REGRESSION OF RAT MAMMARY-TUMORS BY A POTENT LUTEINIZING-HORMONE-RELEASING HORMONE ANALOG (LEUPROLIDE) ADMINISTERED VAGINALLY

  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (4) , 1869-1874
Abstract
Potent LHRH analogues are known to cause regression of hormone-dependent mammary tumors. High and long-lasting serum levels of a potent LHRH analogue [desglycyl10-(D-leucyl6) LHRH ethylamide, leuprolide] resulted from vaginal administration which effectively caused down regulation in the pituitary by chronic treatment. Regression of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in Sprague-Dawley rats by consecutive daily vaginal administration of leuprolide was investigated. In untreated rats, 71% of tumors were growing at 8 wk, whereas after i.p. injection of leuprolide (500 .mu.g/kg) all tumors were regressing 2 wk after commencement of treatment and 86.7% of tumors disappeared by 8 wk. Vaginal administration of 100 .mu.g/kg for 8 wk produced regression in 80% of tumors and disappearance in 35%. The vaginal administration of a higher dose (500-5000 .mu.g/kg) produced highly significant antitumor effects [regression in 82.2 .+-. 4.0% (SE) and disappearance in 52.9 .+-. 2.1%]. These results are consistent with the effects produced by ovariectomy. Whereas 13 and 7 new tumors appeared in untreated rats and those treated vaginally with leuprolide (100 .mu.g/kg), respectively, only 1 or 2 tumors appeared in i.p. an vaginally (above 500 .mu.g/kg) treated rats during treatment. Histological classification of the mammary tumors after treatment indicated therapeutic effects simialr to those shown by tumor size determination. Vaginal application of leuprolide at doses above 500 .mu.g/kg might be a potentially useful mtehod for antitumor therapy.