Pharmaceutical combinations comprising for the treatment of specific cancers

A method of treating or preventing non-small cell lung cancer, breast cancer, thyroid cancer, melanoma, pancreatic cancer, adenocarcinoma, hepatoma, or colon cancer,

• wherein for treating or preventing non-small cell lung cancer, the method comprises administering to an individual in need thereof a synergistic combination provided under I, II or III,
• wherein for treating or preventing breast cancer, the method comprises administering to an individual in need thereof a synergistic combination provided under IV, V, or VI,
• wherein for treating or preventing thyroid cancer, the method comprises administering to an individual in need thereof a synergistic combination provided under VII, VIII, IX or X,
• wherein for treating or preventing melanoma, the method comprises administering to an individual in need thereof a synergistic combination provided under XI or XII,
• wherein for treating or preventing pancreatic cancer, the method comprises administering to an individual in need thereof a synergistic combination provided under XIII,
• wherein for treating or preventing adenocarcinoma, the method comprises administering to an individual in need thereof a synergistic combination provided under XIV,
• wherein for treating or preventing hepatoma, the method comprises administering to an individual in need thereof a synergistic combination provided under XV,
• wherein for treating or preventing colon cancer, the method comprises administering to an individual in need thereof a synergistic combination provided under XVI,
• I:
• a. a therapeutically-effective amount of (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide, a salt thereof, or a polymorph thereof (see e.g., U.S. application Ser. No. 12/399,848);
• and
• b. a therapeutically-effective amount of 3-(6,7-bis(2-methoxyethoxy)quinazolin-4-ylamino)benzonitrile:
• II:
• a. a therapeutically-effective amount of (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide, a salt thereof, or a polymorph thereof (see e.g., U.S. application Ser. No. 12/399,848);
• and
• b. a therapeutically-effective amount of N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine:
• III:
• a. a therapeutically-effective amount of (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide, a salt thereof, or a polymorph thereof (see e.g., U.S. application Ser. No. 12/399,848);
• and
• b. a therapeutically-effective amount of 4-amino-1-[3,3-difluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-1H-pyrimidin-2-one:
• IV:
• a. a therapeutically-effective amount of (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide, a salt thereof, or a polymorph thereof (see e.g., U.S. application Ser. No. 12/399,848);
• and
• b. a therapeutically-effective amount of N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine:
• V:
• a. a therapeutically-effective amount of (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide, a salt thereof, or a polymorph thereof (see e.g., U.S. application Ser. No. 12/399,848);
• and
• b. a therapeutically-effective amount of 4-amino-1-[3,3-difluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-1H-pyrimidin-2-one:
• VI:
• a. a therapeutically-effective amount of (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide, a salt thereof, or a polymorph thereof (see e.g., U.S. application Ser. No. 12/399,848);
• and
• b. a therapeutically-effective amount of N-[3-chloro-4-[(3-fluorophenyl)methoxylphenyl]-6-[5-1(2-methylsulfonylethylamino)methyl]-2-furyl]quinazolin-4-amine:
• VII
• a. a therapeutically-effective amount of (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide, a salt thereof, or a polymorph thereof (see e.g., U.S. application Ser. No. 12/399,848);
• and
• b. a therapeutically-effective amount of N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine:
• VIII:
• a. a therapeutically-effective amount of (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide, a salt thereof, or a polymorph thereof (see e.g., U.S. application Ser. No. 12/399,848);
• and
• b. a therapeutically-effective amount of 4-amino-1-[3,3-difluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-1H-pyrimidin-2-one:
• IX:
• a. a therapeutically-effective amount of (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide, a salt thereof, or a polymorph thereof (see e.g., U.S. application Ser. No. 12/399,848);
• and
• b. a therapeutically-effective amount of N-hydroxy-N′-phenyl-octanediamide:
• X:
• a. a therapeutically-effective amount of (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide, a salt thereof, or a polymorph thereof (see e.g., U.S. application Ser. No. 12/399,848);
• and
• b. a therapeutically-effective amount of N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]-2-furyl]quinazolin-4-amine:
• XI:
• a. a therapeutically-effective amount of (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide, a salt thereof, or a polymorph thereof (see e.g., U.S. application Ser. No. 12/399,848);
• and
• b. a therapeutically-effective amount of 4-amino-1-[3,3-difluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-1H-pyrimidin-2-one:
• XII:
• a. a therapeutically-effective amount of (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide, a salt thereof, or a polymorph thereof (see e.g., U.S. application Ser. No. 12/399,848);
• and
• b. a therapeutically-effective amount of 4-methyl-5-oxo-2,3,4,6,8-pentazabicyclo[4.3.0]nona-2,7,9-triene-9-carboxamide:
• XIII:
• a. a therapeutically-effective amount of (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide, a salt thereof, or a polymorph thereof (see e.g., U.S. application Ser. No. 12/399,848);
• and
• b. a therapeutically-effective amount of 4-amino-1-[3,3-difluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-1H-pyrimidin-2-one:
• XIV:
• a. a therapeutically-effective amount of (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide, a salt thereof, or a polymorph thereof (see e.g., U.S. application Ser. No. 12/399,848);
• and
• b. a therapeutically-effective amount of (1R,2R,4S)-4-{(2R)-2-R3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-1,5,11,28,29-pentaoxo-1,4,5,6,9,10,11,12,13,14,21,22,23,24,25,26,27,28,29,31,32,33,34,34a-tetracosahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontin-3-yl]propyl}-2-methoxycyclohexyl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate:
• XV:
• a. a therapeutically-effective amount of (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide, a salt thereof, or a polymorph thereof (see e.g., U.S. application Ser. No. 12/399,848);
• and
• b. a therapeutically-effective amount of (1R,2R,4S)-4-{(2R)-2-[(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-1,5,11,28,29-pentaoxo-1,4,5,6,9,10,11,12,13,14,21,22,23,24,25,26,27,28,29,31,32,33,34,34a-tetracosahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontin-3-yl]propyl}-2-methoxycyclohexyl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate:
• XVI:
• a. a therapeutically-effective amount of (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide, a salt thereof, or a polymorph thereof (see e.g., U.S. application Ser. No. 12/399,848);
• and
• b. a therapeutically-effective amount of dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl]propan-2-yl]-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone:

