Experimental study of intraoperative local chemotherapy with fibrin glue containing nitrosourea for malignant gliomas.
BACKGROUND
Local control of the tumor bed after removal of a tumor is one of the most important points in the treatment of malignant gliomas. This study was designed to examine whether fibrin glue is useful as a vehicle for sustained release of intraoperative local chemotherapy with nitrosourea (ACNU).


METHODS
The growth-inhibiting activity of ACNU on C6 glioma cells and ACNU released into 5-mL supernatant saline from fibrin glue containing 5 mg/mL (10 mg) of ACNU was measured in vitro. C6 tumor inoculated in rat brains was covered with fibrin glue containing either 2 mg/mL or 5 mg/mL of ACNU for 5 days, and the histologic changes were examined.


RESULTS
ACNU inhibited the growth of C6 glioma cells in a dose-dependent manner, and the drug concentration required for 50% inhibition of cell growth (IC50) was about 4 micrograms/mL with 1 hour of treatment. Although about 50% of all ACNU included in the fibrin glue was released in the first hour, an effective concentration over the value of IC50 was sustained even after 12 hours. A histologic examination showed tumor cells damaged within a depth of about 2-3 mm from the tumor surface covered with fibrin glue containing ACNU.


CONCLUSIONS
Fibrin glue may be useful as a vehicle for sustained-release chemotherapy, and intraoperative local chemotherapy with fibrin glue containing anticancer agents such as nitrosourea may be helpful in the local control of malignant gliomas.
Kabuto
M
M
Department of Neurosurgery, Fukui Medical School, Japan.
Kubota
T
T
Kobayashi
H
H
Nakagawa
T
T
Arai
Y
Y
Kitai
R
R
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004358:Drug Therapy / Q000379:methods*; D015718:Fibrin Tissue Adhesive / Q000494:pharmacology*; D005910:Glioma / Q000188:drug therapy*; D008297:Male; D015376:Nimustine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D016896:Treatment Outcome
D015718:Fibrin Tissue Adhesive; D015376:Nimustine