Patent EA-002525-B1 (EA)
Title: Combination of tyrosine kinase inhibitor and chemical castration to treat prostate cancer
Inventor: DIONNE Craig
IPC: A61K38/04
Filed: 1998-08-13
Abstract: 1. A method for inhibiting prostate tumor progression in a mammal, comprising administering a therapeutically effective amount of a tyrosine kinase inhibitor selected from the group, comprising a trkA inhibitor, a trkS inhibitor, or a trkC inhibitor and co-administering to the mammal a therapeutically effective amount of a chemical castration agent selected from the group consisting of an estrogen, arx LHRH agonist, an LHRH antagonist, and an antiandrogen. 2. The method of claim 1, wherein the mammal is a human. 3. The method of claim 1 wherein the therapeutically effective amount of a tyrosine kinase inhibitor and the therapeutically effective amount of the chemical castration agent inhibit tumor progression synergistically. 4. The method of claim 1, wherein the tyrosine kinase inhibitor is an indolocarbazole. 5. The method of claim 4, wherein the indolocarbazole has the following structure:   6. The method of claim 4, wherein the indolocarbazole has the following structure:   7. The method of claim 4, wherein the indolocarbazole has the following structure:   8. The method of claim 1, wherein the tyrosine kinase inhibitor is a fused pyrrolocarbazole. 9. The method of claim 1, wherein the tyrosine kinase inhibitor is administered orally. 10. The method of claim 1, wherein the tyrosine kinase inhibitor is administered parenterally. 11. The method of claim 1, wherein the LHRH agonist is leuprolide acetate. 12. The method of claim 1, wherein the antiandrogen is flutamide. 13. The method of claim 1, wherein the chemical castration agent is a combination of an LHRH agonise and an antiandrogen. 14. The method of claim 13, wherein the LHRH agonist is leuprolide acetate, and the antiandrogen is flutamide. 15. The method of claim 1, wherein the tyrosine kinase inhibitor and the chemical castration agent are administered in separate formulations. 16. The method of Claim 1, wherein the tyrosine kinase inhibitor and the chemical castration agent are formulated together in a single composition. 17. A ccampcsition comprising a tyrosine kinase inhibitor selected from the group, comprising a trkA inhibitor, a trkS inhibitor, or a trkC inhibitor and a chemical castration agent selected from the group consisting of an estrogen, an LHRH agonist, an LHRH antagonist, and an antiandrogen. 18. The composition of claim 17, wherein the tyrosine kinase inhibitor is an indolocarbazole. 19. The composition cf claim 18, wherein the indolocarbazole is selected from the group consisting of: an indolocarbazole having the following structure:   the indolocarbazole having the following structure:   and the having the following structure:   20. The composition of claim 17, wherein the tyrosine kinase inhibitor is a fused pyrrolocarbazole. 21. The composition of claim 17, wherein the tyrosine kinase inhibitor is administered orally. 22. The composition of claim 17, wherein the tyrosine kinase inhibitor is administered parenterally. 23. The composition of claim 17, wherein the LHRH agonist is leuprolide acetate. 24. The composition of claim 17, wherein the antiandrogen is flutamide. 25. The composition of claim 17, wherein the chemical castration agent is a combination of an LHRH agonise and an antiandrogen. 26. The composition of claim 17, wherein the LHRH agonist is leuprolide acetate, and the antiandrogen is flutamide.