REGRESSION OF RAT MAMMARY-TUMORS EFFECTED BY A GONADOLIBERIN ANALOG

Abstract

A synthetic analog of gonadoliberin (gonadtropin releasing factor or luteinizing hormone/follicle stimulating hormone releasing hormone), designated A-43818, was evaluated for its ability to effect regression of carcinogen induced mammary tumors in the Sprague-Dawley rat. This analog, specifically (D-leucyl6, desglycyl-NH210, prolyl ethylamide9)gonadoliberin, is a potent synthetic luteinizing hormone/follicle stimulating hormone-releasing hormone at low dose levels but, at the higher dose levels used in these studies, the effect appears to be that of a potent gonadoliberin antagonist. Administration of 5 or 20 .mu.g of A-43818 per day to tumor bearing rats was as effective as ovariectomy in causing mammary tumor regression. At least 80% of the tumors in the A-43818 treated animals underwent regression. About 1/2 of the regressing tumors disappeared in the 6 wk period of continuous treatment, and, unlike the 0.9% NaCl solution control group, no new tumors appeared during the treatment period. A subsequent 4 wk period of drug withdrawal resulted in the regrowth of palpable tumors and the appearance of new tumors, most of which again regressed on further A-43818 administration.