Combinatorial therapies for the treatment of neoplasias using the opioid growth factor receptor

Abstract

The present invention relates to pharmaceutical compositions for treating neoplasias in an animal or human comprised of a carrier and therapeutically effective amounts of at least one chemotherapeutic agent along with the biotherapeutic endogenous pentapeptide Met-enkephalin, referred to as opioid growth factor. Also provided are methods of treating neoplasias in an animal or human in need of such treatment, comprising the administration to the animal or human therapeutically effective amounts of a pharmaceutical composition comprised of a carrier and therapeutically effective amounts of at least one neoplasia-treating agent, such as a chemotherapeutic agent or radiation, along with opioid growth factor.

The invention claimed is: 
     
         1 . A pharmaceutical composition for treating neoplasias in an animal or human which are characterized by an opioid growth factor receptor, comprising: therapeutically effective amounts of at least one chemotherapeutic, biotherapeutic, and/or radionuclide agent with opioid growth factor; and a carrier. 
     
     
         2 . The pharmaceutical composition of  claim 1  wherein said agent is a therapeutic agent. 
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the neoplasias includes not limited to pancreatic cancer, squamous cell cancer of the head and neck, breast cancer, colorectal cancer, renal cancer, brain cancer, prostate cancer, bladder cancer, bone or joint cancer, uterine cancer, cervical cancer, endometrial cancer, multiple myeloma, Hodgkin's disease, non-Hodgkin's lymphoma, melanoma, leukemias, lung cancer, ovarian cancer, gastrointestinal cancer, Kaposi's sarcoma, liver cancer, pharyngeal cancer and laryngeal cancer. 
     
     
         4 . The pharmaceutical composition of  claim 3 , wherein the chemotherapeutic agent is selected from but not limited to the group comprising: busulfan, cisplatin, carboplatin, chlorambucil, cyclophosphamide, ifosfamide, dacarbazine (DTIC), mechlorethamine (nitrogen mustard), melphalan carmustine (BCNU) lomustine (CCNU), 5-FU, capecitabine, methotrexate, gemcitabine, cytarabine (ara-C), fludarabine dactinomycin, daunorubicin, doxorubicin (Adriamycin), idarubicin, mitoxantrone, paclitaxel, docetaxel, etoposide (VP-16), vinblastine, vincristine, vinorelbine prednisone, dexamethasone, tamoxifen, fulvestrant, anastrozole, letrozole, megestrol acetate, bicalutamide, flutamide, leuprolide, goserelin, L-asparaginase, and tretinoin. gemcitabine, paclitaxel, carboplatin, and 5-FU. 
     
     
         5 . The pharmaceutical composition of  claim 4 , wherein the therapeutic effective amount of OGF is about 100 to 400 μg/kg body weight when administered intravenously. 
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein the therapeutic effective amount of the chemotherapeutic agent ranges from about 100 to 1000 mg/m2 when administered intravenously. 
     
     
         7 . A method for treating neoplasias characterized by an opioid growth factor receptor in an animal or human in need of such treatment, comprising: administering to said animal or human therapeutically effective amounts of each of at least one neoplasia-treating agent and opioid growth factor. 
     
     
         8 . The method of  claim 7  wherein said neoplasia treating agent is radiation. 
     
     
         9 . The method of  claim 7  wherein said neoplasia treating agent is a biotherapy agent. 
     
     
         10 . The method of  claim 7  wherein said neoplasia treating agent is a chemotherapy agent. 
     
     
         11 . The method of  claim 7  wherein said neoplasia treating agent is a radionuclide. 
     
     
         12 . The method of  claim 7 , wherein the opioid growth factor specifically binds to an opioid growth factor receptor. 
     
     
         13 . The method of  claim 7 , wherein the neoplasias includes but is not limited to pancreatic cancer, squamous cell cancer of the head and neck, breast cancer, colorectal cancer, renal cancer, brain cancer, prostate cancer, bladder cancer, bone or joint cancer, uterine cancer, cervical cancer, endometrial cancer, multiple myeloma, Hodgkin's disease, non-Hodgkin's lymphoma, melanoma, leukemias, lung cancer, ovarian cancer, gastrointestinal cancer, Kaposi's sarcoma, liver cancer, pharyngeal cancer and laryngeal cancer. 
     
