Methods of using (+)-1,4-dihydro-7-[(3s,4s)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid for treatment of cancer

Abstract

Methods of treating, preventing or managing cancer, including certain leukemias are disclosed. The methods encompass the administration of enantiomerically pure (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid. Also provided are methods of treatment using this compound with chemotherapy, radiation therapy, hormonal therapy, biological therapy or immunotherapy. Pharmaceutical compositions and single unit dosage forms suitable for use in the methods are also disclosed.

1 - 51 . (canceled) 
     
     
         52 . A method of treating leukemia, comprising administering to a human from about 50 to about 100 mg/m 20 f an enantiomerically pure (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid, wherein the leukemia is a chronic lymphocytic leukemia, chronic myelogenous leukemia, acute lymphoblastic leukemia or acute myelogenous leukemia. 
     
     
         53 . A method of treating acute myelogenous leukemia comprising administering a dose of about 50 mg/m 2  to about 100 mg/m 2  of (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid and a therapeutically effective dose of a second agent to a human having acute myelogenous leukemia. 
     
     
         54 . The method of  claim 53 , wherein the acute myelogenous leukemia is a myeloblastic leukemia or promyelocytic leukemia. 
     
     
         55 . The method of  claim 53 , wherein the leukemia is relapsed, refractory or resistant to therapy selected from surgery, chemotherapy, radiation therapy, hormonal therapy, biological therapy, immunotherapy, blood transfusions, and combinations thereof. 
     
     
         56 . The method of  claim 53 , wherein the dose of (+)-1,4-dihydro-7-[(3 S,4 S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid is from 50 mg/m 2  to 90 mg/m 2 . 
     
     
         57 . The method of  claim 53 , wherein the dose of (+)-1,4-dihydro-7-[(3 S,4 S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid is from 80 mg/m 2  to 90 mg/m 2 . 
     
     
         58 . The method of  claim 53 , wherein the dose of (+)-1,4-dihydro-7-[(3 S,4 S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid is from 85 mg/m 2  to 95 mg/m 2 . 
     
     
         59 . The method of  claim 53 , wherein the dose of (+)-1,4-dihydro-7-[(3 S,4 S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid is from 90 mg/m 2  to 100 mg/m 2 . 
     
     
         60 . The method of  claim 53 , wherein (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid is administered as an IV injection. 
     
     
         61 . The method of  claim 53 , wherein (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid is administered in an IV push of 10-15 minutes duration. 
     
     
         62 . The method of  claim 53 , wherein the second agent is selected from the group consisting of an alkylating agent, an anti-neoplastic agent, an anti-metabolite, a platinum coordination complex, a topoisomerase II inhibitor, and radiation. 
     
     
         63 . The method of  claim 62 , wherein the anti-metabolite is selected from the group consisting of a folate analog, purine analog, adenosine analog, pyrimidine analog, and substituted urea. 
     
     
         64 . The method of  claim 62 , wherein the second agent is selected from the group consisting of azacitidine, decitabine, busulfan, chlorambucil, cyclophosphamide, melphalan, carmustine, bleomycin, dactinomycin, daunorubicin, daunorubicin hydrochloride, doxorubicin, doxorubicin hydrochloride, methotrexate, pemetrexed, mercaptopurine, thioguanidine, cladribine, pentostatin, cytarabine, capecitabine, fluorouracil, hydroxyurea, carboplatin, cisplatin, oxaliplatin, etoposide, teniposide, and vincristine sulfate. 
     
     
         65 . The method of  claim 62 , wherein the second agent is selected from the group consisting of azacitidine, decitabine, cyclophosphamide, daunorubicin, daunorubicin hydrochloride, doxorubicin, doxorubicin hydrochloride, cytarabine, etoposide, and vincristine sulfate.