INTRALESIONALLY IMPLANTED CISPLATIN CURES PRIMARY BRAIN-TUMOR IN RATS

Background and Objectives: Chemotherapy has added little to the overal l survival of the patients with primary malignant brain tumors, primar ily 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 cel ls and drug-free or cisplatin-loaded polymer were administered through a right frontal lobe cannula in male Fischer 344 rats. Tumor cells we re infused on day 0 and polymer on day 7. Animals were monitored for 6 0 days. Results: In experiment one, 0.5 mg/m(2) 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 2 4 +/- 4 days (p = 2.5 x 10(-9)). Evidence of clinical or histologic br ain toxicity was minimal. In a second experiment, using drug-free poly mer (n = 7), MST was 24 +/- 3 days. This was compared against an MST o f 24 +/- 4 days in the tumor control group (n = 7) and 49 +/- 7 days i n a cisplatin-polymer treated group (n = 6). In a third experiment, tw o doses of drug-free polymer and three doses of cisplatin-loaded polym er were tested in normal nontumor-bearing rats and found to be well to lerated. Conclusions: Intralesional sustained release of cisplatin fro m biodegradable polymer is safe and effective for the treatment of bra in 9L gliosarcoma in rats. (C) 1997 Wiley-Liss, Inc.