Methods for preparation and use of 1alpha,24(S)-dihydroxyvitamin D2

• US 20040009958A1
• Filed: 03/18/2003
• Published: 01/15/2004
• Est. Priority Date: 01/08/1991
• Status: Abandoned Application

• Current Assignee: Bone Care International Inc (Sanofi )
• Original Assignee: Bone Care International Inc (Sanofi )
• Inventors: Bishop, Charles W., Mazess, Richard B., Knutson, Joyce C., Strugnell, Stephen
• Application Number:
  US10/390,953
• Publication Number:
  US 20040009958A1
• Time in Patent Office: Days
• US Class Current: 514/167
• 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 31/047 having two or more hydroxy groups, e.g. sorbitol
• CPC Class Codes: A61K 31/59 Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
• CPC Class Codes: A61K 31/592 9,10-Secoergostane derivatives, e.g. ergocalciferol, i.e. vitamin D2
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07C 401/00 Irradiation products of cholesterol or its derivatives; Vitamin D derivatives, 9,10-seco cyclopenta[a]phenanthrene or analogues obtained by chemical preparation without irradiation
• CPC Class Codes: C07J 71/0042 Nitrogen only
• CPC Class Codes: C07J 9/00 Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane

Abstract

A method of inhibiting the hyperproliferation of malignant or neoplastic cells, comprising treating the cells with an antiproliferative amount of 1α,24(S)-dihydroxyvitamin D₂. The method also includes the co-administration of cyotoxic agents with the 1α,24(S)-dihydroxyvitamin D₂.

Claims

1. A method of inhibiting hyperproliferation of malignant or neoplastic cells, comprising treating the cells with an antiproliferative amount of 1α

,24(S)-dihydroxyvitamin D₂, the cells being cancers of acute lymphobalstic leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia and plasma cell dyscrasias.

22. The method of claim 1, wherein the plasma cell dyscrasia is selected from the group consisting of Waldenströ

m'"'"'s macroglobulinemia, heavy chain diseases, benign monoclonal gammopathy, and immunocytic amyloidosis.

25. The method of claim 22 wherein the plasma cell dyscrasia is Waldenströ

m'"'"'s macroglobulinemia.

26. The method of claim 22 wherein the plasma cell dyscrasia is a heavy chain disease.

27. The method of claim 22 wherein the plasma cell dyscrasia is benign monoclonal gammopathy.

28. The method of claim 22 wherein the plasma cell dyscrasia is immunocytic amyloidosis.

37. The method of claim 1 wherein the cancer is acute lymphobalstic leukemia.

38. The method of claim 1 wherein the cancer is acute myelogenous leukemia.

39. The method of claim 1 wherein the cancer is chronic lymphocytic leukemia.

40. The method of claim 1 wherein the cancer is chronic myelogenous leukemia.

2. A method of inhibiting the hyperproliferative activity of malignant or neoplastic cells, comprising administering to a patient suffering therefrom, an antiproliferative amount of 1α

,24(S)-dihydroxyvitamin D₂, the cells being cancers of acute lymphobalstic leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia and plasma cell dyscrasias.

3. A method in accordance with claim 2, wherein 1α

,24(S)-dihydroxyvitamin D₂ is administered in a daily dosing regimen or an episodic dosing regimen.

4. A method in accordance with claim 3, wherein the episodic regimen is a dose once every 2 to 7 days.

5. A method in accordance with claim 3, wherein the 1α

,24(S)-dihydroxyvitamin D₂ is administered daily at a dose of about 1 to 100 μ

g/day.

6. A method in accordance with claim 2, wherein the 1α

,24(S)-dihydroxyvitamin D₂ is administered orally, is administered intravenously, is direct injected into a cancer site or is regionally delivered to a cancer site.

7. A method in accordance with claim 6, wherein the 1α

,24(S)-dihydroxyvitamin D₂ is administered orally.

8. A method in accordance with claim 2, wherein the 1α

,24(S)-dihydroxyvitamin D₂ is co-administered with a cytotoxic agent.

9. A method in accordance with claim 8, wherein the cytotoxic agent is an antimetabolite, and antimicrotubule agent, an alkyating agent, a platinum agent, an anthracycline, a topoisomase inhibitor, or an antibiotic.

