Use of Arginase in Combination with 5FU and Other Compounds for Treatment of Human Malignancies
The present invention provides a method for treating cancer in a human patient by reducing the physiological arginine levels to below 10 μM in combination with administering an anti-neoplastic compound. The present invention also provides a pharmaceutical composition comprising an arginine reducing compound, such as pegylated human arginase I, and an anti-neoplastic compound, such as 5 -fluorouracil, for the treatment of malignancies in a human patient.
1 . A method of treating cancer in a human patient, the method comprising reducing the physiological arginine levels in said patient to below 10 μM combined with administering an anti-neoplastic compound.
2 . The method according to claim 1 wherein said method of reducing the physiological arginine levels in said patient comprises embolization, dialysis, or administering an arginine reducing compound.
3 . The method according to claim 2 wherein said arginine reducing compound is an arginine degrading enzyme.
4 . The method according to claim 3 wherein said arginine degrading enzyme is arginase, arginine deiminase, arginine decarboxylase, modifications thereof or combinations thereof.
5 . The method according to claim 4 wherein said arginase is pegylated human arginase I.
6 . The method according to claim 1 wherein said anti-neoplastic compound is an alkylating agent, antimetabolite agent, antimitotic agent, DNA production inhibiting agent or DNA repair inhibiting agent.
7 . The method according to claim 1 wherein said anti-neoplastic compound is 5-fluorouracil.
8 . The method according to claim 1 wherein said arginine reducing step is achieved by administration of pegylated human arginase I and 5-fluorouracil to a patient.
9 . A kit for the treatment of human malignancies comprising at least one therapeutic dose of an arginine reducing compound and at least one therapeutic dose of an anti-neoplastic compound.
10 . The kit according to claim 9 wherein said arginine reducing compound is an arginine degrading enzyme.
11 . The kit according to claim 10 wherein said arginine degrading enzyme is arginase, arginine deiminase, arginine decarboxylase, modifications thereof or combinations thereof.
12 . The kit according to claim 11 wherein said arginase is human arginase I.
13 . The kit according to claim 11 wherein said arginase is pegylated human arginase.
14 . The kit according to claim 9 wherein said anti-neoplastic compound is an alkylating agent, antimetabolite agent, antibiotic agent, DNA production inhibiting agent or DNA repair inhibiting agent.
15 . The kit according to claim 9 wherein said anti-neoplastic compound is 5-fluorouracil.
16 . A pharmaceutical composition comprising an arginine reducing compound and an anti-neoplastic compound.
17 . The pharmaceutical composition according to claim 16 wherein said arginine reducing compound is an arginine degrading enzyme.
18 . The pharmaceutical composition according to claim 17 wherein said arginine degrading enzyme is arginase, arginine deiminase, arginine decarboxylase, or modifications and combinations thereof.
19 . The pharmaceutical composition according to claim 18 wherein said arginase is human arginase I.
20 . The pharmaceutical composition according to claim 18 wherein said arginase is pegylated human arginase.
21 . The pharmaceutical composition according to claim 16 wherein said anti-neoplastic compound is an alkylating agent, antimetabolite agent, antibiotic agent, DNA production inhibiting agent or DNA repair inhibiting agent.
22 . The pharmaceutical composition according to claim 16 wherein said anti-neoplastic compound is 5-fluorouracil.
23 . The pharmaceutical composition according to claim 16 wherein said pharmaceutical composition is a therapeutic dose for treating cancer
24 . Use of an arginine reducing compound in combination with an anti-neoplastic compound for the manufacture of a medicament for the treatment of cancer.
25 . The use according to claim 24 , wherein said arginine reducing compound is 5 an arginine degrading enzyme.
26 . The use according to claim 25 , wherein said arginine degrading enzyme is arginase, arginine deiminase, arginine decarboxylase, or modifications and combinations thereof wherein said arginine reducing compound is an arginine degrading enzyme.
27 . The use according to claim 26 , wherein said arginase is human arginase I.
28 . The use according to claim 26 , wherein said arginase is pegylated human arginase.
29 . The use according to claim 24 , wherein said anti-neoplastic compound is an 15 alkylating agent, antimetabolite agent, antibiotic agent, DNA production inhibiting agent or DNA repair inhibiting agent.’
30 . The use according to claim 24 , wherein said anti-neoplastic compound is 5-fluorouracil.