Combination treatment for acute myeloid leukemia (AML)
The present invention relates to a pharmaceutical product comprising a) as a first component an inhibitor of the MDM2-p53 interaction such as, for example: and b) as a second component cytarabine; as a combined preparation for the sequential or simultaneous use in the treatment of cancer.
1. A pharmaceutical product, comprising a) as a first component an inhibitor of the MDM2-p53 interaction; and b) as a second component cytarabine, wherein the inhibitor of the MDM2-p53 interaction is a compound of formula (I):
wherein n is from 3 to 70; or a compound of formula (A):
2. The pharmaceutical product according to claim 1 , wherein n is from 30 to 60.
3. A method for treating acute myeloid leukemia, said method comprising: administering to a patient in need thereof the product of claim 2 .
4. The pharmaceutical product according to claim 1 , wherein a is from 40 to 50.
5. A method for treating acute myeloid leukemia, said method comprising: administering to a patient in need thereof the product of claim 4 .
6. The pharmaceutical product according to claim 1 , wherein n is 41, 42, 43, 44, 46, 47, 48 or 49.
7. A method for treating acute myeloid leukemia, said method comprising: administering to a patient in need thereof the product of claim 6 .
8. The pharmaceutical product according to claim 1 , wherein the inhibitor of the MDM2-p53 interaction is 4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid 1-mPEG-carbonyloxy-ethyl ester (mPEG, average MW, ˜2000); or wherein the inhibitor of the MDM2-p53 interaction is 4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid 1-mPEG-carbonyloxy-ethyl ester (mPEG, average MW, ˜2200); or combinations thereof.
9. A method for treating acute myeloid leukemia, said method comprising: administering to a patient in need thereof the product of claim 8 .
10. The pharmaceutical product according to claim 1 , wherein the inhibitor of the MDM2-p53 interaction is the compound of formula (A)
11. A method for treating acute myeloid leukemia, said method comprising: administering to a patient in need thereof the product of claim 1 .
12. A pharmaceutical product, comprising, a) as a first component a compound of formula (I):
wherein n is from 3 to 70; and b) as a second component the compound cytarabine, wherein the dose of the compound of formula (I) corresponds to a dose of compound (A):
within the range from about 200 to about 1600 mg/day.
13. The pharmaceutical product according to claim 12 , wherein the compound of formula (I) is the compound 4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid 1-mPEG-carbonyloxy-ethyl ester (mPEG, average MW, ˜2000); or 4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid 1-mPEG-carbonyloxy-ethyl ester (mPEG, average MW, ˜2200); or combinations thereof.