FIXED DRUG RATIOS FOR TREATMENT OF HEMATOPOIETIC CANCERS AND PROLIFERATIVE DISORDERS
Provided herein are methods for treating cancer by administering a pharmaceutical composition comprising a fixed, non-antagonistic molar ratio of cytarabine and an anthracycline. Such methods are particularly useful in the treatment of patients with advanced hematologic cancers or proliferative disorders.
1 . A method to treat cancer or hematologic proliferative disorder in a subject,
said method comprising intravenously administering a composition comprising a fixed, non-antagonistic molar ratio of cytarabine and daunorubicin over a period of 12 hours or less,
wherein said fixed ratio is maintained in the plasma for at least 4 hours, and
wherein said fixed, non-antagonistic molar ratio of cytarabine and daunorubicin is encapsulated in liposomes.
2 . The method of claim 1 wherein the composition is administered in 8 hours or less.
3 . The method of claim 2 wherein the composition is administered in 3 hours or less.
4 . The method of claim 3 , wherein said composition is administered in 90 minutes or less.
5 . The method of claim 1 , wherein said fixed, non-antagonistic molar ratio of cytarabine to daunorubicin is between about 1:1 to 25:1.
6 . The method of claim 5 , wherein said fixed, non-antagonistic molar ratio is about 5:1.
7 . The method of claim 1 , wherein cytarabine is administered at a dose not greater than 250 mg/m 2 .
8 . The method of claim 1 , wherein said liposomes comprise DSPC, DSPG and cholesterol.
9 . The method of claim 8 , wherein said liposomes comprise DSPC:DSPG:cholesterol at a mol ratio of 7:2:1.
10 . (canceled)
11 . The method of claim 1 , wherein the dose of said composition is 32-134 units per m 2 , wherein 1 unit is 1 mg cytarabine and 0.44 mg daunorubicin.
12 . The method of claim 1 , wherein said administration is by IV drip.
13 . The method of claim 1 , wherein the cancer or hematologic proliferative disorder is an advanced hematologic cancer, selected from acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL), and said hematologic proliferative disorder is myelodysplastic syndrome (MDS).
14 . The method of claim 1 , wherein said subject has previously undergone at least one anti-cancer regimen, and/or has previously experienced a remission.
15 . The method of claim 14 wherein said subject has experienced a relapse within 18 months after said anticancer regimen.
16 . The method of claim 15 wherein said subject has experienced a relapse within 6 months after said anticancer regimen.
17 . The method of claim 1 , which further includes measuring a therapeutic effect as a function of increase in complete remission rate, and/or as a function of prolongation of complete remission duration and/or prolongation of time to progression and/or prolongation of survival.
18 . (canceled)
19 . The method of claim 1 , which further includes measuring an improved safety result as a reduction in non-hematopoietic toxicities.
20 . The method of claim 19 , wherein the non-hematopoietic toxicities are mucositis and/or alopecia.
21 . (canceled)