Histologic changes in the rat prostate cancer model after treatment with somatostatin analogs and D-Trp-6-LH-RH.

Histopathologic changes produced during the treatment of Dunning R3327 prostate cancer with new superactive somatostatin analogs (RC-121 and RC-160) and D-Trp-6 analog of luteinizing hormone-releasing hormone agonist (D-Trp-6-LH-RH) were studied. A significant reduction of the tumor weight could be observed in all treated groups, but the greatest decrease in the tumor volume was seen in the groups receiving the combination of the somatostatin analog and D-Trp-6-LH-RH. Histologically, the treatments resulted in a loss of the tumorous glandular elements and the proliferation of the stromal cells. In the tumors treated with somatostatin analogs, the amount of connective tissue was greatly increased and was accompanied by the appearance of thick collagenous fibers. In the D-Trp-6-LH-RH treated groups, regressive changes in the epithelium were seen in addition to the proliferation of connective tissue. The greatest histologic improvement was observed in the group treated with the combination of RC-160 and D-Trp-6-LH-RH. This histopathologic evaluation clearly supports our contention that superactive analogs of somatostatin greatly potentiate the inhibitory effect of D-Trp-6-LH-RH on the growth of Dunning prostate tumors and may improve the clinical response in patients with prostate cancer.