Background: Glioblastoma (GBM) is a highly aggressive primary brain cancer that is difficult to treat. The current standard of care consists of surgery, followed by radiation and chemotherapy with the alkylating agent temozolomide (TMZ) (1). It has been hypothesized that ketogenic diet (KD) might represent 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. This study aimed to evaluate the therapeutic efficacy of intranasal POH administered in combination with a ketogenic diet (KD) program for the treatment of patients with recurrent glioblastoma.
Methods: Thirty-two patients, treated with intranasal POH (55 mg, four times daily), were divided into two groups - KD (n=17) or standard diet (n=15). The nutritional status and anthropometric parameters of patients were measured. Patients maintained the combination treatments for three months. Neurological examination and magnetic resonance imaging were used to monitor disease progression. In the KD patient, strict compliance with the KD was confirmed by measuring the levels of ketone bodies in the urine at three times a week.
Results: The effect of ketogenic diet in combination with intranasal POH was significant in the reduction of tumor mass (p = 0.035; 33.8%) compared to the control group, as demonstrated by magnetic resonance. There was no significant difference in glucose levels at baseline and after 90 days between groups. However, statistical significance was observed between the levels of total cholesterol (p = 0.003), LDL-c (p = 0.0002) and triglycerides (p = 0.004) in treated group only. The ketogenic diet combined with intranasal POH had a favorable response in reducing tumor growth.
Conclusion: Altogether, the results suggest that KD associated with intranasal POH may represent a viable option as an adjunct therapy for recurrent GBM.