New therapeutic approach for brain tumors: Intranasal administration of Ras inhibitor perillyl alcohol.

Abstract

2098 Background: Historically, recurrent glioblastoma (GBM) has a median survival of three to six months. Since active Ras contribute to malignant phenotype of these brain tumors we are conducting a phase I/II study to evaluate the antitumoral activity of intranasal administration of a Ras inhibitor, perillyl alcohol (POH), in a 4× daily schedule in patients with recurrent malignant gliomas. 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 group. Results: Six month free survival (stable disease) was 48.3% for POH-treated patients with significant (p = 0.0001) survival advantage compared with historical control untreated group. Median survival rate of secondary GBM was 11.2 months, longer (p = 0.0002) than primary GBM (5.9 months). Age adjustment multivariate analysis showed significant difference (p = 0.0002) in the survival rate between primary and secondary GBM. Patients with tumors localized in deep regions (thalamus, basal ganglia) survived longer (p = 0.0083) than those with tumors in lobar regions. Radiographic improvement and reduction of corticosteroid dosage (36 %) further associated with a delay towards progression. Conclusions: Intranasal administration of POH increased the overall survival of patients with recurrent GBM in comparison with historical controls, but especially patients with secondary GBM and those with tumor localized in deep regions of the brain without clinical evidence of side effects for over a year. No significant financial relationships to disclose.