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
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.