Efficacy of monoterpene perillyl alcohol upon survival rate of patients with recurrent glioblastoma

Abstract

The monoterpene perillyl alcohol (POH) a Ras inhibitor with potential capacity to arrest gliomagenesis is being used in a phase I/II clinical trial in adults with recurrent malignant glioma. The present study aimed to investigate the efficacy of intranasal administration of monoterpene POH upon survival rate of patients with recurrent glioblastoma (GBM) in comparison with historical control group of GBM patients. It was included 89 adults with recurrent GBM receiving daily intranasal administration of 440mg POH and 52 matched GBM patients as historical control untreated group only with supportive treatment. Patients with recurrent primary GBM treated with POH survived significantly longer (log rank test, P<0.0001) than untreated group. Patients with recurrent primary GBM in deep location survived significantly longer than with lobar location (log rank test, P<0.0001). Median survival rate of secondary GBM was 11.2months, longer (log rank test, P=0.0366) than primary GBM (5.9months). Radiographic improvement and reduction of corticosteroid dosage (36%) further associated with a delay towards progression. Intranasal administration of POH increased the overall survival of patients with recurrent GBM in comparison with historical untreated controls, but especially patients with secondary GBM and primary GBM with tumor localized in deep regions of the brain. The side effects of POH treatment were almost nonexistent, even in patients treated for over 4years.