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

OBJECTIVES: Malignant 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 METHODS: Adults 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. RESULTS: Fifteen recurrent patients were enrolled with 12 glioblastomas and 3 anaplastic gliomas. Among 15 patients, 3 were treated with 3 implants (60 mg of BCNU), 3 with 6 implants (120 mg), 3 with 9 implants (180 mg) and 6 with 12 implants (240 mg). 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 322 days (95% CI, 173-471 days). The 6-month, 1-year and 2-year survival rates were 66.7%, 40% and 13.3%, respectively. CONCLUSIONS: The high-dose BCNU-loaded PLGA implants were safe for Chinese patients with recurrent malignant gliomas and further investigation for efficacy is warranted.

Experimental study on the osseointegration of foam TiC/Ti composites.

Macroporous ceramics have demonstrated osteoconductive properties because of their biocompatibility and 3D macroporous structure, and these materials have recently been widely studied as bone replacement materials. The foam TiC/Ti composites discussed in this study have good mechanical properties, balancing out metallic toughness and ceramic strength. Furthermore, because of the high porosity and pore connectivity of these TiC/Ti composites, they have the potential to be a new bone replacement material. The purpose of this study was to evaluate the osseointegration of foam TiC/Ti composites, preliminarily discuss the TiC/Ti ossification mechanism, and to obtain reliable data on the use of foam TiC/Ti composites as bone replacement materials. The foam TiC/Ti composites were sited in 40 Japanese white rabbits for 4, 8, 12 and 24 weeks. The foam TiC/Ti composites were compared to foam SiC. M-CT (micro-computed tomography) analysis, histological analysis, SEM (scanning electron microscopy) observation and EDS (energy-dispersive x-ray spectrometer) analysis were conducted to estimate the osseointegration of the materials. The histological observations and quantitative analysis exhibited significantly more ossification area (volume), trabeculae maturity, and calcium and phosphorus content in the foam TiC/Ti composites compared to the foam SiC (p < 0.05). The results from this study suggest that the foam TiC/Ti composites possess good osseointegration capacity and have the potential to be a new bone replacement material.