Case of Advanced Recurrent Glioblastoma Successfully Treated with Monoterpene Perillyl Alcohol by Intranasal Administration

Abstract

We report a case of recurrent glioblastoma (GBM) successfully treated with the Ras inhibitor monoterpene perillyl alcohol by intranasal administration. A 37-years-old white woman had been previously submitted to three neurosurgical procedures, in June 2000 for radical tumor excision of grade II astrocytoma; in July 2003 for first recurrence of type IV glioma and in August 2004 for GBM recurrence. After last surgery, patient started a new cycle of chemotherapy but was refractory to treatment, presented clinical adverse effects and resonance image scan showed no reduction of tumoral lesion. Patient was then considered out of therapeutic possibilities and indicated for supportive treatment. On March 2005 patient joined Phase I/II clinical trial for assess the efficacy of the monoterpene POH, a Ras inhibitor. POH was administered by intranasal route four times a day (268 mg daily) as single chemotherapy agent. Image scans performed 3 and 5 years later revealed marked reduction of enhancing lesion. This illustrative case demonstrates that intranasal administration of the monoterpene POH as a single agent was an effective therapeutic strategy capable to sustain long-term regression of recurrent glioma without clinical and laboratory toxicity

Influence of GSTM1 and GSTT1 polymorphisms on the survival rate of patients with malignant glioma under perillyl alcohol-based therapy

“…This is consistent with previous findings that patients with deep gray matter glioma may survive longer than those with tumors in a lobar location (Ramnarayan et al, 2007). The present results partly explain previous data (da Fonseca et al, 2011) showing that tumor location and polymorphisms of GSTM1 and GSTT1 may exert additional influence on the survival of patients with malignant gliomas. It is important to conduct larger studies to confirm whether GST genotypes that encode high-activity enzymes influence POH detoxification, which may be an independent predictor of outcome and response to POH-based therapy.…”

Intranasal drug delivery: opportunities and toxicologic challenges during drug development

“…The main advantage of the IN route is the chance of reduced side effects in other organ systems [146,154]. Different approaches showed that chemotherapeutic agents for treating brain tumours such as perillyl alcohol, methotrexate and telomerase inhibitors can be delivered via the nasal route and are effective alternative strategies [155][156][157][158][159][160].…”

Natural Monoterpenes: Much More than Only a Scent

“…One reason is that these monoterpenes, when administered orally, are characterized by holding relatively insufficient ‘druglikeness’, This comes about because these metabolites are poorly soluble in water due to their lipophilic nature, hence, issues arise in their transportation within the blood system. However, monoterpenes can easily be administered intranasally, as has been proven clinically useful in the treatment of recurrent glioblastoma . In this review, particular attention will be paid to the influence of monoterpene structure on their physicochemical properties and pharmacological activity.…”