Efficacy of intralesionally administered cisplatin-impregnated biodegradable polymer for the treatment of 9L gliosarcoma in the rat.
OBJECTIVE
Use of biodegradable polymers for the local delivery of chemotherapy is a promising new strategy in the treatment of high-grade gliomas. We examine the benefit of local delivery of cisplatin, via biodegradable polymer, in the treatment of intracranial glioma in rats. This treatment is compared against intralesionally administered free cisplatin and systemic cisplatin.


METHODS
The Fischer 344 9L gliosarcoma rat model was used with a cannula placed in the right frontal lobe. On Day 0, 5 x 10(3) 9L gliosarcoma cells were infused. Treatment was initiated on Day 7. In Experiment 1, polymer alone was infused intralesionally to rule out any inherent toxic or tumoricidal properties. In Experiment 2, polymer impregnated with 0.5, 5.0, and 25 mg/m2 cisplatin was infused intralesionally. In Experiment 3, the most effective dose of drug containing polymer was compared against a similar dose of intralesionally administered free cisplatin and the systemic administration of cisplatin.


RESULTS
In Experiment 1, polymer alone demonstrated no inherent toxic or tumoricidal properties. In Experiment 2, polymer impregnated with 0.5 mg/m2 was 100% effective in eradicating intracranial tumor with minimal histological evidence of toxicity. At the 5.0 and 25 mg/m2 doses, local brain toxicity was significant. In Experiment 3, at Day 60, 8 of 12 animals treated with polymer containing 0.5 mg/m2 cisplatin were alive and tumor free. This compared with 3 of 13 tumor-free survivors for the group treated with intralesionally administered free cisplatin, and 0 of 13 and 0 of 11 survivors for the 50 and 100 mg/m2 intraperitoneally administered doses, respectively.


CONCLUSIONS
The local instillation of cisplatin-impregnated biodegradable polymer, allowing the sustained release of high-dose chemotherapy locally, seems to be effective treatment for intracranial 9L gliosarcoma in the rat. Treatment was superior to intralesionally administered free or systemic cisplatin.
Lillehei
K O
KO
Department of Surgery, Colorado State University School of Veterinary Medicine, Fort Collins, USA.
Kong
Q
Q
Withrow
S J
SJ
Kleinschmidt-DeMasters
B
B
D000818:Animals; D001673:Biodegradation, Environmental; D001932:Brain Neoplasms / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D018316:Gliosarcoma / Q000188:drug therapy*; D007274:Injections, Intraperitoneal; D008297:Male; D011108:Polymers; D051381:Rats; D011916:Rats, Inbred F344
D004343:Drug Implants; D011108:Polymers; D002945:Cisplatin