Methods for treating LHRH associated disorders with LHRH antagonists

• US 6,211,153 B1
• Filed: 11/11/1999
• Issued: 04/03/2001
• Est. Priority Date: 12/15/1995
• Status: Expired due to Fees

• Current Assignee: Praecis Pharmaceuticals, Inc. (GlaxoSmithKline PLC)
• Original Assignee: Praecis Pharmaceuticals, Inc. (GlaxoSmithKline PLC)
• Inventors: Garnick, Marc B., Molineaux, Christopher J., Gefter, Malcolm L.
• Primary Examiner(s): Raymond, Richard L.
• Application Number:
  US09/438,718
• Time in Patent Office: 509 Days
• Field of Search: 514/15, 514/2, 514/16, 514/429, 514/522, 514/629, 514/800, 530/328
• US Class Current: 514/10.3
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/09 Luteinising hormone-releasing hormone [LHRH] , i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 5/04 for decreasing, blocking or antagonising the activity of the hypothalamic hormones
• CPC Class Codes: A61P 5/36 Antigestagens

Abstract

Methods for treating prostate cancer are disclosed. The methods of the invention generally feature administration to a subject of an LHRH-R antagonist, in combination with a second therapy. In one embodiment, this second therapy is performance of a procedure that removes or destroys prostatic tumor tissue, such as a radical prostatectomy, cryosurgery or X-ray therapy (external or interstitial). In another embodiment, the second therapy is treatment with an LHRH-R agonist, either simultaneous with or subsequent to LHRH-R antagonist therapy. The methods of the invention can further involve administering an antiandrogen and/or an inhibitor of sex steroid biosynthesis to the subject in combination with the LHRH-R antagonist.

Claims

1. A method for treating ovarian cancer in a subject in need of such treatment, comprising:

administering to the subject an LHRH antagonist; and

performing a procedure on the subject that removes or destroys ovarian tumor tissue.

2. The method of claim 1, wherein the LHRH antagonist is administered to the subject prior to performing the procedure that removes or destroys ovarian tumor tissue.

3. The method of claim 1, wherein the LHRH antagonist is administered for about 3 to 6 months prior to performing the procedure that removes or destroys ovarian tumor tissue.

4. The method of claim 1, wherein the LHRH antagonist is administered for about 6 to 12 months prior to performing the procedure that removes or destroys ovarian tumor tissue.

5. The method of claim 1, wherein administration of the LHRH antagonist to the subject is continued after performing the procedure that removes or destroys ovarian tumor tissue.

26. The method of any one of claims 1, 6, 11, 16, or 21, wherein the procedure that removes or destroys tissue is selected from the group consisting of radical excision, cryosurgery, external radiation therapy and interstitial radiation therapy.

27. The method of any one of claims 1, 6, 11, 16, or 21, wherein the LHRH antagonist has an ED₅₀ for histamine release in a standard in vitro histamine release assay of at least 3 μ

g/ml.

28. The method of any one of claims 1, 6, 11, 16 or 21, wherein the LHRH antagonist has an ED₅₀ for histamine release in a standard in vitro histamine release assay of at least 5 μ

g/ml.

29. The method of any one of claims 1, 6, 11, 16, or 21, wherein the LHRH antagonist has an ED₅₀ for histamine release in a standard in vitro histamine release assay of at least 10 μ

g/ml.

30. The method of any one of claims 1, 6, 11, 16, or 21, further comprising administering to the subject at least one inhibitor of sex steroid biosynthesis in combination with the LHRH antagonist prior to performing the procedure that removes or destroys the tissue.

31. The method of any one of claims 1, 6, 11, 16, or 21, wherein the LHRH antagonist has the following structure:

Ac-D-Nal-4-Cl-D-Phe-D-Pal-Ser-N-Me-Tyr-D-Asn-Leu-Lys(iPr)-Pro-D-Ala-NH₂.

32. The method of any one of claims 1, 6, 11, 16 or 21, wherein the LHRH antagonist has the following structure:

Ac-D-Nal-4-Cl-D-Phe-f)-Pal-Ser-Tyr-D-Asn-Leu-Lys(iPr)-Pro-D-Ala-NH₂.

33. The method of any one of claims 1, 6, 11, 16, or 21, wherein the LHRH antagonist comprises the structure:

6. A method for treating breast cancer in a subject in need of such treatment, comprising:

administering to the subject an LHRH antagonist; and

performing a procedure on the subject that removes or destroys breast tumor tissue.

7. The method of claim 6, wherein the LHRH antagonist is administered to the subject prior to performing the procedure that removes or destroys breast tumor tissue.

8. The method of claim 6, wherein the LHRH antagonist is administered for about 3 to 6 months prior to performing the procedure that removes or destroys breast tumor tissue.

9. The method of claim 6, wherein the LHRH antagonist is administered for about 6 to 12 months prior to performing the procedure that removes or destroys breast tumor tissue.

10. The method of claim 6, wherein administration of the LHRH antagonist to the subject is continued after performing the procedure that removes or destroys breast tumor tissue.

11. A method for treating uterine fibroids in a subject in need of such treatment, comprising:

administering to the subject an LHRH antagonist; and

performing a procedure on the subject that removes or destroys uterine fibroid tissue.

12. The method of claim 11, wherein the LHRH antagonist is administered to the subject prior to performing the procedure that removes or destroys uterine fibroid tissue.

13. The method of claim 11, wherein the LHRH antagonist is administered for about 3 to 6 months prior to performing the procedure that removes or destroys uterine fibroid tissue.

14. The method of claim 11, wherein the LHRH antagonist is administered for about 6 to 12 months prior to performing the procedure that removes or destroys uterine fibroid tissue.

15. The method of claim 11, wherein administration of the LHRH antagonist to the subject is continued after performing the procedure that removes or destroys uterine fibroid tissue.

16. A method for treating benign prostatic hypertrophy in a subject in need of such treatment, comprising:

administering to the subject an LHRH antagonist; and

performing a procedure on the subject that removes or destroys hypertrophic prostatic tissue.

17. The method of claim 16, wherein the LHRH antagonist is administered to the subject prior to performing the procedure that removes or destroys hypertrophic prostatic tissue.

18. The method of claim 16, wherein the LHRH antagonist is administered for about 3 to 6 months prior to performing the procedure that removes or destroys hypertrophic prostatic tissue.

19. The method of claim 16, wherein the LHRH antagonist is administered for about 6 to 12 months prior to performing the procedure that removes or destroys hypertrophic prostatic tissue.

20. The method of claim 16, wherein administration of the LHRH antagonist to the subject is continued after performing the procedure that removes or destroys hypertrophic prostatic tissue.

21. A method for treating endometriosis in a subject in need of such treatment, comprising:

administering to the subject an LHRH antagonist; and

performing a procedure on the subject that removes or destroys endometrial tissue.

22. The method of claim 21, wherein the LHRH antagonist is administered to the subject prior to performing the procedure that removes or destroys endometrial tissue.

23. The method of claim 21, wherein the LHRH antagonist is administered for about 3 to 6 months prior to performing the procedure that removes or destroys endometrial tissue.

24. The method of claim 21, wherein the LHRH antagonist is administered for about 6 to 12 months prior to performing the procedure that removes or destroys endometrial tissue.

25. The method of claim 21, wherein administration of the LHRH antagonist to the subject is continued after performing the procedure that removes or destroys endometrial tissue.