Combinations for the treatment of diseases involving cell proliferation, migration or apoptosis of myeloma cells, or angiogenesis

Abstract

The present invention relates to a pharmaceutical combination for the treatment of diseases which involves cell proliferation, migration or apoptosis of myeloma cells, or angiogenesis. The invention also relates to a method for the treatment of said diseases, comprising co-administration of effective amounts of specific active compounds and/or co-treatment with radiation therapy, in a ratio which provides an additive and synergistic effect, and to the combined use of these specific compounds and/or radiotherapy for the manufacture of corresponding pharmaceutical combination preparations.

1 . A pharmaceutical combination preparation kit, comprising therapeutically effective amounts of:
 (i) (Z)-3-(1-(4-(N-((4-methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone, or a pharmaceutically acceptable salt thereof; and   (ii) 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-buten-1-yl]amino}-7-((S)-tetrahydrofuran-3-yloxy)-quinazoline or a pharmaceutical acceptable salt, the tautomers or the stereoisomers thereof;   and optionally adapted for a co-treatment with radiotherapy or radio-immunotherapy, characterised in that (i) is comprised within a first compartment and (ii) is comprised within a second compartment, such that the administration to a patient in need thereof can be simultaneous, separate or sequential.   
     
     
         2 . The pharmaceutical combination preparation kit in accordance with  claim 1 , wherein (i) is the monoethanesulfonate salt of 3-Z-[1-(4-(N-((4-methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone. 
     
     
         3 . The pharmaceutical combination preparation kit in accordance with  claim 1 , wherein (ii) is the quinazoline derivative 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-buten-1-yl]amino}-7-((S)-tetrahydrofuran-3-yloxy)-quinazoline or a pharmaceutically acceptable salt thereof. 
     
     
         4 . The pharmaceutical combination preparation kit in accordance with  claim 3 , wherein (ii) is the di-maleic acid salt of the compound 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-buten-1-yl]amino}-7-((S)-tetrahydrofuran-3-yloxy)-quinazoline. 
     
     
         5 . The pharmaceutical combination preparation kit in accordance with any of  claims 1  to  4 , wherein the formulation of the (i) is for oral administration.