Pharmacokinetic investigation of increased efficacy against malignant gliomas of carboplatin combined with hyperbaric oxygenation

Abstract

The efficacy of intravenous administration of 400 mg carboplatin/m 2 body surface area over 60 minutes combined with hyperbaric oxygenation (HBO) therapy (0.2 MPa for 60 min) was investigated in 6 Japanese patients (aged 36-67 years) with malignant or brainstem gliomas. Plasma ultra-filtrate samples were analyzed by high-performance liquid chromatography to evaluate the relationship between efficacy and pharmacokinetics. Brain tumor response was evaluated by magnetic resonance imaging as a function of maximum plasma concentration, area under the curve, or mean residence time (MRT) for carboplatin. TheMRT for carboplatin in the complete or partial response group (mean ± standard deviation 4.3 ± 1.7 hrs; 6 courses in 3 patients) was significantly longer (p < 0.05) than that in the progressive disease group (2.4 ± 0.1 hrs; 3 courses in 3 patients), but maximum plasma concentration and area under the curve showed no differences. These results suggest that HBO therapy prolongs the biological residence time of carboplatin.MRT for carboplatinmay be useful for predicting continuation or modification of chemotherapy and/or clinical antitumor effects in patients with malignant gliomas.