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 che motherapy is a promising new strategy in the treatment of high-grade g liomas. We examine the benefit of local delivery of cisplatin, via bio degradable polymer, in the treatment of intracranial glioma in rats. T his treatment is compared against intralesionally administered free ci splatin and systemic cisplatin. METHODS: The Fischer 344 9L gliosarcom a 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 i nitiated on Day 7. In Experiment 1, polymer alone was infused intrales ionally to rule out any inherent toxic or tumoricidal properties. In E xperiment 2, polymer impregnated with 0.5, 5.0, and 25 mg/m(2) cisplat in was infused intralesionally. In Experiment 3, the most effective do se of drug containing polymer was compared against a similar dose of i ntralesionally administered free cisplatin and the systemic administra tion of cisplatin. RESULTS: In Experiment 1, polymer alone demonstrate d no inherent toxic or tumoricidal properties. In Experiment 2, polyme r impregnated with 0.5 mg/m(2) was 100% effective in eradicating intra cranial tumor with minimal histological evidence of toxicity. At the 5 .0 and 25 mg/m(2) doses, local brain toxicity was significant. In Expe riment 3, at Day 60, 8 of 12 animals treated with polymer containing 0 .5 mg/m(2) cisplatin were alive and tumor free. This compared with 3 o f 13 tumor-free survivors for the group treated with intralesionally a dministered free cisplatin, and 0 of 13 and 0 of 11 survivors for the 50 and 100 mg/m(2) intraperitoneally administered doses, respectively. CONCLUSION: The local instillation of cisplatin-impregnated biodegrad able polymer, allowing the sustained release of high-dose chemotherapy locally, seems to be effective treatment for intracranial 9L gliosarc oma in the rat. Treatment was superior to intralesionally administered free or systemic cisplatin.