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

Abstract

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‐Cys‐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 μg/day or RC‐160 microcapsules releasing 38 μg/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 μg/day given alone or in combination with RC‐160 microcapsules releasing 76 μg/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.