COMBINATION THERAPY WITH A PROTEASOME INHIBITOR AND A GALLIUM COMPLEX

1 . A method of treating proliferative disorder, comprising

administering, simultaneously or sequentially, to a patient in need of the treatment a therapeutically effective amount of a compound of Formula (I)

wherein R 1 represents hydrogen, a halogen or a sulfono group SO 3 M, in which M is a metal ion, and R 2 represents hydrogen, or R 1 is Cl and R 2 is I, or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of a proteasome inhibitor.

2 . The method of claim 1 , wherein said compound of Formula (I) is tris(8-quinolinolato)gallium(III).

3 . The method of claim 2 , wherein the proteasome inhibitor is bortezomib.

4 . The method of claim 2 , wherein the proteasome inhibitor is chosen from the group of [(1R)-1-({[(2,3-difluorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid, [(1R)-1-({[(5-chloro-2-fluorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid, [(1R)-1-({[(3,5-difluorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid, [(1R)-1-({[(2,5-difluorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid, [(1R)-1-({[(2-bromobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid, [(1R)-1-({[(2-fluorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid, [(1R)-1-({[(2-chloro-5-fluorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid, [(1R)-1-({[(4-fluorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid, [(1R)-1-({[(3,4-difluorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid, [(1R)-1-({[3-chlorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid, [(1R)-1-({[(2,5-dichlorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid, [(1R)-1-({[(3,4-dichlorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid, [(1R)-1-({[(3-fluorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid, [(1R)-1-({[(2-chloro-4-fluorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid, [(1R)-1-({[(2,3-dichlorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid, [(1R)-1-({[(2-chlorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid, [(1R)-1-({[(2,4-difluorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid, [(1R)-1-({[(4-chloro-2-fluorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid, [(1R)-1-({[(4-chlorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid, [(1R)-1-({[(2,4-dichlorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid, and [(1R)-1-({[(3,5-dichlorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid, and mannitol esters, salts and boronic acid anhydride thereof.

5 . The method of claim 2 , wherein the proteasome inhibitor is CEP-18770, carfilzomib or MLN9708.

6 . The method of claim 2 , wherein the disease is cancer.

7 . The method of claim 2 , wherein the disease is multiple myeloma.

8 . The method of claim 2 , wherein the disease is a solid tumor.

9 . The method of claim 2 , wherein the disease is a hematological cancer.

10 . A kit, comprising in a compartmentalized container:

a first unit dosage form having a compound of Formula (I)

wherein R 1 represents hydrogen, a halogen or a sulfono group SO 3 M, in which M is a metal ion, and R 2 represents hydrogen, or R 1 is Cl and R 2 is I, or a pharmaceutically acceptable salt thereof; and

a second unit dosage form having a proteasome inhibitor.

11 . The kit of claim 10 , wherein the compound of Formula (I) is tris(8-quinolinolato)gallium(III).

12 . The kit of claim 11 , wherein the proteasome inhibitor is bortezomib.

13 . A pharmaceutical composition, comprising a therapeutically effective amount of a compound of Formula (I)

wherein R 1 represents hydrogen, a halogen or a sulfono group SO 3 M, in which M is a metal ion, and R 2 represents hydrogen, or R 1 is Cl and R 2 is I, or a pharmaceutically acceptable salt thereof and a proteasome inhibitor.

14 . The pharmaceutical composition of claim 13 , wherein said compound of Formula (I) is tris(8-quinolinolato)gallium(III).

15 . The pharmaceutical composition of claim 14 , wherein the proteasome inhibitor is bortezomib.