Preliminary results from a phase I/II study of perillyl alcohol intranasal administration in adults with recurrent malignant gliomas

Surg Neurol. 2008 Sep;70(3):259-66; discussion 266-7. doi: 10.1016/j.surneu.2007.07.040. Epub 2008 Mar 4.


Background: Activation of the p21-ras signaling pathway from aberrantly expressed receptors promotes the growth of malignant human astrocytomas. Perillyl alcohol has shown to have both chemopreventive and chemotherapeutic activities in preclinical studies. The underlying action mechanism(s) of POH has yet to be delineated but may involve effects on the TGF-beta and/or the Ras signaling pathways. The intranasal delivery allows drugs that do not cross the BBB to enter the CNS; moreover, it eliminates the need for systemic delivery, thereby reducing unwanted systemic side effects.

Methods: We are conducting a phase I/II study to evaluate the antitumoral activity of POH intranasal delivery in a 4x daily schedule in patients with recurrent MG. The objective was to determine PFS at 6 months and the safety for POH in adult patients who failed conventional treatment. Assessments were performed every 27 days. Thirty-seven patients with progressive disease after prior surgery, radiotherapy, and at least temozolomide-based chemotherapy were enrolled, 29 of whom had GBM, 5 who had anaplastic astrocytoma, and 3 had AO.

Results: One patient (3.4%) with GBM and 1 patient (33.3%) with AO achieved partial response; 13 patients (44.8%) with GBM, 3 patients (60%) with AA, and 1 (33.3%) with AO achieved stable disease; 15 (51.7%) patients with GBM, 2 (40%) patients with AA, and 1 (33.3%) with AO showed progressive disease. Progression-free survival (partial response and stable disease) was 48.2% for patients with GBM, 60% for patients with AA, and 66.6% for patients with AO.

Conclusions: There were no toxicity events. Perillyl alcohol is well tolerated and regression of tumor size in some patients is suggestive of antitumor activity. This work discusses POH intranasal delivery as a potential adjuvant therapeutic strategy for patients with malignant gliomas.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal*
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / physiology
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / physiopathology
  • Dacarbazine / administration & dosage
  • Dacarbazine / analogs & derivatives
  • Disease Progression
  • Drug Administration Schedule
  • Enzyme Inhibitors / administration & dosage
  • Female
  • Glioma / drug therapy*
  • Glioma / metabolism
  • Glioma / physiopathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Monoterpenes / administration & dosage*
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / physiopathology
  • Oncogene Protein p21(ras) / drug effects
  • Oncogene Protein p21(ras) / genetics
  • Oncogene Protein p21(ras) / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Survival Rate
  • Temozolomide
  • Transforming Growth Factor beta / drug effects
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Treatment Outcome


  • Antineoplastic Agents
  • Antineoplastic Agents, Alkylating
  • Enzyme Inhibitors
  • Monoterpenes
  • Transforming Growth Factor beta
  • perillyl alcohol
  • Dacarbazine
  • Oncogene Protein p21(ras)
  • Temozolomide