Anticancer treatment with a combination of taxanes and 13-deoxyanthracyclines
A 13-deoxy anthracycline and a taxane can be administered to a patient simultaneously, separately, sequentially, or consecutively to produce a therapeutic anticancer effect with reduced toxicity and side effect profile, compared to the administration of equieffective amounts of either compound alone. A composition or preparation of a 13-deoxy anthracyclines and a taxane for producing a potent anticancer therapeutic effect is also provided.
1. A therapeutically effective amount of a synergistic combined preparation comprising a first compound and a second compound, wherein:
the first compound is a 13-deoxyanthracycline, or pharmaceutically acceptable salts or prodrugs thereof, said 13-deoxyanthracycline having the formula:
wherein
each of R 1 , R 2 and R 3 is independently selected from the group consisting of H and OH;
R 4 is selected from the group consisting of H, OH, alkyl, and O-alkyl;
R 5 is selected from the group consisting of O and NH; and
R 6 is a sugar moiety; and
the second compound is a taxane;
wherein said therapeutically effective amount suppresses the growth of cells.
2. The preparation of claim 1 , wherein said 13-deoxyanthracycline is selected from the group consisting of 13-deoxydoxorubicin, 13-deoxydaunorubicin, 13-deoxycaminomycin, 13-deoxyepirubicin, 13-deoxyidarubicin, 13-deoxyannamycin, 13-deoxyamrubicin and the 5-imino analogs thereof, and said taxane is selected from the group consisting of paclitaxel and docetaxel.
3. A pharmaceutical composition comprising the preparation of claim 1 , and a pharmaceutically acceptable carrier or excipient.
4. A pharmaceutical composition comprising the preparation of claim 2 , and a pharmaceutically acceptable carrier or excipient.
5. The preparation of claim 1 , wherein said sugar moiety is selected from the group consisting of daunosamine, epidaunosamine, and a rhamnal sugar.
6. A therapeutically effective amount of a synergistic combined preparation comprising a first compound and a second compound, wherein:
the first compound is a 5-imino-13-deoxy anthracycline, or pharmaceutically acceptable salts or prodrugs thereof, said 5-imino-13-deoxy anthracycline having the formula:
wherein
each R 1 , R 2 and R 3 is independently selected from the group consisting of H and OH;
R 4 is selected from the group consisting of H, OH, alkyl, and O-alkyl;
R 5 is a sugar moiety; and
the second compound is a taxane;
wherein said therapeutically effective amount suppresses the growth of cells.
7. The preparation of claim 6 , wherein said 5-imino-13-deoxy anthracycline is selected from the group consisting of 5-imino-13-deoxydoxorubicin, 5-imino-13-deoxydaunorubicin, 5-imino-13-deoxycaminomycin, 5-imino-13-deoxyepirubicin, 5-imino-13-deoxyidarubicin, 5-imino-13-deoxyannamycin, and 5-imino-13-deoxyamrubicin, and said taxane is selected from the group consisting of paclitaxel and docetaxel.
8. A pharmaceutical composition comprising the preparation of claim 6 , and a pharmaceutically acceptable carrier or excipient.
9. A pharmaceutical composition comprising the preparation of claim 8 , and a pharmaceutically acceptable carrier or excipient.
10. The preparation of claim 6 , wherein said sugar moiety is selected from the group consisting of daunosamine, epidaunosamine, and a rhamnal sugar.
11. The preparation of claim 1 wherein said first compound is present in an amount that is lower than its therapeutically effective amount.
12. The preparation of claim 6 wherein said first compound is present in an amount that is lower than its therapeutically effective amount.