Safety evaluation of high-dose BCNU-loaded biodegradable implants in Chinese patients with recurrent malignant gliomas

Abstract

ObjectivesMalignant gliomas are common primary brain tumors with dismal prognosis. The blood–brain barrier and unacceptable systemic toxicity limit the employment of chemotherapeutic agents. BCNU-impregnated biodegradable polymers (Gliadel®) have been demonstrated to prolong the survival of patients with malignant gliomas. Until now, no biodegradable drug delivery system has been commercially available in China. In the present study, we evaluated the safety of implants with high-dose BCNU in Chinese patients with recurrent malignant gliomas. Patients and methodsAdults with supratentorial recurrent malignant glioma were eligible. High-dose BCNU-loaded PLGA implants (20mg of BCNU in each implant) were placed in the debulking cavity. The implants were investigated by a classical 3+3 design. Four levels of BCNU, up to 12 implants, were evaluated. Pharmacokinetic sampling was performed. The toxicity of the implants and the survival of patients were recorded. ResultsFifteen recurrent patients were enrolled with 12 glioblastomas and 3 anaplastic gliomas. Among 15 patients, 3 were treated with 3 implants (60mg of BCNU), 3 with 6 implants (120mg), 3 with 9 implants (180mg) and 6 with 12 implants (240mg). No dose-limiting toxicity was observed in the cohort of patients. Subgaleal effusion was the most common adverse event, presenting in 7 patients (46.7%). The median overall survival (OS) was 322days (95% CI, 173–471days). The 6-month, 1-year and 2-year survival rates were 66.7%, 40% and 13.3%, respectively. ConclusionsThe high-dose BCNU-loaded PLGA implants were safe for Chinese patients with recurrent malignant gliomas and further investigation for efficacy is warranted.