Intralesionally implanted cisplatin cures primary brain tumor in rats.

Abstract

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.

• Authors: Q Kong, B K Kleinschmidt-Demasters, K O Lillehei
• Journal: Journal of surgical oncology (J Surg Oncol) Vol. 64 Issue 4 Pg. 268-73 (Apr 1997) ISSN: 0022-4790 [Print] United States
• PMID: 9142181 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Delayed-Action Preparations
• Drug Implants
• Polyesters
• Polymers
• Lactic Acid
• poly(lactide)
• Cisplatin

Topics

• Animals
• Brain Neoplasms (drug therapy, pathology)
• Cisplatin (administration & dosage)
• Delayed-Action Preparations
• Drug Implants
• Gliosarcoma (drug therapy, pathology)
• Lactic Acid (administration & dosage)
• Male
• Neoplasm Transplantation
• Polyesters
• Polymers (administration & dosage)
• Rats
• Rats, Inbred F344
• Survival Analysis