glioma cell lines and disrupt tubulin, with no significant effect on primary canine fibroblasts at IC50.
DOI: 10.1111/vco.12288 -
<p>Apatinib Plus Temozolomide for Recurrent Glioblastoma: An Uncontrolled, Open-Label Study</p>
A single-arm, open-label Phase II study evaluating apatinib plus dose-dense temozolomide in 20 adults with recurrent glioblastoma, showing 45% objective response, 90% disease control, median progression-free survival of 6 months, median overall survival of 9 months, with managea…
DOI: 10.2147/OTT.S226804