BROPIRIMINE AS NEOADJUVANT THERAPY DECREASES RESIDUAL DISEASE AND EXPRESSION OF MARKERS PCNA AND TGF-BETA(1) IN A RAT ORTHOTOPIC PROSTATE ADENOCARCINOMA

The role of bropirimine in prostate cancer remains unexplored. To addr ess the efficacy of this immune modulator as neoadjuvant therapy we ut ilized the orthotopic placement of the Dunning AT-3 tumor. 2.4-2.6 x 1 0(6) Dunning AT-3 cells were injected into the ventral prostates of 50 Copenhagen X Fischer rats. Animals were then divided into 5 groups co nsisting of: 1) untreated controls; 2) those treated with ventral pros tatectomy alone (performed 10-12 days following tumor cell inoculation ); 3) those treated with ventral prostatectomy plus bropirimine (10 mg /kg) on postimplantation days 1, 3, 5, 10 and II; 4) those treated,vit h ventral prostatectomy plus bropirimine (100 mg/kg), at the same sche dule; and 5) those treated with ventral prostatectomy plus bropirimine (500 mg/kg), at the same schedule. Animals were sacrificed 10 days af ter prostatectomy, autopsied, and residual disease was weighed Prostat e weights upon removal following neoadjuvant treatment and residual di sease remaining after 20-22 days were expressed in grams (g). Followin g prostatectomy, mean prostate weights were: Group 2, 0.67 +/- 0.11; G roup 3, 0.53 +/- 0.11; Group 4, 0.54 +/- 0.12; Group 5, 0.44 +/- 0.09. The effect of bropirimine was significant (p = 0.0001) by multiple re gression analysis. in addition, mean residual tumor weights (expressed in grams) after 20-22 days were: Group 1, 12.7 +/- 1.9; Group 2, 6.7 +/- 4.8; Group 3, 5.2 +/- 5.9; Group 4, 3.8 +/- 3.5; and Group 5, 2.8 +/- 3.5. The effect of bropirimine was nor significant (p = 0.07) by m ultiple regression analysis. However; prostatectomy alone, by Student' s t test, significantly (p = 0.04) reduced residual mean tumor weights by 47% and the additional effect of bropirimine upon residual disease was significant (p = 0.038) if a Chi-square analysis is applied Final ly, a multivariate analysis of the overall effect of bropirimine in ra ts treated with prostatectomy, was significant (p = 0.002). The effect of bropirimine on expression of proliferating cell nuclear antigen (P CNA) and transforming growth factor beta(1) (TGF-beta(1)) was also eva luated immunohistochemically and expression of both tumor markers was significantly reduced (p<0.05). We conclude that bropirimine may have a role as a neoadjuvant therapy when combined with prostatectomy.