Treatment of recurrent malignant glioma with BCNU-fluosol and oxygen inhalation. A phase I-II study

Objectives: To evaluate the toxicity and response rate following BCNU with oxygen inhalation and escalatingdosages of fluosol administered to patients with radiographic progression of malignant glioma after definitivesurgery and radiotherapy. Method: This single arm, phase I-II multicenter trial, enrolled 99 patients withmalignant gliomas recurrent after definitive surgery and radiotherapy. All patients received a fixed dose(200 mg/m²) of BCNU along with 100% oxygen and fluosol, a perfluorochemical. Fluosol doses were escalat-edbetween patients (150, 275, 400 and 600 ml/m²). Treatment was repeated every 6 weeks for a maximum of 6cycles. Patients were assessed for toxicity at the time of infusion and sequentially thereafter. Response wasevaluated clinically and radiologically at least every 6 weeks. Results: Treatment was well tolerated. Dosereductions were required at least once in 18 patients, treatment delays were necessary at least once in 33patients. Grade 3-4 leukopenia occurred in 6 patients (12 events), grade 3-4 thrombocytopenia in 10 patients(25 events) and grade 3-4 liver enzymes elevations in 18 patients (31 events). Higher fluosol dosages did notproduce increases in toxicity or responses. Response or stabilization was seen in 57% (38% were stabiliza-tions)of the patients who entered the trial with progressive disease. The median time to progression was 45weeks, and median survival was 66 weeks for patients who had response or stabilization. For patients withglioblastoma response/stabilization was seen in 45% with a mean duration of 24 weeks, for patients withanaplastic astrocytoma response/stabilization was seen in 68% with a mean duration of 50 weeks. Conclusion:This treatment regimen is well tolerated. Our results suggest fluosol may enhance the effectiveness of BCNUfor the treatment of recurrent malignant gliomas. Future studies will be performed using fluosol at the dose of400 ml/m².