Low dose combination CDA substrate drug/cedazuridine with extended administration
This invention relates to methods and compositions for administering an effective amount of a CDA substrate drug and an effective amount of cedazuridine. In particular, the invention relates to methods for treating cancer, inhibiting degradation of a CDA substrate drug, and reducing DNA methylation in a subject in need thereof comprising administering an effective amount of a CDA substrate drug and an effective amount of cedazuridine.
1. A method for inhibiting degradation of a cytidine deaminase (CDA) substrate drug in a subject in need thereof, comprising administering to the subject:
(i) an effective amount of a CDA substrate drug, wherein when the CDA substrate drug is decitabine, the effective amount of decitabine is from about 5 mg per dose to about 15 mg per dose; and
(ii) an effective amount of cedazuridine,
thereby inhibiting degradation of the CDA substrate drug in the subject.
2. The method of claim 1 , wherein the administering of (i) is concurrent with the administering of (ii).
3. The method of claim 2 , wherein the administering is performed in one composition.
4. The method of claim 1 , wherein the administering of (i) is performed prior to the administering of (ii).
5. The method of claim 1 , wherein the administering of (ii) is performed prior to the administering of (i).
6. The method of claim 1 , wherein the administering steps (i) and (ii) are performed about 1 day to about 28 days per 28-day cycle.
7. The method of claim 1 , wherein the administering steps (i) and (ii) are performed on consecutive days per 28-day cycle.
8. The method of claim 1 , wherein the administering steps (i) and (ii) are performed on non-consecutive days per 28-day cycle.
9. The method of claim 1 , wherein the CDA substrate drug is decitabine.
10. The method of claim 1 , wherein the CDA substrate drug is 5-azacytidine.
11. The method of claim 9 , wherein the effective amount of decitabine is from about 15 mg to about 75 mg cumulative per 28-day cycle of treatment.
12. The method of claim 10 , wherein the effective amount of 5-azacytidine is from about 10 mg per dose to about 450 mg per dose.
13. The method of claim 10 , wherein the effective amount of 5-azacytidine is from about 10 mg to about 3500 mg cumulative per 28-day cycle of treatment.
14. The method of claim 1 , wherein the effective amount of cedazuridine is from about 40 mg per dose to about 1000 mg per dose.
15. The method of claim 14 , wherein the effective amount of cedazuridine is about 100 mg per dose.
16. The method of claim 1 , wherein the effective amount of cedazuridine is from about 100 mg to about 7000 mg cumulative per 28-day cycle of treatment.
17. The method of claim 1 , wherein the CDA substrate drug and cedazuridine are administered intravenously, orally, or subcutaneously.
18. The method of claim 1 , wherein the subject is a mammal.
19. The method of claim 18 , wherein the subject is a human.