Cancer therapy
A method of treating haematological cancer with a therapy comprising a DHODH inhibitor. Also provided is a combination therapy comprising a pan-HER inhibitor and a DHODH inhibitor for treating a haematological cancer.
1. A method of treating a haematological cancer, comprising administering a DHODH inhibitor 2-(3,5-difluoro-3′-methoxybiphenyl-4-ylamino)nicotinic acid or a pharmaceutically acceptable salt thereof to a patient in need thereof, wherein the haematological cancer is selected from the group consisting of refractory cytopenia with multi-lineage dysplasia, multiple myeloma (MM) and chronic myeloid leukaemia (CML), wherein the DHODH inhibitor or pharmaceutically acceptable salt thereof is not administered for the treatment of a proliferative skin disorder.
2. A method of treatment according to claim 1 , wherein the haematological cancer is multiple myeloma (MM).
3. A method of treating chronic myeloid leukaemia (CML), comprising administering a DHODH inhibitor 2-(3,5-difluoro-3′-methoxybiphenyl-4-ylamino)nicotinic acid or a pharmaceutically acceptable salt thereof to a patient in need thereof.
4. A method of treatment according to claim 1 , wherein the DHODH inhibitor is employed in a combination therapy with a second therapy.
5. A method of treatment according to claim 4 , wherein the second therapy is an inhibitor of DNA repair.
6. A method of treatment according to claim 5 , wherein the inhibitor is selected from the group consisting of TRC 102, (2)-2-[(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1yl) methylene]-undecanoic acid [also known as E3330], NCS-666715, NSC-124854, 8-oxoguamine, tanespirmycin, alvespimycin, genetespib, retaspimycin, 6-amino-8-[(6-iodo-1,3-benzodioxol-5-yl)thio]-N-(1-methylethyl)-9H-purine-9-propanamine (PU-H71), 4[2-carbamoyl-5-[6,6-dimethyl-4-oxo-3-(trifluoromethyl)-5,7-dihydroindazol-1-yl]anilino ]cyclohexyl]2-aminoacetate (SNX-5422), luminespib (resorcyinylic), 2-(2-ethyl-3,5-dihydroxy -6-(3-methoxy-4-(2-morpholinoethoxy)benzoyl)phenyl)-N, N-bis(2-methoxyethyl)acetamide (KW-2478), AT13387, 5,6-bis((E)-benzylideneamino)-2-thioxo-2,3-dihydropyrimidin-4(1 H)-one (SCR7), olaparib, rucaparib, niraparib, iniparib, talazoparib, veliparib, CEP9722, E7016, BGB-290, AZD-2461, 3-aminobenzamide, 7-hydroxystaurosporine [UCN-01], trabectedin, MC113E, NER101 and combinations of two or more of the same.
7. A method according to claim 5 , wherein the second therapy is a topoisomerase inhibitor selected from the group consisting of irinotecan, topotecan, camptothecin lamellarin D, etoposide (VP-16), teniposide, doxorubicin, daunorubicin, mitoxantrone, arnsacrine, ellipticines, aurintricarboxylic acid, 3-hydroxy-2-[(1 R)-6-isopropenyl-3-methyl-cyclohex-2-en -1]-5-pentyl -1,4-benzoquinone (HU-331) and combinations thereof.
8. A method of treatment according to claim 1 , wherein the haematological cancer is refractory cytopenia with multi-lineage dysplasia.
9. A method of treatment according to claim 8 , wherein the refractory cytopenia with multi-lineage dysplasia is normal karyotype or karyotype 46, XY, 43.1 myeloid.