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Preclinical Experimental Therapeutics |
The Johns Hopkins Oncology Center, 401 North Broadway, Baltimore, MD 21231
1 Address correspondence and reprint requests to Stuart A. Grossman, The Johns Hopkins Oncology Center, Bunting-Blaustein Cancer Research Bldg., Rm. G93, 1650 Orleans St., Baltimore, MD 21231-1000.
Although dexamethasone is very effective for controlling peritumoral cerebral edema, it is associated with distressing side effects that decrease the quality of life for many patients. One potential mechanism to explain the ability of dexamethasone to repair blood-brain barrier dysfunction is through the inhibition of cyclooxygenase-2 (COX-2). The purpose of this study was to determine in a rat brain tumor model whether SC-236, a selective COX-2 inhibitor, is as effective as dexamethasone. Twenty-nine adult male Fischer 344 rats were implanted with intracerebral 9L gliosarcomas and divided into 3 treatment groups. One group (n = 9) served as controls, another (n = 9) was treated with dexamethasone (3 mg/kg p.o. daily), and a third group (n = 11) received SC-236 (3 mg/kg p.o. daily). A survival study was performed. The median survival in the control group was 16 days, compared with 23 days for the dexamethasone group and 23 days for the COX-2 inhibitor group. Kaplan-Meier analysis on pairwise group comparisons showed improved survival that was statistically significant for each treatment group compared with the control group (log-rank test P = 0.009 for dexamethasone to control and P = 0.005 for COX-2 to control), and no significant difference in survival for the COX-2 compared with dexamethasone (log-rank test P = 0.2). These results suggest that a selective COX-2 inhibitor appears to be as effective as dexamethasone in prolonging survival in a rat brain tumor model.
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