Claims
- 1. A method of treating diffuse large B-cell lymphoma in a subject, said method comprising the step of administering to the subject an effective amount of a pharmaceutical composition comprising a histone deacetylase (HDAC) inhibitor, or a pharmaceutically acceptable salt or hydrate thereof, and a pharmaceutically acceptable carrier or diluent, wherein the amount of histone deacetylase inhibitor is effective to treat diffuse large B-cell lymphoma in said subject.
- 2. The method of claim 1, wherein the HDAC inhibitor is suberoylanilide hydroxamic acid (SAHA), represented by the structure:
- 3. The method of claim 1, wherein the HDAC inhibitor is pyroxamide, represented by the structure:
- 4. The method of claim 1, wherein the HDAC inhibitor is represented by the structure:
- 5. The method of claim 1, wherein the HDAC inhibitor is represented by the structure:
- 6. The method of claim 1, wherein the HDAC inhibitor is represented by the structure:
- 7. The method of claim 1, wherein said HDAC inhibitor is a hydroxamic acid derivative, a Short Chain Fatty Acid (SCFA), a cyclic tetrapeptide, a benzamide derivative, or an electrophilic ketone derivative.
- 8. The method of claim 1, wherein said HDAC inhibitor is a hydroxamic acid derivative selected from the group consisting of SAHA, Pyroxamide, CBHA, Trichostatin A (TSA), Trichostatin C, Salicylhydroxamic Acid, Azelaic Bishydroxamic Acid (ABHA), Azelaic-1-Hydroxamate-9-Anilide (AAHA), 6-(3-Chlorophenylureido) carpoic Hydroxamic Acid (3Cl-UCHA), Oxamflatin, A-161906, Scriptaid, PXD-101, LAQ-824, CHAP, MW2796, and MW2996.
- 9. The method of claim 1, wherein said HDAC inhibitor is a cyclic tetrapeptide selected from the group consisting of Trapoxin A, FR901228 (FK 228 or Depsipeptide), FR225497, Apicidin, CHAP, HC-Toxin, WF27082, and Chlamydocin.
- 10. The method of claim 1, wherein said HDAC inhibitor is a Short Chain Fatty Acid (SCFA) selected from the group consisting of Sodium Butyrate, Isovalerate, Valerate, 4 Phenylbutyrate (4-PBA), Phenylbutyrate (PB), Propionate, Butyramide, Isobutyramide, Phenylacetate, 3-Bromopropionate, Tributyrin, Valproic Acid and Valproate.
- 11. The method of claim 1, wherein said HDAC inhibitor is a benzamide derivative selected from the group consisting of CI-994, MS-27-275 (MS-275) and a 3′-amino derivative of MS-27-275.
- 12. The method according to claim 1, wherein said HDAC inhibitor is an electrophilic ketone derivative selected from the group consisting of a trifluoromethyl ketone and an α-keto amide.
- 13. The method according to claim 1, wherein said HDAC inhibitor is a natural product, a psammaplin or Depudecin.
- 14. The method of claim 1, wherein the pharmaceutical composition is administered orally.
- 15. The method of claim 14, wherein said composition is contained within a gelatin capsule.
- 16. The method of claim 15, wherein said carrier or diluent is microcrystalline cellulose.
- 17. The method of claim 16, further comprising sodium croscarmellose as a disintegrating agent.
- 18. The method of claim 17, further comprising magnesium stearate as a lubricant.
- 19. The method of claim 14, wherein said composition is administered to the subject at a total daily dosage of between about 254000 mg/m2.
- 20. The method of claim 14, wherein said composition is administered once-daily, twice-daily or three times-daily.
- 21. The method of claim 20, wherein said composition is administered once daily at a dose of about 200-600 mg.
- 22. The method of claim 20, wherein said composition is administered twice daily at a dose of about 200-400 mg.
- 23. The method of claim 20, wherein said composition is administered twice daily at a dose of about 200-400 mg intermittently.
- 24. The method of claim 23, wherein said composition is administered three to five days per week.
- 25. The method of claim 23, wherein said composition is administered three days a week.
- 26. The method of claim 25, wherein said composition is administered at a dose of about 200 mg.
