A multicenter phase I/II study of the BCNU implant (Gliadel(®) Wafer) for Japanese patients with malignant gliomas.

Carmustine (BCNU) implants (Gliadel(®) Wafer, Eisai Inc., New Jersey, USA) for the treatment of malignant gliomas (MGs) were shown to enhance overall survival in comparison to placebo in controlled clinical trials in the United States and Europe. A prospective, multicenter phase I/II study involving Japanese patients with MGs was performed to evaluate the efficacy, safety, and pharmacokinetics of BCNU implants. The study enrolled 16 patients with newly diagnosed MGs and 8 patients with recurrent MGs. After the insertion of BCNU implants (8 sheets maximum, 61.6 mg BCNU) into the removal cavity, various chemotherapies (including temozolomide) and radiotherapies were applied. After placement, overall and progression-free survival rates and whole blood BCNU levels were evaluated. In patients with newly diagnosed MGs, the overall survival rates at 12 months and 24 months were 100.0% and 68.8%, and the progression-free survival rate at 12 months was 62.5%. In patients with recurrent MGs, the progression-free survival rate at 6 months was 37.5%. There were no grade 4 or higher adverse events noted due to BCNU implants, and grade 3 events were observed in 5 of 24 patients (20.8%). Whole blood BCNU levels reached a peak of 19.4 ng/mL approximately 3 hours after insertion, which was lower than 1/600 of the peak BCNU level recorded after intravenous injections. These levels decreased to less than the detection limit (2.00 ng/mL) after 24 hours. The results of this study involving Japanese patients are comparable to those of previous studies in the United States and Europe.

Management of glioblastoma.

Glioblastoma multiforme (GBM) are among the most devastating neoplasms claiming the lives of patients within a median of 1 year after diagnosis. Treatment of GBM requires a multidisciplinary approach. Treatments include surgery, radiotherapy, chemotherapy and so on. Temozolomide (TMZ) has emerged as an active agent against malignant gliomas. On the basis of the work by the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada, concurrent radiotherapy and the oral alkylating agent TMZ followed by adjuvant TMZ has become the standard of care for patients with newly diagnosed GBM, although the methylation status of the O(6)-mehylguanine-DNA methyltransferase promoter is predictive for survival of GBM patients. Gliadel is a biodegradable polymer wafer impregnated with carmustine. Gliadel has been one of the few treatment modalities to demonstrate a statistical benefit in patients with malignant glioma. These new FDA approved drugs advanced the treatment of malignant glioma, but more progress is needed. Patients require improvements in chemotherapy, surgery, radiotherapy, molecular targeted therapy, immunotoxin using the convection-enhanced delivery and more.