A Multicenter Phase I/II Study of the BCNU Implant (Gliadel^® Wafer) for Japanese Patients with Malignant Gliomas

Abstract

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.

Rapid regression of glioblastoma following carmustine wafer implantation: A case report

“…A carmustine (bis-chloroethylnitrosourea, BCNU; an alkylating agent of the nitrosourea family) wafer (Gliadel ® ; Eisai Inc., Tokyo, Japan) is a controlled-release preparation of BCNU that is implanted into the brain (2). Carmustine wafers, lined along the wall of the resection cavity following tumor removal, exert antitumor effects on the residual tumor as adjuvant local chemotherapy.…”

“…This implant has been shown to enhance the overall survival of patients with malignant gliomas in controlled clinical trials in the United States and Europe (3). A prospective, multicenter phase-I/II study on Japanese patients was recently performed and the application of carmustine wafers has been covered by Japanese public health insurance since 2012 (2).…”

Cerebral Infarction Related to Carmustine Wafers in Glioblastoma: A Case Report

“…1) However, many adverse events (AEs) have been associated with the implantation of Gliadel, including cerebral edema, healing abnormalities, cerebrospinal fluid (CSF) leakage, intracranial infections, seizures, hydrocephalus, and cyst formation. 2–7) To the best of our knowledge, ischemia due to vasospasm is not a known complication of Gliadel. Here we present a case of primary glioblastoma (GBM) that showed an acute cerebral infarction certainly caused by vasospasm due to Gliadel.…”

Phase I/II Study of Temozolomide Plus Nimustine Chemotherapy for Recurrent Malignant Gliomas: Kyoto Neuro-oncology Group

“…2,3) The clinical benefit of adding bevacizumab to the treatment is controversial. 4–6,8) Gliadel wafers also have been often used, if possible. 8,9) Despite the advent of multimodal treatments, this tumor always recurs within 1 or 2 years.…”

“…4–6,8) Gliadel wafers also have been often used, if possible. 8,9) Despite the advent of multimodal treatments, this tumor always recurs within 1 or 2 years. Then, we don’t have any established second-line treatments.…”