Claims
- 1. A method for the treatment of a proliferative disease which comprises administering to a mammalian specie in need thereof a therapeutically effective amount of (1) a compound of formula I and (2) at least one anti-proliferative agent,
- 2. The method of claim 1 wherein the antiproliferative agent is administered after administration of the compound of formula I.
- 3. The method of claim 2 for the treatment of cancerous solid tumors.
- 4. The method of claim 2 for the treatment of refractory tumors.
- 5. The method of claim 1 wherein the anti-proliferative agent is selected from the group consisting of a microtubule affecting agent, an alkylating agent, an anti-metabolite, epidophyllotoxin, an antineoplastic enzyme, a topoisomerase inhibitor, procarbazine, mitoxantrone, inhibitors of cell cycle progression, radiation and a platinum coordination complex.
- 6. The method of claim 5 wherein the anti-proliferative agent is carboplatin.
- 7. The method of claim 1 wherein the compound of formula I is [1S-1R*,3R*(E),7R*,10S*,11R*,12R*,16S*]]-7,11-dihydroxy-8,8,10,12,16-pentamenthyl-3-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-4-aza-17-oxabicyclo[14.1.0]heptadecane-5,9-dione (Compound 1).
- 8. The method of claim 2 wherein the compound of formula I is [1S-1R*,3R*(E),7R*,10S*,11R*,12R*,16S*]]-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-4-aza-17-oxabicyclo[14.1.0]heptadecane-5,9-dione (Compound 1).
- 9. The method of claim 1 wherein the compound of formula I is [1S-1R*,3R*(E),7R*,10S*,11R*,12R*,16S*]]-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-4-aza-17-oxabicyclo[14.1.0]heptadecane-5,9-dione (Compound 1) and the anti-proliferative agent is carboplatin.
- 10. The method of claim 2 wherein the compound of formula I is [1S 1R*,3R*(E),7R*,10S*,11R*,12R*,16S*]]-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-4-aza-17-oxabicyclo[14.1.0]heptadecane-5,9-dione (Compound 1) and the anti-proliferative agent is carboplatin.
- 11. A method for modulating tumor growth in a human in need thereof, comprising sequential or simultaneous administration of [1S 1R*,3R*(E),7R*,10S*,11R*,12R*,16S*]]-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-4-aza-17-oxabicyclo[14.1.0]heptadecane-5,9-dione (Compound 1) and carboplatin.
- 12. The method of claim 11 wherein said [1S 1R*,3R*(E),7R*,10S*,11R*, 12R*,16S*]]-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-4-aza-17-oxabicyclo[14.1.0]heptadecane-5,9-dione (Compound 1) is administered first, followed by administration of carboplatin, and wherein this combination of Compound 1 and carboplatin is administered every three weeks for at least one treatment cycle.
- 13. The method of claim 12 wherein said [1S 1R*,3R*(E),7R*,10S*,11R*, 12R*,16S*]]-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-4-aza-17-oxabicyclo[14.1.0]heptadecane-5,9-dione (Compound 1) is administered as a 60-minute infusion, 30 minutes prior to a 30-minute infusion of carboplatin.
- 14. The method of claim 12 wherein the dosage of said [1S 1R*,3R*(E),7R*,10S*,11R*,12R*,16S*]]-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-4-aza-17-oxabicyclo[14.1.0]heptadecane-5,9-dione (Compound 1) is between 5 mg/m2 and 60 mg/m2 and the dosage of carboplatin is between 5 mg/m2 and 1000 mg/m2.
- 15. The method of claim 14 wherein the dosage of said [1S 1R*,3R*(E),7R*,10S*,11R*,12R*,16S*]]-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-4-aza-17-oxabicyclo[14.1.0]heptadecane-5,9-dione (Compound 1) is between 25 mg/m2 and 50 mg/m2 and the dosage of carboplatin is between 5 mg/m2 and 1000 mg/m2.
- 16. The method of claim 11 wherein said [1S 1R*, 3R*(E),7R*,10S*,11R*, 12R*, 16S*]]-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-4-aza-17-oxabicyclo[14.1.0]heptadecane-5,9-dione (Compound 1) is administered on day 1 and again on day 8, and carboplatin is administered on day 1, for at least one treatment cycle.
- 17. The method of claim 16 wherein said [1S 1R*,3R*(E),7R*,10S*,11R*, 12R*,16S*]]7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-4-aza-17-oxabicyclo[14.1.0]heptadecane-5,9-dione (Compound 1) is administered as a 60-minute infusion, 30 minutes prior to a 30-minute infusion of carboplatin.
- 18. The method of claim 16 wherein the dosage of said [1S 1R*,3R*(E),7R*,10S*,11R*,12R*,16S*]]-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-4-aza-17-oxabicyclo[14.1.0]heptadecane-5,9-dione (Compound 1) is between 5 mg/m2 and 60 mg/m2 and the dosage of carboplatin is between 5 mg/m2 and 1000 mg/m2.
- 19. The method of claim 18 wherein the dosage of said [1S 1R*,3R*(E),7R*,10S *,11R*,12R*,16S *]]-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-4-aza-17-oxabicyclo[14.1.0]heptadecane-5,9-dione (Compound 1) is between 15 and 30 mg/m2 and the dosage of carboplatin is between 5 mg/m2 and 1000 mg/m2.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority from provisional U.S. Application Serial No. 60/388,702, filed on Jun. 14, 2002, incorporated herein by reference in its entirety.
Provisional Applications (1)
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Number |
Date |
Country |
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60388702 |
Jun 2002 |
US |