Patent EA-003466-B1 (EA)
Title: A method for chemoprevention of prostate cancer
Inventor: STEINER MITCHELL S
IPC: A61K31/135
Filed: 1999-05-07
Abstract: 1. A method for preventing prostate carcinogenesis comprising: administering to a mammalian subject a pharmaceutical preparation comprising a chemopreventive agent having the formula: wherein R1 and R2, which can be the same or different, are H or OH; R3 is OCH2CH2NR4R5, wherein R4 and R5, which can be the same or different, are H or an alkyl group of 1 to about 4 carbon atoms; and their pharmaceutically acceptable salts, esters, or N-oxides, and mixtures thereof. 2. The method according to claim 1, wherein said pharmaceutical preparation further comprises a pharmaceutically acceptable carrier. 3. The method according to claim 2, wherein said carrier is selected from the group consisting of a gum, a starch, a sugar, a cellulosic material and mixtures thereof. 4. The method according to claim 1, wherein said administering comprises: subcutaneously implanting in said subject a pellet containing said pharmaceutical preparation. 5. The method according to claim 4, wherein said pellet provides for controlled release of said pharmaceutical preparation over a period of time. 6. The method according to claim 1, wherein said administering intravenously, intraarterially, or intramuscularly injecting in said subject said pharmaceutical preparation in liquid form. 7. The method according to claim 1, wherein said administering orally administering to said subject a liquid or solid preparation containing said pharmaceutical preparation. 8. The method according to claim 1, wherein said administering topically applying to skin surface of said subject said pharmaceutical preparation. 9. The method according to claim 1, wherein said pharmaceutical preparation is selected from the group consisting of a pellet, a tablet, a capsule, a solution, a suspension, an emulsion, an elixir, a gel, a cream, and a suppository. 10. The method according to claim 9, wherein said suppository is a rectal suppository or a urethral suppository. 11. The method according to claim 1, wherein said pharmaceutical preparation is a parenteral formulation. 12. The method according to claim 11, wherein said parenteral formulation comprises a liposome comprising a complex of said chemopreventive agent and a cyclodextrin compound. 13. The method according to claim 1, wherein said chemopreventive agent comprises toremifene, its N-oxide, pharmaceutically acceptable salts, and mixtures thereof. 14. The method according to claim 1, wherein said administering is carried out at a dosage of about 0.5 mg/kg of subject weight/day to about 50 mg/kg of subject weight/day of said chemopreventive agent. 15. The method according to claim 14, wherein said administering is carried out at about 6 mg/kg of subject weight/day to about 30 mg/kg of subject weight/day of said chemopreventive agent. 16. The method according to claim 1, wherein said subject has an elevated risk of prostate cancer. 17. The method according to claim 16, wherein said subject has benign prostatic hyperplasia, prostatic intraepithelial neoplasia (PIN), or an abnormally high level of circulating prostate specific antibody (PSA). 18. A method for preventing the recurrence of, suppressing or inhibiting prostate carcinogenesis, or increasing the survival rate of a subject having prostate cancer comprising: administering to a mammalian subject a pharmaceutical preparation comprising a chemopreventive agent having the formula: wherein R1 and R2, which can be the same or different, are H or OH; R3 is OCH2CH2NR4R5, wherein R4 and R5, which can be the same or different, are H or an alkyl group of 1 to about 4 carbon atoms; and their pharmaceutically acceptable salts, esters, or N-oxides, and mixtures thereof. 19. Use the compound of formula (I) wherein R1 and R2, which can be the same or different, are H or OH; R3 is OCH2CH2NR4R5, wherein R4 and R5, which can be the same or different, are H or an alkyl group of 1 to about 4 carbon atoms; and their pharmaceutically acceptable salts, esters, or N-oxides, and mixtures thereof, in preparing pharmaceutical compositions for use in method of suppressing or inhibiting precancerous precursors of prostate adenocarcinoma. 20. Use according to claim 19, wherein the precancerous precursor or prostate adenocarcinoma is prostate intraepithelial neoplasia (PIN). 21. Use according to claim 20, wherein prostate intraepithelial neoplasia is high prostate intraepithelial neoplasia (HPIN). 22. Use the compound of formula (I) wherein R1 and R2, which can be the same or different, are H or OH; R3 is OCH2CH2NR4R5, wherein R4 and R5, which can be the same or different, are H or an alkyl group of 1 to about 4 carbon atoms; and their pharmaceutically acceptable salts, esters, or N-oxides, and mixtures thereof, in preparing pharmaceutical compositions for use in method of treating or inhibiting precancerous precursors of prostate adenocarcinoma. 23. Use according to claim 22, wherein the precancerous precursor or prostate adenocarcinoma is prostate intraepithelial neoplasia (PIN). 21. Use according to claim 22, wherein prostate intraepithelial neoplasia is high prostate intraepithelial neoplasia (HPIN).