EFFECT OF MICROCAPSULES OF LUTEINIZING-HORMONE-RELEASING HORMONE ANTAGONIST SB-75 AND SOMATOSTATIN ANALOG RC-160 ON ENDOCRINE STATUS AND TUMOR-GROWTH IN THE DUNNING R-3327H RAT PROSTATE-CANCER MODEL

Inhibitory effects of sustained delivery systems (microcapsules) of the modern antagonist of luteinizing hormone-releasing hormone [Ac-D-Nal(2)1, D-Phe(4Cl)2. D-Pal(3) 3, D-Cit6 D-Ala10]LH-RH (SB-75) or the potent somatostatin analog D-Phe-Cvs-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) were investigated in the Dunning R-3327H rat prostate cancer model. In the first experiment. the treatment was started 4 months after tumor transplantation, when the tumors measured approximately 2 cm3. Tumor volumes and weights were significantly reduced by SB-75 microcapsules releasing 48-mu-g/day or RC-160 microcapsules releasing 38-mu-g/day given alone, as compared with the control. The combination of these two analogs showed a synergistic effect. In the second experiment. the treatment was started 7 months after tumor transplantation, when the tumors were well developed and measured about 16 cm3. In addition to a significant reduction in volume, weight, and growth rate of tumors. histological signs of tumor regression were found in the groups treated with SB-75 microcapsules releasing 72-mu-g/day given alone or in combination with RC-160 microcapsules releasing 76-mu-g/day, but not with RC-160 alone. No synergistic effect of the combination therapy was found in the second experiment. Serum testosterone levels decreased to undetectable levels and LH levels were also diminished within 2 weeks by administration of SB-75 alone or in combination with RC-160. In both experiments, the weights of testes, ventral prostate, and seminal vesicles were greatly reduced by administration of SB-75 alone or in combination with RC-160. Our results suggest that the combined therapy with microcapsules of SB-75 and RC-160, started soon after the diagnosis of prostate cancer is made, could improve therapeutic response.