Combination methods fo saha and targretin for treating cancer
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 SAHA or a pharmaceutically acceptable salt or hydrate thereof, and a second amount of Targretin. The SAHA and Targretin may be administered to comprise therapeutically effective amounts.
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 retinoid agent, 4-[1-(5,6,7,8-Tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)ethenyl]benzoic acid (3-methyl TTNEB) (Targretin), represented by the structure:
or a pharmaceutically acceptable salt or hydrate thereof, wherein the histone deacetylase inhibitor and the retinoid agent are administered in amounts effective for treating the cancer.
2 . The method of claim 1 , wherein the histone deacetylase inhibitor is administered prior to administering the retinoid agent.
3 . The method of claim 1 , wherein the histone deacetylase inhibitor and the retinoid agent are administered orally.
4 . The method of claim 3 , wherein the cancer is selected from the group consisting of a leukemia, a lymphoma, a myeloma, a sarcoma, a carcinoma, a solid tumor or any combination thereof.
5 . The method of claim 3 , wherein the cancer is a cutaneous T-cell lymphoma.
6 . The method of claim 5 , wherein SAHA is pre-administered I week prior to the concurrent administration of SAHA and Targretin.
7 . The method of claim 6 , wherein SAHA is administered 400 mg once a day in the pre-administration and concurrent administration.
8 . The method of claim 7 , wherein in the concurrent administration, Targretin is administered at 150 mg per day.
9 . The method of claim 7 , where the concurrent administration is for six 28-day cycles.
10 . The method of claim 6 , wherein in the concurrent administration of SAHA and Targretin, SAHA is administered 400 mg once a day for six 28-day cycles, Targretin is administered at 150 mg per day for the first 28-day cycle, and at 225 mg per day for the second to sixth 28-day cycle.
11 . The method of claim 6 , wherein in the concurrent administration of SAHA and Targretin, SAHA is administered 400 mg once a day for six 28-day cycles, Targretin is administered at 150 mg per day for the first 28-day cycle, at 225 mg per day for the second 28-day cycle, and at 300 mg per day for the third to sixth 28-day cycle.
12 . The method of claim 6 , wherein in the concurrent administration of SAHA and Targretin, SAHA is administered 400 mg once a day for six 28 day cycles, Targretin is administered at 150 mg per day for the first 28-day cycle, at 300 mg per day for the second 28-day cycle, and at 375 mg per day for the third to sixth 28-day cycle.
13 . The method of claim 6 , wherein in the concurrent administration of SAHA and Targretin, SAHA is administered 400 mg once a day for six 28-day cycles, Targretin is administered at 150 mg per day for the first 28-day cycle, at 300 mg per day for the second 28-day cycle, and at 450 mg per day for the third to sixth 28 day cycle.
14 . The method of claim 13 , wherein a lipid-lowering agent is administered during or before the pre-administration period, or a combination thereof.
15 . The method of claim 14 , wherein the lipid-lowering agent is fenofibrate.
16 . The method of claim 13 , wherein thyroxine is administered at the start of the concurrent administration period.
17 . The method of claim 16 , wherein the thyroxine is levothyroxine.
18 . A 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 retinoid agent, 4-[1-(5,6,7,8-Tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)ethenyl]benzoic acid (3-methyl TTNEB) (Targretin), represented by the structure:
or a pharmaceutically acceptable salt or hydrate thereof.
19 . The pharmaceutical composition of claim 18 , wherein the composition is formulated for oral administration.
20 . The pharmaceutical composition of claim 19 that comprises 100 mg of SAHA and 75 mg of Targretin.