THERAPEUTIC EFFECTS OF LOCAL-DELIVERY OF DEXAMETHASONE ON EXPERIMENTAL BRAIN-TUMORS AND PERITUMORAL BRAIN EDEMA

To determine if dexamethasone administered by osmotic pump directly to brain tumors would control peritumoral edema and at the same time sup press tumor growth and prolong survival, the authors studied experimen tal brain tumors produced in 102 rabbits by implanting VX2 carcinoma c ells. Of these, 58 animals were separated into three treatment groups: Group 1 included 15 untreated rabbits; Group 2 included 18 rabbits tr eated with systemic dexamethasone (4 mg/kg/day); and Group 3 included 25 rabbits treated with local dexamethasone (0.24 mg/day) delivered by osmotic pump. Systemic or local dexamethasone was administered from D ay 3 or Day 7 after tumor implantation, and animals were sacrificed on Day 13. A survival study was performed with 44 rabbits separated into the same treatment groups, beginning drug delivery on Day 7. Brain wa ter content in the white matter of sacrificed animals was measured by the specific gravity method. The length and width of the brain tumors in all animals were measured and the tumor volume estimated. Findings showed that systemic and local dexamethasone administered from Day 3 o r Day 7 was associated with a significant (5% level) inhibition of tum or volume as well as a mean reduction of brain edema in most tested si tes. Systemic and local dexamethasone therapy also resulted in a signi ficant (5% level) increase in survival time relative to the untreated group. These short-term results suggest that locally delivered dexamet hasone may constitute a clinically important therapeutic modality.