     
         14 . The method of  claim 7 , wherein the neoplasia-treating agent is a chemotherapeutic agent including but is not limited to gemcitabine, paclitaxel, carboplatin, and 5-fluorouracil. 
     
     
         15 . The method of  claim 7 , wherein the therapeutic effective amount of opioid growth factor administered is about 100 to 400 μg/k:g body weight per day when administered intravenously. 
     
     
         16 . The method of  claim 7 , further comprising: administering a chemotherapeutic agent sequentially or simultaneously with opioid growth factor in therapeutically effective amounts ranging from about 100 to 1000 mg/m2 intravenously (OGF continuous treatment over a period of between about 10 to 60 minutes at least once a week for about three to ten weeks followed by a one to three week rest period; administering the chemotherapeutic agent at least once weekly for about one to five weeks after the one to three week rest period; and repeating the administration of the chemotherapeutic agent every two to eight weeks. 
     
     
         17 . The method according to  claim 12 , wherein opioid growth factor is given continuously throughout the treatment period, when the therapeutic agent(s) is/are administered intermittently. 
     
     
         18 . The method of  claim 10 , wherein the route of administration of the at least one chemotherapeutic agent and opioid growth factor is selected from the group consisting of parenterally, including intravenously, intramuscularly or intraperitoneally; subcutaneously, implanted osmotic pump and transdermal patch. 
     
     
         19 . A method of decreasing the toxicity of paclitaxel comprising: administering with said paclitaxel an effective amount of opioid growth factor. 
     
     
         20 . A method of increasing the anti-neoplastic effects of a chemotherapeutic agent selected from the group including consisting of: gemcitabine, paclitaxel, carboplatin, and 5-FU comprising: introducing to said neoplastic cells, in combination with said chemotherapeutic agent, a therapeutically effective amount of OGF, wherein the neoplastic cell killing observed with said combination is greater than the neoplastic cell killing of the chemotherapeutic agent alone. 
     
     
         21 . A method for killing neoplastic cells characterized by an opioid growth factor receptor in an animal or human in need of such treatment, comprising: administering to said animal or human a therapeutically effective amounts of a chemotherapeutic agent selected from and not limited to the group comprising: gemcitabine, paclitaxel, carboplatin, and 5-FU; and opioid growth factor. 
     
     
         22 . A method for killing neoplastic pancreatic cells characterized by an opioid growth factor receptor in an animal or human in need of such treatment, comprising: administering to said animal or human a therapeutically effective amounts of a chemotherapeutic agent selected from but not limited to the group compromising: 30 gemcitabine, and 5-FU; and opioid growth factor. 
     
     
         23 . A method for killing neoplastic squamous cells characterized by an opioid growth factor receptor in an animal or human in need of such treatment, comprising: administering to said animal or human a therapeutically effective amount of a chemotherapeutic agent selected from the group consisting of paclitaxel, and carboplatin; and opioid growth factor. 
     
     
         24 . A pharmaceutical composition for treating neoplasias in an animal or human which are characterized by an opioid growth factor receptor, comprising: therapeutically effective amounts of at least one therapeutic agent selected from but not limited to the group comprising of a mitotic inhibitor, an anti-metabolite, and an alkylating agent; and opioid growth factor; and a carrier. 
     
     
         25 . The pharmaceutical composition of  claim 23  wherein said chemotherapeutic agent is selected from the group comprising but not limited to: busulfan, cisplatin, carboplatin, chlorambucil, cyclophosphamide, ifosfamide, dacarbazine {DTIC), mechlorethamine (nitrogen mustard), and melphalan. 5-fluorouracil, capecitabine, methotrexate, gemcitabine, cytarabine (ara-C), and fludarabine, paclitaxel, docetaxel, etoposide (VP-16), vinblastine, vincristine, and vinorelbine.