A pharmaceutical composition comprising a hdac inhibitor and a steroid and the use thereof

Abstract

The invention relates to a pharmaceutical composition comprising a HDAC inhibitor, a pharmaceutically acceptable acid or a salt thereof or a mixture thereof and a steroid or a pharmaceutically acceptable salt thereof as well use of said pharmaceutical composition for the treatment of cancer as a pretreatment prior to other treatments. Said HDAC inhibitor or steroid may alternatively be administrated separately prior to additional treatments.

1 . A pharmaceutical composition comprising
 a. a HDAC inhibitor, a pharmaceutically acceptable acid or a salt thereof or a mixture thereof and   b. a steroid or a pharmaceutically acceptable salt thereof.   
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein the HDAC inhibitor is a hydroxamic/carbamic acid, a cyclic peptide, an aliphatic acid or a benzamide compound. 
     
     
         3 . The composition according to  claim 2 , wherein the HDAC inhibitor is selected from the group consisting of vorinostat, romidepsin, valproic acid, aspanobinostat, panobinostat, belinostat, entinostat and resminostat. 
     
     
         4 . The composition according to  claim 3 , wherein the HDAC inhibitor is selected from the group consisting of valproic acid or valproate semisodium, sodium valproate or magnesium valproate. 
     
     
         5 . The composition according to  claim 1 , wherein the steroid is selected from the group consisting of prednisone, prednisolone, dexamethasone or betamethasone. 
     
     
         6 . The composition according to  claim 5 , wherein the steroid is prednisone. 
     
     
         7 . The composition according to  claim 1 , wherein the HDAC inhibitor is valproic acid and the steroid is prednisone. 
     
     
         8 . The composition according to  claim 1 , further comprising a pharmaceutically acceptable additive, diluent, carrier, excipient or buffer. 
     
     
         9 . The composition according to  claim 1 , which is selected from the group consisting of granulates, powders, tablets, coated tablets, microcapsules, microgranulates or effervescent forms. 
     
     
         10 . The composition according to  claim 1 , wherein said effervescent form is selected from the group consisting of tablets or powders. 
     
     
         11 . A device selected from the group consisting of a vial, ampule, pouch or infusion bag comprising the composition according to  claim 1  or one device comprising a HDAC inhibitor, a pharmaceutically acceptable acid or a salt thereof or a mixture thereof and one device comprising a steroid or a pharmaceutically acceptable salt thereof. 
     
     
         12 . A HDAC inhibitor, a pharmaceutically acceptable acid or a salt thereof or a mixture thereof and a steroid or a pharmaceutically acceptable salt thereof for the pretreatment of cancer. 
     
     
         13 . A HDAC inhibitor, a pharmaceutically acceptable acid or a salt thereof or a mixture thereof and a steroid or a pharmaceutically acceptable salt thereof for the pretreatment of sarcoma, malignant melanoma, skin cancer, estrogen receptor-dependent and independent breast cancer, ovarian cancer, prostate cancer, renal cancer, colon and colorectal cancer, pancreatic cancer, head and neck cancer, small cell and non-small cell lung carcinoma, and cancer of blood cells. 
     
     
         14 . A HDAC inhibitor, a pharmaceutically acceptable acid or a salt thereof or a mixture thereof and a steroid or a pharmaceutically acceptable salt thereof for the pretreatment of a diseases selected from the group consisting of diffuse large B cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukaemia, T cell lymphoma, myeloma and Hodgkin lymphoma. 
     
     
         15 . A kit, comprising the pharmaceutical composition according to  claim 1  provided in a suitable container and/or with suitable packaging and instruction for use. 
     
     
         16 . A kit comprising a HDAC inhibitor or a pharmaceutically acceptable acid or a salt thereof or mixture thereof and a steroid or a pharmaceutically acceptable salt thereof provided in a suitable container and/or with suitable packaging and instruction for use, for example how to administer the compounds. 
     
     
         17 . The kit according to  claim 16 , wherein the two active compounds are kept in separate containers and/or in different packages. 
     
     
         18 . The kit according to  claim 15 , wherein said kit further comprises an antibody, monoclonal antibody or functional fragments thereof which binds to CD20. 
     
     
         19 . The kit according to  claim 15 , wherein said container is a vial, ampule, pouch or infusion bag. 
     
     
         20 . A method of pretreating a human being suffering from cancer by administrating a pharmaceutical compositing according to  claim 1 . 
     
     
         21 . A method of pretreating a human being suffering from cancer by administrating a HDAC inhibitor, a pharmaceutically acceptable acid or a salt thereof or a mixture thereof and a steroid or a pharmaceutically acceptable salt thereof for the pretreatment of cancer, simultaneously or sequentially. 
     
     
         22 . The method according to  claim 20 , wherein the pretreatment is followed by a chemotherapy and/or immunotherapy. 
     
     
         23 . The method according to  claim 20  for the treatment of sarcoma, malignant melanoma, skin cancer, estrogen receptor-dependent and independent breast cancer, ovarian cancer, prostate cancer, renal cancer, colon and colorectal cancer, pancreatic cancer, head and neck cancer, small cell and non-small cell lung carcinoma, and cancer of blood cells. 
     
     
         24 . The method according to  claims 23  for the treatment of a diseases selected from the group consisting of diffuse large B cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukaemia, T-cell lymphoma, myeloma and Hodgkin lymphoma. 
     
     
         25 . A method of evaluating a substance effect on the CHOP-sensitivity of cell lines, comprising the steps of
 a. Providing a cell line selected from the group consisting of WSU-NHL, Karpas-422, ULA, SU-DHL-5 and SU_DHL-8   b. Adding a combination of cyclophosphamide, doxorubicin, vincristin and prednisolone   c. Adding a substance to be evaluated to each cell line   d. And evaluating the viability of the cells.