1. A multicenter phase I/II study of the BCNU implant (Gliadel(®) Wafer) for Japanese patients with malignant gliomas.
- Author
-
Aoki T, Nishikawa R, Sugiyama K, Nonoguchi N, Kawabata N, Mishima K, Adachi J, Kurisu K, Yamasaki F, Tominaga T, Kumabe T, Ueki K, Higuchi F, Yamamoto T, Ishikawa E, Takeshima H, Yamashita S, Arita K, Hirano H, Yamada S, and Matsutani M
- Subjects
- Adult, Aged, Antineoplastic Agents, Alkylating adverse effects, Antineoplastic Agents, Alkylating pharmacokinetics, Antineoplastic Agents, Alkylating therapeutic use, Brain Neoplasms radiotherapy, Brain Neoplasms surgery, Carmustine adverse effects, Carmustine pharmacokinetics, Carmustine therapeutic use, Combined Modality Therapy, Decanoic Acids adverse effects, Decanoic Acids pharmacokinetics, Decanoic Acids therapeutic use, Disease-Free Survival, Drug Implants, Female, Gastrointestinal Diseases etiology, Glioma radiotherapy, Glioma surgery, Humans, Japan, Kaplan-Meier Estimate, Male, Middle Aged, Neoplasm Recurrence, Local drug therapy, Neoplasms, Second Primary etiology, Nervous System Diseases etiology, Polyesters adverse effects, Polyesters pharmacokinetics, Polyesters therapeutic use, Prospective Studies, Antineoplastic Agents, Alkylating administration & dosage, Brain Neoplasms drug therapy, Carmustine administration & dosage, Decanoic Acids administration & dosage, Glioma drug therapy, Polyesters administration & dosage
- 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.
- Published
- 2014