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: Tomokazu Aoki, Ryo Nishikawa, Kazuhiko Sugiyama, Naosuke Nonoguchi, Noriyuki Kawabata, Kazuhiko Mishima, Jun-ichi Adachi, Kaoru Kurisu, Fumiyuki Yamasaki, Teiji Tominaga, Toshihiro Kumabe, Keisuke Ueki, Fumi Higuchi, Tetsuya Yamamoto, Eiichi Ishikawa, Hideo Takeshima, Shinji Yamashita, Kazunori Arita, Hirofumi Hirano, Shinobu Yamada, Masao Matsutani, NPC-08 study group
• Journal: Neurologia medico-chirurgica (Neurol Med Chir (Tokyo)) Vol. 54 Issue 4 Pg. 290-301 ( 2014) ISSN: 1349-8029 [Electronic] Japan
• PMID: 24739422 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Alkylating
• Decanoic Acids
• Drug Implants
• Polyesters
• carmustine, poliferprosan 20 drug combination
• Carmustine

Topics

• Adult
• Aged
• Antineoplastic Agents, Alkylating (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Brain Neoplasms (drug therapy, radiotherapy, surgery)
• Carmustine (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Combined Modality Therapy
• Decanoic Acids (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Disease-Free Survival
• Drug Implants
• Female
• Gastrointestinal Diseases (etiology)
• Glioma (drug therapy, radiotherapy, surgery)
• Humans
• Japan
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy)
• Neoplasms, Second Primary (etiology)
• Nervous System Diseases (etiology)
• Polyesters (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Prospective Studies