Local delivery of doxorubicin for the treatment of malignant brain tumors in rats.
BACKGROUND
Local delivery of carmustine (BCNU) via biodegradable polymers has been shown to improve survival in patients with glioblastoma multiforme (GBM). In the current study, we hypothesized that local delivery of an anthracycline antibiotic, doxorubicin (DOX), might act to improve the survival of animals bearing experimental intracranial glioma.


METHODS
Polyanhydride polymers (PCPP-SA), containing either 3% or 5% ADR by weight, were prepared using the mix-melt method. Forty male Fisher 344 rats received an intracranial challenge with a lethal dose of 9L gliosarcoma cells. Five days later, they received DOX or blank polymer. There were a total of four treatment groups: (1) blank polymer; (2) 3% DOX polymer; (3) 5% DOX polymer, and (4) control group with no polymer.


RESULTS
Compared to control animals treated with no polymers or blank polymer, animals receiving DOX had significantly extended survival. The median survival for the control group was 21 days vs. 34 days (p < 0.01) for the 3% DOX group and 45 days (p < 0.0001) for the 5% DOX group.


CONCLUSIONS
Doxorubicin, when delivered locally, is an effective monotherapeutic agent against experimental intracranial glioma.
Lesniak
Maciej S
MS
Division of Neurosurgery, The University of Chicago Pritzker School of Medicine, 5841 S. Maryland Ave-MC3026, Chicago, Illinois 60637, USA. mlesniak@surgery.bsd.uchicago.edu
Upadhyay
Urvashi
U
Goodwin
Rory
R
Tyler
Betty
B
Brem
Henry
H
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000633:toxicity; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000633:toxicity; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D003652:Decanoic Acids / Q000008:administration & dosage* / Q000633:toxicity; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000008:administration & dosage* / Q000633:toxicity; D004337:Drug Carriers / Q000008:administration & dosage / Q000633:toxicity; D004343:Drug Implants; D005260:Female; D018316:Gliosarcoma / Q000188:drug therapy* / Q000473:pathology; D011091:Polyesters / Q000008:administration & dosage* / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344
D000903:Antibiotics, Antineoplastic; D001672:Biocompatible Materials; D003652:Decanoic Acids; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004343:Drug Implants; D011091:Polyesters; D004317:Doxorubicin; C055401:decanedioic acid-4,4'-(1,3-propanediylbis(oxy))bis(benzoic acid) copolymer