Method of Treating Cancer with DLL4 Antagonist and Chemotherapeutic Agent

Abstract

The invention provides methods for treating various types of cancer/tumor by administering the combination of Dll4 antagonists, in particular, Dll4 antibodies and fragments thereof that specifically bind human Dll4, and chemotherapeutic agents. Such combination therapies exhibit synergistic effects compared to the treatment with either agent alone. Thus, the methods of the invention are particularly beneficial for cancer patients who have low tolerance to the side effects caused by high dosages required for the treatment by either agent alone, by being able to reduce effective dosages. Pharmaceutical compositions and kits containing Dll4 antagonists and chemotherapeutic agents are also provided.

1 . A method of treating cancer or reducing or halting tumor growth in a subject, comprising administering to the subject an anti-DLL4 antibody and a chemotherapeutic agent such that cancer is treated, wherein the chemotherapeutic agent is selected from a platinum-based chemotherapeutic agent, an anti-mitotic agent of the taxoid or taxane family, or a pyrimidine analogue, and the cancer is selected from glioblastoma, breast cancer, bladder cancer, non-small-cell lung cancer, or colorectal cancer, and wherein the combination produces a synergistic therapeutic effect. 
     
     
         2 - 8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein the anti-mitotic agent is docetaxel or paclitaxel, or a pharmaceutically acceptable analogue or salt thereof. 
     
     
         10 . The method of  claim 1 , wherein the platinum-based chemotherapeutic agent is cisplatin, carboplatin, iproplatin, or oxaliplatin, or a pharmaceutically acceptable salt thereof. 
     
     
         11 . (canceled) 
     
     
         12 . The method of  claim 1 , wherein the pyrimidine analogue is gemcitabine, 5-FU, or capecitabine, or a pharmaceutically acceptable salt thereof. 
     
     
         13 - 16 . (canceled) 
     
     
         17 . The method of  claim 1 , wherein the antibody and the chemotherapeutic agent are administered concurrently. 
     
     
         18 . The method of  claim 1 , wherein the antibody and the chemotherapeutic agent are administered sequentially. 
     
     
         19 . The method of  claim 1 , wherein the subject is a human subject. 
     
     
         20 - 29 . (canceled) 
     
     
         30 . The method of  claim 9 , wherein the anti-mitotic agent is docetaxel. 
     
     
         31 . The method of  claim 10 , wherein the platinum-based chemotherapeutic agent is cisplatin. 
     
     
         32 . The method of  claim 12 , wherein the pyrimidine analogue is 5-FU. 
     
     
         33 . The method of  claim 1 , wherein the chemotherapeutic agent is cisplatin and the cancer is bladder cancer. 
     
     
         34 . The method of  claim 1 , wherein the chemotherapeutic agent is cisplatin and the cancer is non-small-cell lung cancer. 
     
     
         35 . The method of  claim 1 , wherein the chemotherapeutic agent is docetaxel and the cancer is glioblastoma. 
     
     
         36 . The method of  claim 1 , wherein the chemotherapeutic agent is docetaxel and the cancer is breast cancer. 
     
     
         37 . The method of  claim 1 , wherein the chemotherapeutic agent is 5-FU and the cancer is colorectal cancer.