- 27. The method of claim 25, wherein said composition is administered at a dose of about 300 mg.
- 28. The method of claim 25, wherein said composition is administered at a dose of about 400 mg.
- 29. The method of claim 20, wherein said composition is administered three times daily at a dose of about 100-250 mg.
- 30. A method of treating diffuse large B-cell lymphoma in a subject, said method comprising the step of administering to the subject an effective amount of a pharmaceutical composition comprising suberoylanilide hydroxamic acid (SAHA) or a pharmaceutically acceptable salt or hydrate thereof, represented by the structure:
- 31. The method of claim 30, wherein the pharmaceutical composition is administered orally.
- 32. The method of claim 31, wherein said composition is contained within a gelatin capsule.
- 33. The method of claim 32, wherein said carrier or diluent is microcrystalline cellulose.
- 34. The method of claim 33, further comprising sodium croscarmellose as a disintegrating agent.
- 35. The method of claim 34, further comprising magnesium stearate as a lubricant.
- 36. The method of claim 31, wherein said composition is administered to the subject at a total daily dosage of between about 25-4000 mg/m2.
- 37. The method of claim 31, wherein said composition is administered once-daily, twice-daily or three times-daily.
- 38. The method of claim 37, wherein said composition is administered once daily at a dose of about 200-600 mg.
- 39. The method of claim 37, wherein said composition is administered twice daily at a dose of about 200-400 mg.
- 40. The method of claim 37, wherein said composition is administered twice daily at a dose of about 200-400 mg intermittently.
- 41. The method of claim 40, wherein said composition is administered three to five days per week.
- 42. The method of claim 40, wherein said composition is administered three days a week.
- 43. The method of claim 42, wherein said composition is administered at a dose of about 200 mg.
- 44. The method of claim 42, wherein said composition is administered at a dose of about 300 mg.
- 45. The method of claim 42, wherein said composition is administered at a dose of about 400 mg.
- 46. The method of claim 37, wherein said composition is administered three times daily at a dose of about 100-250 mg.
- 47. A method of treating diffuse large B-cell lymphoma in a subject, said method comprising the step of administering to the subject a total daily dose of up to about 800 mg of a pharmaceutical composition comprising suberoylanilide hydroxamic acid (SAHA) or a pharmaceutically acceptable salt or hydrate thereof, represented by the structure:
- 48. The method of claim 47, wherein the pharmaceutical composition is administered orally.
- 49. The method of claim 48, wherein said composition is contained within a gelatin capsule.
- 50. The method of claim 49, wherein said carrier or diluent is microcrystalline cellulose.
- 51. The method of claim 50, further comprising sodium croscarmellose as a disintegrating agent.
- 52. The method of claim 51, further comprising magnesium stearate as a lubricant.
- 53. The method of claim 48, wherein said composition is administered once-daily, twice-daily or three times-daily.
- 54. The method of claim 53, wherein said composition is administered once daily at a dose of about 200-600 mg.
- 55. The method of claim 53, wherein said composition is administered twice daily at a dose of about 200-400 mg.
- 56. The method of claim 53, wherein said composition is administered twice daily at a dose of about 200-400 mg intermittently.
- 57. The method of claim 56, wherein said composition is administered three to five days per week.
- 58. The method of claim 56, wherein said composition is administered three days a week.
- 59. The method of claim 58, wherein said composition is administered at a dose of about 200 mg.
- 60. The method of claim 58, wherein said composition is administered at a dose of about 300 mg.
- 61. The method of claim 58, wherein said composition is administered at a dose of about 400 mg.
- 62. The method of claim 53, wherein said composition is administered three times daily at a dose of about 100-250 mg.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. application Ser. No. 10/379,149, filed on Mar. 4, 2003, which claims the benefit of U.S. Provisional Application No. 60/361,759, filed Mar. 4, 2002. The entire teachings of these applications are incorporated herein by reference.
GOVERNMENT INTEREST STATEMENT
[0002] This invention was made in whole or in part with government support under grant number 1R21 CA 096228-01 awarded by the National Cancer Institute. The government may have certain rights in the invention.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60361759 |
Mar 2002 |
US |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
10379149 |
Mar 2003 |
US |
Child |
10665079 |
Sep 2003 |
US |