Therapeutic method for reducing angiogenesis

Abstract

A method of controlling or treating an angiogenic dependent condition in a mammal, preferably in a human by administering an anti angiogenic molecule such as an angiogenesis growth factor antagonist, and a chemotherapeutic agent in amounts and frequencies effective, in combination, to produce a regression or arrest of said condition while minimizing or preventing significant toxicity of the chemotherapeutic agent. Also a kit for controlling or treating an angiogenic dependent condition in a mammal, preferably in a human, comprising an anti-angiogenic molecule, such as an angiogenesis growth factor antagonist, and a chemotherapeutic agent in amounts effective, in combination, to produce a regression or arrest of said condition while minimizing or preventing significant toxicity of the chemotherapeutic agent.

1 . A method of treating a solid tumor in a human patient by inhibiting angiogenesis, comprising:
 administering to the human patient comprising a solid tumor selected from the group consisting of breast carcinoma, lung carcinoma, prostate carcinoma, colon carcinoma, ovarian carcinoma, neuroblastoma, central nervous system tumor, glioblastoma multiforme and melanoma:   (a) an antibody or binding fragment thereof that (i) specifically binds to a vascular endothelial growth factor (VEGF) and (ii) inhibits angiogenesis; and   (b) a chemotherapeutic agent having anti-angiogenic activity selected from the group consisting of vincristine, vinblastine, vinorelbine, vindesine, paclitaxel, docetaxel, 5 FU, cisplatin, carboplatin, irinotecan, topotecan and cyclophosphamide,   in amounts and frequencies effective, in combination, to inhibit formation of blood vessels supplying the solid tumor while minimizing or preventing toxicity of the chemotherapeutic agent, wherein the chemotherapeutic agent is administered at a dose intensity of less than about 10% of the dose intensity of the chemotherapeutic agent when used in a conventional chemotherapeutic regimen.   
     
     
         2 . The method of  claim 1 , wherein the vascular endothelial growth factor is VEGF-A. 
     
     
         3 . The method of  claim 1  or  2 , wherein synergistic tumor inhibition is obtained. 
     
     
         4 . The method of  claim 1  or  2 , wherein said administering is continued over a period of time from about 10 days to about 6 months. 
     
     
         5 . The method of  claim 4 , wherein said administering is continued for a period of about 6 months or longer than 6 months. 
     
     
         6 . The method of  claim 1 , wherein:
 the chemotherapeutic agent is selected from the group consisting of vincristine, vinblastine, vinorelbine, and vindesine;   the solid tumor is selected from the group consisting of neuroblastoma and neuroepithelioma.   
     
     
         7 . The method of  claim 6 , wherein the chemotherapeutic agent is vinblastine. 
     
     
         8 . The method of  claim 6 , wherein the vascular endothelial growth factor is VEGF-A. 
     
     
         9 . The method of  claim 6 , wherein said administering is continued for a period of about 6 months or longer than 6 months. 
     
     
         10 . The method of  claim 8 , wherein the vascular endothelial growth factor is VEGF-A. 
     
     
         11 . A method of treating a solid tumor in a human patient by inhibiting angiogenesis, comprising:
 administering to the human patient comprising a solid tumor selected from the group consisting of breast carcinoma, lung carcinoma, prostate carcinoma, colon carcinoma, ovarian carcinoma, neuroblastoma, central nervous system tumor, glioblastoma multiforme and melanoma:   (a) an antibody or binding fragment thereof that (i) specifically binds to a vascular endothelial growth factor (VEGF) and (ii) inhibits angiogenesis; and   (b) a chemotherapeutic agent having anti-angiogenic activity selected from the group consisting of vincristine, vinblastine, vinorelbine, vindesine, paclitaxel, docetaxel, 5 FU, cisplatin, carboplatin, irinotecan, topotecan and cyclophosphamide,   in amounts and frequencies effective, in combination, to inhibit formation of blood vessels supplying the solid tumor while minimizing or preventing toxicity of the chemotherapeutic agent, wherein the chemotherapeutic agent is administered weekly or more frequently than every 7 days at less than about 10% of the maximum tolerated dose.   
     
     
         12 . The method of  claim 11 , wherein the vascular endothelial growth factor is VEGF-A. 
     
     
         13 . The method of  claim 11  or  12 , wherein synergistic tumor inhibition is obtained. 
     
     
         14 . The method of  claim 11  or  12 , wherein said administering is continued over a period of time from about 10 days to about 6 months. 
     
     
         15 . The method of  claim 14 , wherein said administering is continued for a period of about 6 months or longer than 6 months. 
     
     
         16 . The method of  claim 11 , wherein:
 the chemotherapeutic agent is selected from the group consisting of vincristine, vinblastine, vinorelbine, and vindesine;   the solid tumor is selected from the group consisting of neuroblastoma and neuroepithelioma.   
     
     
         17 . The method of  claim 16 , wherein the chemotherapeutic agent is vinblastine. 
     
     
         18 . The method of  claim 16 , wherein the vascular endothelial growth factor is VEGF-A. 
     
     
         19 . The method of  claim 16 , wherein said administering is continued for a period of about 6 months or longer than 6 months. 
     
     
         20 . The method of  claim 18 , wherein the vascular endothelial growth factor is VEGF-A. 
     
     
         21 . The method of  claim 11 , wherein the chemotherapeutic agent is administered weekly or more frequently than every 7 days at less than about 5% of the maximum tolerated dose. 
     
     
         22 . The method of  claim 21 , wherein the vascular endothelial growth factor is VEGF-A. 
     
     
         23 . The method of  claim 21 , wherein the chemotherapeutic agent is administered weekly or more frequently than every 7 days at less than about 2% of the maximum tolerated dose. 
     
     
         24 . The method of  claim 23 , wherein the vascular endothelial growth factor is VEGF-A.