Local delivery of interleukin-2 and adriamycin is synergistic in the treatment of experimental malignant glioma.
BACKGROUND
Local delivery of adriamycin (ADR) via biodegradable polymers has been shown to improve survival in rats challenged intracranially with 9L gliosarcoma. Likewise, local delivery of interleukin-2 (IL-2) has been shown to extend survival in experimental brain tumor models. In the current study, we hypothesized that local delivery of ADR and IL-2 might act synergistically against experimental intracranial glioma.


METHODS
Polyanhydride polymers (PCPP-SA) containing 5% ADR by weight were prepared using the mix-melt method. IL-2 polymer microspheres (IL-2 MS) were produced via the complex coacervation of gelatin and chondroitin sulfate in the presence of IL-2. Sixty male Fisher 344 rats received an intracranial challenge with a lethal dose of 9L gliosarcoma cells. In addition, a group of rats were injected with either IL-2 MS or empty microspheres. Five days later they received ADR or blank polymer. There were a total of four treatment groups: (1) empty microspheres, blank polymer; (2) empty microspheres, ADR polymer; (3) IL-2 MS, blank polymer; and (4) IL-2 MS, ADR polymer.


RESULTS
Compared to control animals treated with empty microspheres and blank polymer, animals receiving empty microspheres and ADR polymer (P < 0.0004), IL-2 MS and blank polymer (P < 0.0005), and IL-2 MS combined with ADR polymer (P < 0.0000002) all showed statistically significant improvement in survival. In addition, animals receiving the IL-2/ADR combination had significantly extended survival compared to either ADR or IL-2 alone (P < 0.000003 and P < 0.0004, respectively).


CONCLUSIONS
Both ADR and IL-2, when delivered locally, are effective monotherapeutic agents against experimental intracranial gliosarcoma. The combination ADR and IL-2 therapy is more effective than either agent alone.
Hsu
Wesley
W
Departments of Neurosurgery and Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Lesniak
Maciej S
MS
Tyler
Betty
B
Brem
Henry
H
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage; D016503:Drug Delivery Systems; D004357:Drug Synergism; D005260:Female; D018316:Gliosarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015552:Injections, Intralesional; D007276:Injections, Intraventricular; D007376:Interleukin-2 / Q000008:administration & dosage; D008863:Microspheres; D011108:Polymers; D051381:Rats; D011916:Rats, Inbred F344; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D011108:Polymers; D004317:Doxorubicin