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-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 micrograms/day or RC-160 microcapsules releasing 38 micrograms/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 micrograms/day given alone or in combination with RC-160 microcapsules releasing 76 micrograms/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.
Yano
T
T
Endocrine Institute, Veterans Affairs Medical Center, New Orleans, Louisiana 70146.
Pinski
J
J
Szepeshazi
K
K
Milovanovic
S R
SR
Groot
K
K
Schally
A V
AV
D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002214:Capsules; D002455:Cell Division / Q000187:drug effects; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004702:Endocrine Glands / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors*; D013006:Growth Hormone / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008969:Molecular Sequence Data; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000033:anatomy & histology; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012669:Seminal Vesicles / Q000033:anatomy & histology; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013737:Testis / Q000033:anatomy & histology; D013739:Testosterone / Q000097:blood
D000970:Antineoplastic Agents; D002214:Capsules; D003692:Delayed-Action Preparations; C051458:vapreotide; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D013004:Somatostatin; D007986:Luteinizing Hormone; D013006:Growth Hormone; C062876:cetrorelix