title: 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.
authors.affiliation: Department of Neurosurgery, National Hospital Organization Kyoto Medical Center.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Aoki
authors.forename: Ryo
authors.initials: R
authors.lastname: Nishikawa
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Sugiyama
authors.forename: Naosuke
authors.initials: N
authors.lastname: Nonoguchi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kawabata
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Mishima
authors.forename: Jun-Ichi
authors.initials: JI
authors.lastname: Adachi
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kurisu
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Yamasaki
authors.forename: Teiji
authors.initials: T
authors.lastname: Tominaga
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kumabe
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ueki
authors.forename: Fumi
authors.initials: F
authors.lastname: Higuchi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishikawa
authors.forename: Hideo
authors.initials: H
authors.lastname: Takeshima
authors.forename: Shinji
authors.initials: S
authors.lastname: Yamashita
authors.forename: Kazunori
authors.initials: K
authors.lastname: Arita
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hirano
authors.forename: Shinobu
authors.initials: S
authors.lastname: Yamada
authors.forename: Masao
authors.initials: M
authors.lastname: Matsutani