A composition A, B, C, D, E, F, G or H, comprising:

• A:
• a. a therapeutically-effective amount of (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide, a salt thereof, or a polymorph thereof (see e.g., U.S. application Ser. No. 12/399,848);
• and
• b. a therapeutically-effective amount of 3-(6,7-bis(2-methoxyethoxy)quinazolin-4-ylamino)benzonitrile:
• B:
• a. (a therapeutically-effective amount of (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide, a salt thereof, or a polymorph thereof (see e.g., U.S. application Ser. No. 12/399,848);
• and
• b. a therapeutically-effective amount of N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine:
• C:
• a. a therapeutically-effective amount of (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide, a salt thereof, or a polymorph thereof (see e.g., U.S. application Ser. No. 12/399,848);
• and
• b. a therapeutically-effective amount of 4-amino-1-[3,3-difluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-1H-pyrimidin-2-one:
• D:
• a. a therapeutically-effective amount of (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide, a salt thereof, or a polymorph thereof (see e.g., U.S. application Ser. No. 12/399,848);
• and
• b. a therapeutically-effective amount of N-hydroxy-N′-phenyl-octanediamide:
• E:
• a. a therapeutically-effective amount of (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide, a salt thereof, or a polymorph thereof (see e.g., U.S. application Ser. No. 12/399,848);
• and
• b:
• a therapeutically-effective amount of 4-methyl-5-oxo-2,3,4,6,8-pentazabicyclo[4.3.0]nona-2,7,9-triene-9-carboxamide:
• F:
• a:
• a therapeutically-effective amount of (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide, a salt thereof, or a polymorph thereof (see e.g., U.S. application Ser. No. 12/399,848);
• and
• b:
• a therapeutically-effective amount of N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]-2-furyl]quinazolin-4-amine:
• G:
• a:
• a therapeutically-effective amount of (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide, a salt thereof, or a polymorph thereof (see e.g., U.S. application Ser. No. 12/399,848);
• and
• b. a therapeutically-effective amount of (1R,2R,4S)-4-{(2R)-2-[(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-1,5,11,28,29-pentaoxo-1,4,5,6,9,10,11,12,13,14,21,22,23,24,25,26,27,28,29,31,32,33,34,34a-tetracosahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontin-3-yl]propyl}-2-methoxycyclohexyl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate:
• H:
• a:
• a therapeutically-effective amount of (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide, a salt thereof, or a polymorph thereof (see e.g., U.S. application Ser. No. 12/399,848);
• and
• b:
• a therapeutically-effective amount of Dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl]propan-2-yl]-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone: