Methods of using SAHA and Erlotinib for treating cancer

• US 20070197568A1
• Filed: 11/03/2006
• Published: 08/23/2007
• Est. Priority Date: 11/04/2005
• Status: Abandoned Application

• Current Assignee: Merck & Co., Inc., The Board of Regents of the University of Colorado (University of Colorado System)
• Original Assignee: The Board of Regents of the University of Colorado (University of Colorado System)
• Inventors: Bunn, Paul, Richon, Victoria, Frankel, Stanley, Deutsch, Paul, Randolph, Sophia, Witta, Samir
• Application Number:
  US11/592,443
• Publication Number:
  US 20070197568A1
• Time in Patent Office: Days
• US Class Current: 514/266.4
• 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 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention relates to a method of treating cancer in a subject in need thereof, by administering to a subject in need thereof a first amount of a histone deacetylase (HDAC) inhibitor such as suberoylanilide hydroxamic acid (SAHA), or a pharmaceutically acceptable salt or hydrate thereof, and a second amount of one or more anti-cancer agents, including Erlotinib. The HDAC inhibitor and the anti-cancer agent may be administered to comprise therapeutically effective amounts. In various aspects, the effect of the HDAC inhibitor and the anti-cancer agent may be additive or synergistic.

Claims

1. A method of treating cancer in a subject in need thereof comprising administering to the subject a histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), represented by the structure:

or a pharmaceutically acceptable salt or hydrate thereof, and a tyrosine kinase inhibitor, Erlotinib, represented by the structure;

or a pharmaceutically acceptable salt or hydrate thereof, wherein the histone deacetylase inhibitor and the tyrosine kinase inhibitor are administered in amounts effective for treating the cancer.

2. The method of claim 1, wherein the histone deacetylase inhibitor and the tyrosine kinase inhibitor are administered concurrently.

3. The method of claim 1, wherein the histone deacetylase inhibitor is administered prior to administering the tyrosine kinase inhibitor.

4. The method of claim 1, wherein the histone deacetylase inhibitor is administered after administering the tyrosine kinase inhibitor.

5. The method of claim 1, wherein the histone deacetylase inhibitor and the tyrosine kinase inhibitor are administered orally.

6. The method of any one of claims 1-5, wherein suberoylanilide hydroxamic acid (SAHA) and Erlotinib are administered.

7. The method of any one of claims 1-6, wherein the cancer is non-small cell lung cancer.

8. The method of any one of claims 1-7, wherein the histone deacetylase inhibitor is administered once daily at a dose of 300 mg, wherein the administration is continuous.

9. The method of any one of claims 1-7, wherein the histone deacetylase inhibitor is administered once daily at a dose of 200 mg for at least one period of 3 out of 7 days.

10. The method of any one of claims 1-7, wherein the histone deacetylase inhibitor is administered once daily at a dose of 300 mg for at least one period of 3 out of 7 days.

11. The method of any one of claims 1-7, wherein the histone deacetylase inhibitor is administered once daily at a dose of 400 mg for at least-one period of 3 out of 7 days.

12. The method of any one of claims 1-7, wherein the histone deacetylase inhibitor is administered once daily at a dose of 500 mg for at least one period of 3 out of 7 days.

13. The method of any one of claims 1-7, wherein the histone deacetylase inhibitor is administered twice daily at 200 mg per dose for at least one period of 3 out of 7 days.

14. The method of any one of claims 1-7, wherein the histone deacetylase inhibitor is administered twice daily at 300 mg per dose for at least one period of 3 out of 7 days.

15. The method of any one of claims 9-14, wherein the histone deacetylase inhibitor is administered for at least one period of 3 out of 7 days for two weeks, followed by a two-week rest period.

16. The method of any one of claims 9-14, wherein the histone deacetylase inhibitor is administered for at least one period of 3 out of 7 days for three weeks, followed by a one-week rest period.

17. The method of any one of claims 9-14, wherein the histone deacetylase inhibitor is administered for at least one period of 3 out of 7 days for one week, followed by a one-week rest period.

18. The method of any one of claims 1-7, wherein the histone deacetylase inhibitor is administered twice daily at 300 mg per dose for at least one period of 7 out of 14 days.

19. The method of any one of claims 1-7, wherein the histone deacetylase inhibitor is administered once daily at 300 mg per dose for at least one period of 14 out of 28 days.

20. The method of any one of claims 1-19, wherein the tyrosine kinase inhibitor is administered once daily at a dose of 50 mg, wherein the administration is continuous.

21. The method of any one of claims 1-19, wherein the tyrosine kinase inhibitor is administered once daily at a dose of 100 mg, wherein the administration is continuous.

22. The method of any one of claims 1-19, wherein the tyrosine kinase inhibitor is administered once daily at a dose of 150 mg, wherein the administration is continuous.

23. The method of any one of claims 1-7, wherein the histone deacetylase inhibitor is administered at a total daily dose of up to 400 mg and the tyrosine kinase inhibitor is administered at a total daily dose of up to 150 mg.

24. The method of any one of claims 1-7, wherein the histone deacetylase inhibitor is administered at a total daily dose of up to 600 mg and the tyrosine kinase inhibitor is administered at a total daily dose of up to 150 mg.

25. An oral pharmaceutical composition comprising a histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), represented by the structure:

or a pharmaceutically acceptable salt or hydrate thereof, and a tyrosine kinase inhibitor, Erlotinib, represented by the structure;

or a pharmaceutically acceptable salt or hydrate thereof, and optionally one or more pharmaceutically acceptable excipients.

26. The pharmaceutical composition of claim 25 that comprises about 100 mg of SAHA and about 50 mg of Erlotinib.

27. The pharmaceutical composition of claim 25, which comprises suberoylanilide hydroxamic acid (SAHA) and Erlotinib.