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Efficacy of a ketogenic diet with concomitant intranasal perillyl alcohol as a novel strategy for the therapy of recurrent glioblastoma

  • Authors:
    • Juliana Guimarães Santos
    • Wanise Maria Souza Da Cruz
    • Axel H. Schönthal
    • Marcela D'alincourt Salazar
    • Cristina Asvolinsque Pantaleão Fontes
    • Thereza Quirico‑Santos
    • Clovis Orlando Da Fonseca

  • View Affiliations

  • Published online on: November 8, 2017     https://doi.org/10.3892/ol.2017.7362
  • Pages: 1263-1270
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Abstract

It has been hypothesized that persistent ketotic hypoglycemia represents a potential therapeutic strategy against high‑grade gliomas. Perillyl alcohol (POH) is a non‑toxic, naturally‑occurring, hydroxylated monoterpene that exhibits cytotoxicity against temozolomide‑resistant glioma cells, regardless of O6‑methylguanine‑methyltransferase promoter methylation status. The present study aimed to evaluate the toxicity and therapeutic efficacy of intranasal POH when administered in combination with a ketogenic diet (KD) program for the treatment of patients with recurrent glioblastoma. The 32 enrolled patients were divided into two groups, KD or standard diet, with intranasal POH treatment (n=17 and n=15, respectively). The nutritional status and anthropometric parameters of the patients were measured. Patients that adhered to the KD maintained a strict dietary regimen, in addition to receiving 55 mg POH four times daily, in an uninterrupted administration schedule for three months. Neurological examination and magnetic resonance imaging analysis were used to monitor disease progression. A total of 9/17 patients in the KD group survived and maintained compliance with the KD. After three months of well‑tolerated treatment, a partial response (PR) was observed for 77.8% (7/9) of the patients, stable disease (SD) in 11.1% (1/9) and 11.1% (1/9) presented with progressive disease (PD). Among the patients assigned to the standard diet group, the PR rate was 25% (2/8 patients), SD 25% (2/8) and PD 50% (4/8 patients). The patients assigned to the KD group presented with reduced serum lipid levels and decreased low‑density lipoprotein cholesterol levels. These results are encouraging and suggest that KD associated with intranasal POH may represent a viable option as an adjunct therapy for recurrent GBM.
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January-2018
Volume 15 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Santos JG, Da Cruz WS, Schönthal AH, Salazar MD, Fontes CP, Quirico‑Santos T and Da Fonseca CO: Efficacy of a ketogenic diet with concomitant intranasal perillyl alcohol as a novel strategy for the therapy of recurrent glioblastoma. Oncol Lett 15: 1263-1270, 2018.
APA
Santos, J.G., Da Cruz, W.S., Schönthal, A.H., Salazar, M.D., Fontes, C.P., Quirico‑Santos, T., & Da Fonseca, C.O. (2018). Efficacy of a ketogenic diet with concomitant intranasal perillyl alcohol as a novel strategy for the therapy of recurrent glioblastoma. Oncology Letters, 15, 1263-1270. https://doi.org/10.3892/ol.2017.7362
MLA
Santos, J. G., Da Cruz, W. S., Schönthal, A. H., Salazar, M. D., Fontes, C. P., Quirico‑Santos, T., Da Fonseca, C. O."Efficacy of a ketogenic diet with concomitant intranasal perillyl alcohol as a novel strategy for the therapy of recurrent glioblastoma". Oncology Letters 15.1 (2018): 1263-1270.
Chicago
Santos, J. G., Da Cruz, W. S., Schönthal, A. H., Salazar, M. D., Fontes, C. P., Quirico‑Santos, T., Da Fonseca, C. O."Efficacy of a ketogenic diet with concomitant intranasal perillyl alcohol as a novel strategy for the therapy of recurrent glioblastoma". Oncology Letters 15, no. 1 (2018): 1263-1270. https://doi.org/10.3892/ol.2017.7362