Combination therapy for neoplasia treatment

Abstract

The present invention relates to an insulin-like growth factor (IGF) receptor antagonist for use in the treatment of prostate neoplasia, including benign prostatic hyperplasia (BPH), prostate cancer, and particularly CRPC, wherein the antagonist is used in combination with an androgen receptor antagonist. An embodiment of the invention is where the androgen receptor antagonist is enzalutamide.

1 . An insulin-like growth factor (IGF) receptor antagonist for use in the treatment of prostate neoplasia in combination with an androgen receptor antagonist. 
     
     
         2 . The IGF receptor antagonist of  claim 1  wherein the prostate neoplasia, is benign prostatic hyperplasia (BPH) or prostate cancer. 
     
     
         3 . The IGF receptor antagonist of  claim 1  wherein the prostate cancer, is castration resistent prostate cancer. 
     
     
         4 . The IGF receptor antagonist of  claim 1  which is an antibody against IGF-1, and antibody against IGF-2, an antibody against both IGF-1 and IGF-2, an antibody against IGF-1 receptor (IGF-1R), or an inhibitor of IGF-1R tyrosine kinase activity. 
     
     
         5 . The IGF receptor antagonist of  claim 1  which is an antibody having heavy chain complementary determining regions of SEQ ID NO: 1 (HCDR1), SEQ ID NO: 2 (HCDR2), and SEQ ID NO: 3 (HCDR3) and light chain determining regions of SEQ ID NO: 4 (LCDR1), SEQ ID NO: 5 (LCDR2), and SEQ ID NO: 6 (LCDR3), or an antibody having heavy chain complementary determining regions of SEQ ID NO: 11 (HCDR1), SEQ ID NO: 12 (HCDR2), and SEQ ID NO: 13 (HCDR3) and light chain determining regions of SEQ ID NO: 14 (LCDR1), SEQ ID NO: 15 (LCDR2), and SEQ ID NO: 16 (LCDR3), or an antibody having heavy chain complementary determining regions of SEQ ID NO: 21 (HCDR1), SEQ ID NO: 22 (HCDR2), and SEQ ID NO: 23 (HCDR3) and light chain determining regions of SEQ ID NO: 24 (LCDR1), SEQ ID NO: (LCDR2), and SEQ ID NO: 26 (LCDR3), or an antibody having heavy chain complementary determining regions of SEQ ID NO: 31 (HCDR1), SEQ ID NO: 32 (HCDR2), and SEQ ID NO: 33 (HCDR3) and light chain determining regions of SEQ ID NO: 34 (LCDR1), SEQ ID NO: 35 (LCDR2), and SEQ ID NO: 36 (LCDR3), or an antibody having a heavy chain variable region of SEQ ID NO: 7 and a light chain variable region of SEQ ID NO: 8, or an antibody having a heavy chain variable region of SEQ ID NO: 17 and a light chain variable region of SEQ ID NO: 18), or an antibody having a heavy chain variable region of SEQ ID NO: 27 and a light chain variable region of SEQ ID NO: 28), or an antibody having a heavy chain variable region of SEQ ID NO: 37 and a light chain variable region of SEQ ID NO: 38), or an antibody having a heavy chain variable region of SEQ ID NO: 41 and a light chain variable region of SEQ ID NO: 42), or an antibody having a heavy chain variable region of SEQ ID NO: 43 and a light chain variable region of SEQ ID NO: 44, or an antibody having a heavy chain of SEQ ID NO: 9, and a light chain of SEQ ID NO: 10, or an antibody having a heavy chain of SEQ ID NO: 19, and a light chain of SEQ ID NO: 20, or an antibody having a heavy chain of SEQ ID NO: 29, and a light chain of SEQ ID NO: 30, or an antibody having a heavy chain of SEQ ID NO: 39, and a light chain of SEQ ID NO: 40, or an antibody having a heavy chain of SEQ ID NO: 45, and a light chain of SEQ ID NO: 46. 
     
     
         6 . The IGF receptor antagonist of  claim 5  wherein the antibody has a heavy chain of SEQ ID NO: 39, and a light chain of SEQ ID NO: 40 
     
     
         7 . The IGF receptor antagonist of  claim 1 , wherein the androgen receptor antagonist is an anti-androgen, an androgen synthesis inhibitor, a 17 α-hydroxylase/C17,20 lyase (CYP17A1) inhibitor, a 5-alpha-reductase inhibitor, a corticosteroid, a luteinizing hormone-releasing hormone (LH-RH) agonist, or an estrogen agonist. 
     
     
         8 . The IGF receptor antagonist of  claim 7 , wherein the androgen receptor antagonist is flutamide, nilutamide, enzalutamide, bicalutamide, ketonazole, abiraterone, abiraterone acetate, orteronel, finasteride, dutasteride, bexlosteride, izonsteride, turosteride, episteride, dexamethasone, prednisone, leuprolide, goserelin, triptorelin, histrelin, or estrogen. 
     
     
         9 . An androgen receptor antagonist for use in the treatment of prostate neoplasia in combination with an IGF receptor antagonist. 
     
     
         10 . The androgen receptor antagonist of  claim 9  which is flutamide, nilutamide, enzalutamide, bicalutamide, ketonazole, abiraterone, abiraterone acetate, orteronel, finasteride, dutasteride, bexlosteride, izonsteride, turosteride, episteride, dexamethasone, prednisone, leuprolide, goserelin, triptorelin, histrelin, or estrogen. 
     
     
         11 . Method of treatment of prostate neoplasia comprising administering a therapeutically effective amount of an IGF receptor antagonist to a patient in need thereof, and additionally administering a therapeutically effective amount of an androgen receptor antagonist to the same patient within seven days before or after administration of the IGF receptor antagonist. 
     
     
         12 . Use of an IGF receptor antagonist for the manufacture of a medicament for the treatment of prostate neoplasia, wherein the IGF receptor antagonist is to be used in combination with an androgen receptor antagonist. 
     
     
         13 . Use of an androgen receptor antagonist for the manufacture of a medicament for the treatment of prostate neoplasia, wherein the androgen receptor antagonist is to be used in combination with an IGF receptor antagonist. 
     
     
         14 . Pharmaceutical composition, comprising an IGF receptor antagonist and an androgen receptor antagonist, together with a pharmaceutically acceptable carrier.