Compositions including triciribine and trastuzumab and methods of use thereof
This application relates to combination therapies including triciribine and related compounds and trastuzumab or a salt thereof and compositions with reduced toxicity for the treatment and prevention of tumors, cancer, and other disorders associated with abnormal cell proliferation.
1. A method of treating a tumor or cancer that overexpressed AKT in a mammal comprising administering to the mammal an effective amount of a composition comprising:
(i) a compound of formula I:
wherein each R 2′ , R 3′ and R 5′ are independently hydrogen, optionally substituted phosphate or phosphonate; acyl; alkyl; amide, sulfonate ester including alkyl or arylalkyl; sulfonyl, methanesulfonyl, benzylsulfonyl; optionally substituted arylsulfonyl; a lipid, a phospholipid; an amino acid; a carbohydrate; a peptide; or cholesterol; or other pharmaceutically acceptable leaving group that, in vivo, provides a compound wherein R 2′ , R 3′ and R 5′ is independently H or mono-, di- or tri-phosphate;
wherein R x and R y are independently hydrogen, optionally substituted phosphate; acyl; amide, alkyl; aromatic, polyoxyalkylene such as polyethyleneglycol, optionally substituted arylsulfonyl; a lipid, including a phospholipid; an amino acid; a carbohydrate; a peptide; or cholesterol; or other pharmaceutically acceptable leaving group;
R 1 and R 2 each are independently H, optionally substituted straight chained, branched or cyclic alkyl, alkenyl, or alkynyl, CO-alkyl, CO-alkenyl, CO-alkynyl, CO-aryl or heteroaryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, sulfonyl, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl; and
(ii) trastuzumab or a salt thereof;
wherein the compound of formula I is administered to said mammal in an amount of at least 10 mg/m 2 .
2. The method of claim 1 , wherein a compound of formula I and trastuzumab or a salt thereof are administered simultaneously.
3. The method of claim 1 , wherein a compound of formula I is administered followed by the administration of trastuzumab or a salt thereof.
4. The method of claim 1 , wherein the trastuzumab or a salt thereof is administered followed by the administration of a compound of formula I.
5. The method of claim 1 , wherein the compound of formula I is administered one time per week for three weeks followed by a one-week period wherein the compound is not administered.
6. The method of claim 1 , wherein the trastuzumab or a salt thereof is administered one time per week for three weeks followed by a one-week period wherein the compound is not administered.
7. The method of claim 6 , wherein the dosing schedule is repeated at least twice.
8. The method of claim 6 , wherein the dosing schedule is repeated at least 4 times.
9. The method of claim 1 , wherein the tumor treated is breast, pancreatic, ovarian and colorectal tumors.
10. The method of claim 1 , wherein at least 100 mg of trastuzumab or a salt thereof is administered.
11. The method of claim 1 , wherein at least 200 mg of trastuzumab or a salt thereof is administered.
12. The method of claim 1 , wherein at least 400 mg of trastuzumab or a salt thereof is administered.