Correlation of tumor topography and peritumoral edema of recurrent malignant gliomas with therapeutic response to intranasal administration of perillyl alcohol

Abstract

This study suggests that: (1) patients with recurrent gliomas with localization in the basal ganglia survive significantly longer than those with tumors at lobar localization; (2) presence of PTBE contributes to symptoms, likely to be implicated in the morbidity and invading potential of malignant gliomas. These findings support the theory that interaction between glioma cells at distinct brain microenvironment can influence the oncobiological behavior of glioma cells and ultimately to the prognosis.

Perillyl Alcohol for the Treatment of Temozolomide-Resistant Gliomas

“…Systemic and neurologic toxicity have been minimal, with no gastrointestinal or hematologic side effects noted. Radiographic regression has been seen in 36% of patients, with 48.3% of the recurrent GBM patients achieving a 6-month progression-free survival, similar to the bevacizumab (Avastin) data for recurrent GBM (6). Additional advances using an intranasal atomizer (Via Nase; Kurve Technologies) would optimize the efficiency of POH delivery, because the nozzle is capable of delivering particles based on formulation and size (controlled particle dispersion).…”

“…POH clinical trials by Da Fonseca and colleagues have been conducted using POH purchased from Sigma Chemicals and delivered via facemask, at a total dosage of 440 mg/d (given 4 times a day; ref. 6). This dosage in humans (6.3 mg/kg, assuming a 70 kg patient), is approximately 3 times greater than the amount of drug administered to the animals in our study (i.e., 0.76 and 1.9 mg/kg).…”

“…The reason that such relatively high concentrations of drug are administered may be the results of inefficient intranasal drug delivery via the Continuous Positive Airway Pressure face mask. However, this route is still more efficient than oral delivery, where up to 13.8 grams is given orally (6). Indeed, Da Fonseca and colleagues have shown that POH can be safely delivered intranasally on a long-term basis, with documented radiographic reduction in tumor size (11).…”

“…Intranasal POH has been very well tolerated, with minimal systemic side effects, and only local irritation to the nasal mucosa. Younger patients with secondary GBMs responded best to POH treatment (6). Surprisingly, patients with deep midline or subcortical GBMs had a better response than cortical GBMs (6).…”

“…Younger patients with secondary GBMs responded best to POH treatment (6). Surprisingly, patients with deep midline or subcortical GBMs had a better response than cortical GBMs (6). This is particularly cogent, as patients with cortical GBMs are often surgically resectable, whereas the subcortical and deep GBMs are much more limited in surgical options and depend on adjunctive therapy for treatment.…”