Efficacy of monoterpene perillyl alcohol upon survival rate of patients with recurrent glioblastoma
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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.
Patients and methods
It was included 89 adults with recurrent GBM receiving daily intranasal administration of 440 mg 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 11.2 months, longer (log rank test, P = 0.0366) than primary GBM (5.9 months). 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 4 years.
KeywordsGlioblastoma Perillyl alcohol Terpene Intranasal administration Tumor topography
This study was supported by grants from FAPERJ (Fundação de Amparo a Pesquisa do Rio de Janeiro, number: E-26/111.425/2008) and CNPq (Brazilian Research Council number: 470441/2008-9). We thank Marcela d’Allincourt Salazar from the Biochemistry and Cancer Biology program of The University of Toledo, Ohio, USA for general discussion and critical reading of the manuscript and the pathologist Janaina Nagel for histological analysis and Silvana da Silva Souza for technical assistance with the intranasal formulation of perillyl alcohol and Adriano Arnobio for the statistical analysis.
Conflict of interest statement
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