Antineoplastic combinations with mTOR inhibitor,herceptin, and/or hki-272

Abstract

A combination of temsirolimus and herceptin in the treatment of cancer is provided. A combination of temsirolimus and HKI-272 is provided. A combination of herceptin and HKI-272 is also provided. Regimens and kits for treatment of metastatic breast cancer, containing herceptin, temsirolimus and/or HKI-272, optionally in combination with other anti-neoplastic agents, or immune modulators are described.

1 . A method of treating a neoplasm associated with overexpression or amplification of HER2 in a mammal in need thereof, which comprises providing to said mammal an effective amount of a combination of active components comprising a herceptin and an mTOR inhibitor and/or HKI-272.  
     
     
         2 . The method according to  claim 1 , wherein the combination comprises HKI-272.  
     
     
         3 . The method according to  claim 1  or  2 , wherein one or more of the active components is provided in subtherapeutically effective amounts.  
     
     
         4 . A method of treating a neoplasm associated with overexpression or amplification of HER2 in a mammal in need thereof, which comprises providing to said mammal an effective amount of a combination comprising a rapamycin and an HKI-272.  
     
     
         5 . The method according to any one of  claims 1  to  4 , wherein the neoplasm is selected from the group consisting of lung cancers, including bronchioalveolar carcinoma and non small cell lung cancer, breast cancers, myeloma, prostate cancers, head and neck cancer, or transitional cell carcinoma; small cell and large cell neuroendocrine carcinoma of the uterine cervix.  
     
     
         6 . The method according to any one of  claims 1  to  5 , wherein said combination further comprises another active component selected from the group consisting of one or more antineoplastic alkylating agent, one or more antimetabolite antineoplastic agents, one or more biochemical immune modulators, imatinib, one or more EGFR inhibitors, a multi-kinase inhibitor that targets serine/threonine and receptor tyrosine kinases in both the tumor cell and tumor vasculature or an interferon.  
     
     
         7 . The method according to  claim 6 , wherein said antineoplastic agents are selected from the group consisting of meclorethamine, cyclophosphamide, ifosfamide, melphalan, chlorambucil, thiotepa, mitomycin, busulfan, lomustine, carmustine, procarbazine, temozolomide, oxaliplatin, cisplatin, and carboplatin.  
     
     
         8 . The method according to  claim 7 , wherein the antimetabolite antineoplastic agent is selected from the group consisting of: 5-fluorouracil; floxuradine; thioguanine; cytarabine; fludarabine; 6-mercaptopurine; methotrexate; gemcitabine; capecitabine; taxanes; pentostatin; trimetrexatel; and cladribine.  
     
     
         9 . The method according to  claim 7 , wherein the biochemical modulating agent is selected from the group consisting of leucovorin and levofolinate.  
     
     
         10 . The method according to  claim 9 , wherein the combination further comprises a taxane.  
     
     
         11 . The method according to any one of  claims 1  to  10 , wherein the rapamycin is rapamycin.  
     
     
         12 . The method according to any one of  claims 1  to  10 , wherein the rapamycin is 42-O-(2-hydroxy)ethyl rapamycin.  
     
     
         13 . The method according to any one of  claims 1  to  12 , wherein the neoplasm is metastatic breast cancer.  
     
     
         14 . A regimen for treatment of breast cancer associated with overexpression or amplification of HER2, said method comprising: 
 delivering a dosage amount amount of a herceptin; and    delivering a dose of at least one additional compound selected from the group consisting of an mTOR inhibitor and a HKI-272.    
     
     
         15 . The regimen according to  claim 14 , wherein the rapamycin mTOR inhibitor and/or the herceptin is delivered intravenously.  
     
     
         16 . The regimen according to  claim 14 , wherein the rapamycin and/or the herceptin is delivered weekly.  
     
     
         17 . The regimen according to  claim 14 , wherein the rapamycin and/or the herceptin is delivered orally.  
     
     
         18 . The regimen according to  claim 14 , wherein the herceptin is delivered for at least two weeks following at least one week off.  
     
     
         19 . The regimen according to  claim 14 , wherein the herceptin is delivered for a period of four weeks followed by two weeks off.  
     
     
         20 . The regimen according to  claim 14 , wherein the herceptin is delivered once every three to four weeks.  
     
     
         21 . The regimen according to  claim 14 , wherein the rapamycin is selected from the group consisting of rapamycin and temsirolimus.  
     
     
         22 . The regimen according to  claim 14 , wherein the HKI-272 is delivered orally.  
     
     
         23 . A product containing temsirolimus and a herceptin as a combined preparation for simultaneous, separate or sequential use in treating a neoplasm in a mammal.  
     
     
         24 . A product containing a rapamycin and an HKI-272 as a combined preparation for simultaneous, separate or sequential use in treating a neoplasm in a mammal.  
     
     
         25 . A product containing a herceptin and an HKI-272 as a combined preparation for simultaneous, separate or sequential use in treating a neoplasm in a mammal.  
     
     
         26 . A pharmaceutical pack containing a course of an anti-neoplastic treatment for one individual mammal, wherein the pack contains (a) at least one unit of temsirolimus and (b) at least one unit of herceptin in unit dosage form.  
     
     
         27 . A pharmaceutical pack containing a course of an anti-neoplastic treatment for one individual mammal, wherein the pack contains (a) at least one unit of a rapamycin and (b) at least one unit of HKI-272 in unit dosage form.  
     
     
         28 . A pharmaceutical pack containing a course of an anti-neoplastic treatment for one individual mammal, wherein the pack contains (a) at least one unit of herceptin and (b) at least one unit of HKI-272 in unit dosage form.  
     
     
         29 . A pharmaceutical composition useful in treating a neoplasm in a mammal, the composition comprising (a) at least one unit of temsirolimus and (b) at least one unit of a herceptin in unit dosage form, and at least one pharmaceutically acceptable carrier.  
     
     
         30 . A pharmaceutical composition useful in treating a neoplasm in a mammal, the composition comprising (a) at least one unit of a rapamycin and (b) at least one unit of an HKI-272 in unit dosage form, and at least one pharmaceutically acceptable carrier.  
     
     
         31 . A pharmaceutical composition useful in treating a neoplasin in a mammal, the composition comprising (a) at least one unit of a herceptin and (b) at least one unit of an HKI-272 in unit dosage form, and at least one pharmaceutically acceptable carrier.