10. A method in accordance with claim 9, wherein the antimetabolite is 5-fluoro-uracil, methotrexate or fludarabine.

11. A method in accordance with claim 9, wherein the antimicrotubule agent is vincristine, vinblastine or a taxane.

12. A method in accordance with claim 11, wherein the taxane is paclitaxel or docetaxel.

13. A method in accordance with claim 9, wherein the alkylating agent is cyclophasphamide, melphalan, biochoroethylnitrosurea or hydroxyurea.

14. A method in accordance with claim 9, wherein the platinum agent is cisplatin, carboplatin, oxaliplatin, JM-216 or CI-973.

15. A method in accordance with claim 9, wherein the anthracycline is doxrubicin or daunorubicin.

16. A method in accordance with claim 9, wherein the antibiotic is mitomycin, idarubicin, adriamycin or daunomycin.

17. A method in accordance with claim 9, wherein the topoisomerase inhibitor is etoposide or camptothecins.

18. A method in accordance with claim 9 wherein the cytotoxic agent is estramustine phosphate or prednimustine.

19. A method in accordance with claim 8, wherein antiproliferative effective amount of the cytotoxic agent is lower than the antiproliferative effective amount of the cytotoxic agent when administered alone.

23. The method of claim 2, wherein the plasma cell dyscrasia is selected from the group consisting of Waldenströ

m'"'"'s macroglobulinemia, heavy chain diseases, benign monoclonal gammopathy, and immunocytic amyloidosis.

29. The method of claim 23 wherein the plasma cell dyscrasia is Waldenströ

m'"'"'s macroglobulinemia.

30. The method of claim 23 wherein the plasma cell dyscrasia is a heavy chain disease.

31. The method of claim 23 wherein the plasma cell dyscrasia is benign monoclonal gammopathy.

32. The method of claim 23 wherein the plasma cell dyscrasia is immunocytic amyloidosis.

41. The method of claim 2 wherein the cancer is acute lymphobalstic leukemia.

42. The method of claim 2 wherein the cancer is acute myelogenous leukemia.

43. The method of claim 2 wherein the cancer is chronic lymphocytic leukemia.

44. The method of claim 2 wherein the cancer is chronic myelogenous leukemia.

45. A method in accordance with claim 2, wherein the 1α

,24(S)-dihydroxyvitamin D₂ is co-administered with a differentiation agent.

46. The method of claim 45 wherein the differentiation agent is include all-trans retinoic acid.

47. A method in accordance with claim 2, wherein the 1α

,24(S)-dihydroxyvitamin D₂ is co-administered with an angiogenesis inhibiting agent.

48. The method of claim 47 wherein the angiogenesis inhibiting agent is melphalan.

49. The method of claim 47 wherein the angiogenesis inhibiting agent is prednisone.

50. The method of claim 47 wherein the angiogenesis inhibiting agent is thalidomide.

51. A method in accordance with claim 2, wherein the 1α

,24(S)-dihydroxyvitamin D₂ is co-administered with a biomodulating agent.

52. The method of claim 51 wherein the biomodulating agent is an antibody, a monoclonal antibody, a vaccines, a colony stimulating factors (CSF) or a cytokine.

53. The method of claim 52 wherein the biomodulating agent is a monoclonal antibody.

54. The method of claim 53 wherein the monoclonal antibody is Rituximab.

55. The method of claim 53 wherein the monoclonal antibody is Trastuzumab.

20. A method of treating a human to alleviate the pathological effects of acute lymphobalstic leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, plasma cell dyscrasias, and myelodysplastic syndromes, comprising administering to the human an effective amount of 1α

,24(S)-dihydroxyvitamin D₂.

24. The method of claim 20, wherein the plasma cell dyscrasia is selected from the group consisting of Waldenströ

m'"'"'s macroglobulinemia, heavy chain diseases, benign monoclonal gammopathy, and immunocytic amyloidosis.

33. The method of claim 24 wherein the plasma cell dyscrasia is Waldenstrim'"'"'s macroglobulinemia.

34. The method of claim 24 wherein the plasma cell dyscrasia is a heavy chain disease.

35. The method of claim 24 wherein the plasma cell dyscrasia is benign monoclonal gammopathy.

36. The method of claim 24 wherein the plasma cell dyscrasia is immunocytic amyloidosis.

21. A method of inducing differentiation in a patient suffering from a myelodysplastic syndrome, comprising treating the cells with a prodifferentiative amount of 1α

,24(S)-dihydroxyvitamin D₂.