Regression of rat mammary tumors by a potent luteinizing hormone-releasing hormone analogue (leuprolide) administered vaginally.
Potent luteinizing hormone-releasing hormone analogues are known to cause regression of hormone-dependent mammary tumors. We have observed that high and long-lasting serum levels of a potent luteinizing hormone-releasing hormone analogue [desglycyl10-(D-leucyl6) luteinizing hormone-releasing hormone 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 weeks, whereas after i.p. injection of leuprolide (500 micrograms/kg) all tumors were regressing 2 weeks after commencement of treatment and 86.7% of tumors disappeared by 8 weeks. Vaginal administration of 100 micrograms/kg for 8 weeks produced regression in 80% of tumors and disappearance in 35%. The vaginal administration of a higher dose (500 to 5000 micrograms/kg) produced highly significant antitumor effects [regression in 82.2 +/- 4.0% (S.E.) 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 micrograms/kg), respectively, only one or two tumors appeared in i.p. and vaginally (above 500 micrograms/kg) treated rats during treatment. Histological classification of the mammary tumors after treatment indicated therapeutic effects similar to those shown by tumor size determination. Thus, it was concluded that vaginal application of leuprolide at doses above 500 micrograms/kg might be a potentially useful method for antitumor therapy.
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D007700:Kinetics; D016729:Leuprolide; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D014621:Vagina
D000970:Antineoplastic Agents; D007987:Gonadotropin-Releasing Hormone; D016729:Leuprolide