Intralesionally implanted cisplatin cures primary brain tumor in rats.
OBJECTIVE
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.
Kong
Q
Q
Department of Surgery, University of Colorado Health Sciences Center, Denver 80262, USA.
Kleinschmidt-Demasters
B K
BK
Lillehei
K O
KO
D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage*; D003692:Delayed-Action Preparations; D004343:Drug Implants; D018316:Gliosarcoma / Q000188:drug therapy* / Q000473:pathology; D019344:Lactic Acid / Q000008:administration & dosage; D008297:Male; D009368:Neoplasm Transplantation; D011091:Polyesters; D011108:Polymers / Q000008:administration & dosage; D051381:Rats; D011916:Rats, Inbred F344; D016019:Survival Analysis
D003692:Delayed-Action Preparations; D004343:Drug Implants; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D002945:Cisplatin