Intralesionally implanted cisplatin cures primary brain tumor in rats.

BACKGROUND AND OBJECTIVES

Chemotherapy has added little to the overall survival of the patients with primary malignant brain tumors, primarily due to its difficulty penetrating the blood-brain barrier. Use of polymers, releasing high doses of chemotherapy locally over time, is a promising new treatment strategy. Three experiments were conducted to test the effect of cisplatin, released from biodegradable polymer, on rats with 1 week established brain tumor.

METHODS

9L gliosarcoma cells and drug-free or cisplatin-loaded polymer were administered through a right frontal lobe cannula in male Fischer 344 rats. Tumor cells were infused on day 0 and polymer on day 7. Animals were monitored for 60 days.

RESULTS

In experiment one, 0.5 mg/m2 of cisplatin loaded in polymer resulted in a mean survival time (MST) of 51 +/- 14 days with 63% (10/16) rats surviving to day 60. MST for the control group was 24 +/- 4 days (p = 2.5 x 10(-9)). Evidence of clinical or histologic brain toxicity was minimal. In a second experiment, using drug-free polymer (n = 7), MST was 24 +/- 3 days. This was compared against an MST of 24 +/- 4 days in the tumor control group (n = 7) and 49 +/- 7 days in a cisplatin-polymer treated group (n = 6). In a third experiment, two doses of drug-free polymer and three doses of cisplatin-loaded polymer were tested in normal nontumor-bearing rats and found to be well tolerated.

CONCLUSIONS

Intralesional sustained release of cisplatin from biodegradable polymer is safe and effective for the treatment of brain 9L gliosarcoma in rats.