Combination of epothilone analogs and chemotherapeutic agents for the treatment of proliferative diseases

• US 7,008,936 B2
• Filed: 06/12/2003
• Issued: 03/07/2006
• Est. Priority Date: 06/14/2002
• Status: Active Grant

• Current Assignee: Huma Therapeutics Ltd.
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Lebwohl, David, Voi, Maurizio
• Primary Examiner(s): Henley, III, Raymond J.
• Application Number:
  US10/459,972
• Publication Number:
  US 20040024032A1
• Time in Patent Office: 999 Days
• Field of Search: 514/183, 514/203, 514/210.02, 514/291, 514/365, 514/450, 514/492
• US Class Current: 514/184
• 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 31/282 Platinum compounds
• CPC Class Codes: A61K 31/33 Heterocyclic compounds
• CPC Class Codes: A61K 31/335 having oxygen as the only ring hetero atom, e.g. fungichromin
• CPC Class Codes: A61K 31/425 Thiazoles
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

Compositions and methods are disclosed which are useful of the treatment and prevention of proliferative diseases.

Claims

1. A method of treating cancer in a patient comprising administering to the patient the compound which is [1S1R*,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), wherein Compound 1 is administered in a split dose, first on day 1 and then again on day 8, and carboplatin is administered on day 1, for at least one treatment cycle, wherein the cancer is selected from bladder cancer, pancreatic cancer, prostate cancer, lung cancer, colorectal cancer and breast cancer.

2. The method of claim 1 wherein said dose of [1S1R*,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) on day 1 is administered as a 60-minute infusion, 30 minutes prior to a 30-minute infusion of carboplatin.

3. The method of claim 1 wherein the dosage of said [1S1R*,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-oxabicyclol[14.1.0]heptadecane-5,9-dione (Compound 1) on day 1 and/or day 8 is between 5 mg/m² and 60 mg/m² and the dosage of carboplatin is between 5 mg/m² and 1000 mg/m².

4. The method of claim 3 wherein the dosage of said [1S1R*,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) on day 1 and/or day 8 is between 15 and 30 mg/m² and the dosage of carboplatin is between 5 mg/m² and 1000 mg/m².

5. The method of claim 1, wherein the cancer is breast cancer.

6. The method of claim 1, wherein the cancer is non small-cell lung cancer.

7. The method of claim 1, wherein the cancer is prostate cancer.

8. A method of treating cancer in a patient comprising administering to the patient the compound which is [1S1R*,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), wherein Compound 1 is administered in a split dose, first on day 1 and then again on day 8, and carboplatin is administered on day 1, for at least one treatment cycle, wherein the cancer is refractory to taxane treatment.