Compounds and methods for treatment of chemotherapy-induced anemia

Abstract

The invention relates to methods and compounds for treating chemotherapy-induced anemia. In particular, methods for treating chemotherapy-induced anemia in subjects refractory to treatment with recombinant human erythropoietin are encompassed herein.

1 . A method for treating or preventing chemotherapy-induced anemia in a subject, the method comprising administering to the subject an effective amount of an agent that inhibits hypoxia inducible factor (HIF) hydroxylase activity, wherein the subject is refractory or is at risk for being refractory to recombinant human EPO therapy. 
   
   
       2 . A method for reducing or preventing weight-loss associated with chemotherapy in a subject, the method comprising administering to the subject an effective amount of an agent that inhibits hypoxia inducible factor (HIF) hydroxylase activity, wherein the subject is refractory or is at risk for being refractory to recombinant human EPO therapy. 
   
   
       3 . The method of  claim 1 , wherein the subject is undergoing chemotherapy. 
   
   
       4 . The method of  claim 1 , wherein the subject has undergone chemotherapy. 
   
   
       5 . The method of  claim 1 , wherein the subject is expected to under chemotherapy. 
   
   
       6 . The method of  claim 1 , wherein the chemotherapy comprises administration of a chemotherapeutic selected from the group consisting of: an alkylating agent; a nitrosoureas; an antimetabolite; an anthracyclines; a topoisomerase II inhibitor; a mitotic inhibitor; an anti-estrogen; a progestin; an aromatase inhibitor; an anti-androgen; an LHRH agonist; a corticosteroid hormone; a DNA alkylating agent; a taxane; a vince alkaloid; and a microtubule poison. 
   
   
       7 . The method of  claim 1 , wherein the chemotherapeutic is selected from the group consisting of busulfan, cisplatin, carboplatin, chlorambucil, cyclophosphamide, ifosfamide, dacarbazine (DTIC), mechlorethamine (nitrogen mustard), melphalan, temozolomide, carmustine (BCNU), lomustine (CCNU), 5-fluorouracil, capecitabine, 6-mercaptopurine, methotrexate, gemcitabine, cytarabine (ara-C), fludarabine, pemetrexed, daunorubicin, doxorubicin (Adriamycin), epirubicin, idarubicin, mitoxantrone, topotecan, irinotecan, etoposide (VP-16), teniposide, paclitaxel, docetaxel, vinblastine, vincristine, vinorelbine, prednisone, dexamethasone, L-asparaginase, dactinomycin, thalidomide, tretinoin, imatinib (Gleevec), gefitinib (Iressa), erlotinib (Tarceva), rituximab (Rituxan), bevacizumab (Avastin), tamoxifen, fulvestrant, anastrozole, exemestane, letrozole, megestrol acetate, bicalutamide, flutamide, leuprolide, and goserelin. 
   
   
       8 . The method of  claim 1 , wherein the agent is a 2-oxoglutarate mimetic. 
   
   
       9 . The method of  claim 1 , wherein the agent is administered orally, systemically, intravenously, or by injection.