ARYL UREA COMPOUNDS IN COMBINATION WITH OTHER CYTOSTATIC OR CYTOTOXIC AGENTS FOR TREATING HUMAN CANCERS
This invention relates to aryl urea compounds in combination with cytotoxic or cytostatic agents for use in treating raf kinase mediated diseases such as cancer.
1 .- 9 . (canceled)
10 . A drug combination for treating a cancer in a patient comprising a tosylate salt of N-(4-chloro-3-(trifluoromethypphenyl-N′-(4-(2-(N-methylcarbamoyl)-4-pyridoxy)phenyl)urea and a cytotoxic or a cytostatic chemotherapeutic agent which is (a) a DNA topoisomerase I or H inhibitor, (b) a DNA intercalator, (c) an alkylating agent, (d) a microtubule disruptor, (e) a hormone or a growth factor receptor agonist or antagonist, (f) a kinase inhibitor or (g) an antimetabolite.
11 . The drug combination of claim 10 , comprising a tosylate salt of N-(4-chloro-3-(trifluoromethypphenyl-N′-(4-(2-(N-methylcarbamoyl)-4-pyridoxy)phenyl)urea and (g) an antimetabolite.
12 . The drug combination of claim 10 , wherein the antimetabolite is 5-fluorouracil.
13 . The drug combination of claim 10 , which comprises about 0.1 to about 300 mg/kg of total body weight of the tosylate salt of N-(4-chloro-3-(trifluoromethypphenyl-N′-(4-(2-(N-methylcarbamoyl)-4-pyridoxy)phenyl)urea and from about 0.1 to about 300 mg/kg of total body weight of the cytotoxic or the cytostatic chemotherapeutic agent.
14 . A method for treating a cancer in a patient, comprising administering to said patient a therapeutically effective amount of a tosylate salt of N-(4-chloro-3-(trifluoromethypphenyl-N′-(4-(2-(N-methylcarbamoyl)-4-pyridoxy)phenyl)urea and a therapeutically effective amount of a cytotoxic or cytostatic chemotherapeutic agent which is (a) a DNA topoisomerase I or H inhibitor, (b) a DNA intercalator, (c) an alkylating agent, (d) a microtubule disruptor, (e) a hormone or a growth factor receptor agonist or antagonist, (f) a kinase inhibitor or (g) an antimetabolite.
15 . The method of claim 14 , wherein said tosylate salt of N-(4-chloro-3-(trifluoromethypphenyl-N′-(4-(2-(N-methylcarbamoyl)-4-pyridoxy)phenyl)urea is administered to a patient at an oral, intramuscular, intravenous, subcutaneous, or parenteral dosage which can range from about 0.1 to about 300 mg/kg of total body weight and said cytotoxic or a cytostatic chemotherapeutic agent is administered to a patient at an oral, intramuscular, intravenous, subcutaneous, or parenteral dosage which can range from about 0.1 to about 300 mg/kg of total body weight.
16 . A method for treating a cancer which is colon, gastric, lung, pancreatic, ovarian, prostate, leukemia, melanoma, hepatocellular, renal, head and neck, glioma, or mammary cancer in a patient comprising administering to said patient a therapeutically effective amount of a composition comprising a tosylate salt of N-(4-chloro-3-(trifluoromethyl)phenyl-N′-(4-(2-(N-methylcarbamoyl)-4-pyridoxy)phenyl)urea and a therapeutically effective amount of 5-flurouracil.
17 . The method of claim 16 , wherein the cancer is colon cancer or hepatocellular cancer.
18 . The method according to claim 16 , wherein hepatocellular cancer is treated by the administration of a therapeutically effective amount of a tosylate salt of N-(4-chloro-3-(trifluoromethyl)phenyl-N′-(4-(2-(N-methylcarbamoyl)-4-pyridoxy)phenyl)urea and a therapeutically effective amount of 5-flurouracil.