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 in combination therapy

Abstract

Methods of treating, preventing or managing cancers are disclosed. The methods encompass the administration of SNS-595 in combination with a second active agent. In certain embodiments, the method of treatment comprise administering SNS-595 in combination with cisplatin, carboplatin, gemcitabine or a combination thereof.

1 . A method of treating cancer comprising administering a dose of about 1 mg/m 2  to about 150 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/or a pharmaceutically acceptable salt or hydrate thereof and a dose of about 5 mg/m 2  to about 200 mg/m 2  cisplatin. 
     
     
         2 . The method of  claim 1 , wherein the dose 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/or a pharmaceutically acceptable salt or hydrate thereof is from about 10 mg/m 2  to about 90 mg/m 2 . 
     
     
         3 . The method of  claim 1 , wherein the dose 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/or a pharmaceutically acceptable salt or hydrate thereof is about 18 mg/m 2 . 
     
     
         4 . The method of  claim 1 , wherein the dose 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/or a pharmaceutically acceptable salt or hydrate thereof is about 48 mg/m 2 . 
     
     
         5 . The method of  claim 1 , wherein the dose 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/or a pharmaceutically acceptable salt or hydrate thereof is about 60 mg/m 2 . 
     
     
         6 . The method of  claim 1 , wherein the dose 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/or a pharmaceutically acceptable salt or hydrate thereof is about 75 mg/m 2 . 
     
     
         7 . The method of  claim 1 , wherein the dose of cisplatin is from about 20 mg/m 2  to about 100 mg/m 2 . 
     
     
         8 . The method of  claim 1 , wherein the dose of cisplatin is from about 50 mg/m 2  to about 70 mg/m 2  once every 4 weeks. 
     
     
         9 . The method of  claim 1 , wherein the dose of cisplatin is from about 75 mg/m 2  to about 100 mg/m 2  once every 4 weeks. 
     
     
         10 - 18 . (canceled) 
     
     
         19 . A method of treating cancer comprising administering a dose of about 1 mg/m 2  to about 150 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/or a pharmaceutically acceptable salt or hydrate thereof and a dose of about 50 mg/m 2  to about 400 mg/m 2  carboplatin. 
     
     
         20 . The method of  claim 19 , wherein the dose 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/or a pharmaceutically acceptable salt or hydrate thereof is from about 10 mg/m 2  to about 90 mg/m 2 . 
     
     
         21 . The method of  claim 19 , wherein the dose 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/or a pharmaceutically acceptable salt or hydrate thereof is about 18 mg/m 2 . 
     
     
         22 . The method of  claim 19 , wherein the dose 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/or a pharmaceutically acceptable salt or hydrate thereof is about 48 mg/m 2 . 
     
     
         23 . The method of  claim 19 , wherein the dose of (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid is about 60 mg/m 2 . 
     
     
         24 . The method of  claim 19 , wherein the dose 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/or a pharmaceutically acceptable salt or hydrate thereof is about 75 mg/m 2 . 
     
     
         25 . The method of  claim 19 , wherein the dose of carboplatin is from about 100 mg/m 2  to about 400 mg/m 2 . 
     
     
         26 . The method of  claim 19 , wherein the dose of carboplatin is about 300 mg/m 2  once every 3 to 4 weeks. 
     
     
         27 . The method of  claim 19 , wherein the dose of carboplatin is about 360 mg/m 2  once every 3 to 4 weeks. 
     
     
         28 . The method of  claim 1 , wherein the cancer is bladder cancer, breast cancer, cervical cancer, colon cancer, esophageal cancer, head and neck cancer, liver cancer, small cell lung cancer, non-small cell lung cancer, melanoma, myeloma, neuroblastoma, ovarian cancer, pancreatic cancer, prostate cancer, renal cancer, sarcoma, skin cancer, stomach cancer, testicular cancer, thyroid cancer or uterine cancer. 
     
     
         29 . The method of  claim 1 , wherein the cancer is ovarian cancer. 
     
     
         30 . The method of  claim 29 , wherein the cancer is relapsed, refractory or resistant to conventional therapy. 
     
     
         31 . The method of  claim 1 , further comprising administering a therapeutically effective amount of another active agent or a support care therapy. 
     
     
         32 . The method of  claim 31 , wherein the other active agent is a therapeutic antibody that specifically binds to a cancer antigen, hematopoietic growth factor, cytokine, anti-cancer agent, antibiotic, cox-2 inhibitor, immunomodulatory agent, immunosuppressive agent, corticosteroid or a pharmacologically active mutant or derivative thereof. 
     
     
         33 . The method of  claim 1 , wherein (+) 1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid and/or a pharmaceutically acceptable salt or hydrate thereof is administered once a week for three weeks. 
     
     
         34 . The method of  claim 1 , wherein (+) 1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid and/or a pharmaceutically acceptable salt or hydrate thereof administered once every three weeks. 
     
     
         35 . The method of  claim 1 , wherein (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid and/or a pharmaceutically acceptable salt or hydrate thereof is administered as an IV injection. 
     
     
         36 . The method of  claim 19 , wherein the cancer is bladder cancer, breast cancer, cervical cancer, colon cancer, esophageal cancer, head and neck cancer, liver cancer, small cell lung cancer, non-small cell lung cancer, melanoma, myeloma, neuroblastoma, ovarian cancer, pancreatic cancer, prostate cancer, renal cancer, sarcoma, skin cancer, stomach cancer, testicular cancer, thyroid cancer or uterine cancer. 
     
     
         37 . The method of  claim 19 , wherein the cancer is ovarian cancer. 
     
     
         38 . The method of  claim 37 , wherein the cancer is relapsed, refractory or resistant to conventional therapy. 
     
     
         39 . The method of  claim 19 , further comprising administering a therapeutically effective amount of another active agent or a support care therapy. 
     
     
         40 . The method of  claim 39 , wherein the other active agent is a therapeutic antibody that specifically binds to a cancer antigen, hematopoietic growth factor, cytokine, anti-cancer agent, antibiotic, cox-2 inhibitor, immunomodulatory agent, immunosuppressive agent, corticosteroid or a pharmacologically active mutant or derivative thereof. 
     
     
         41 . The method of  claim 19 , wherein (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid and/or a pharmaceutically acceptable salt or hydrate thereof is administered once a week for three weeks. 
     
     
         42 . The method of  claim 19 , wherein (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid and/or a pharmaceutically acceptable salt or hydrate thereof administered once every three weeks. 
     
     
         43 . The method of  claim 19 , wherein (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid and/or a pharmaceutically acceptable salt or hydrate thereof is administered as an IV injection.