Kinase inhibitor prodrug for the treatment of cancer
Compositions containing and methods of administering TH-4000 are useful in treatment of cancer alone or in combination with other anti-cancer agents.
1. A method of treating cancer in a subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of a compound, [(E)-4-[[4-(3-bromo-4-chloroanilino)pyrido[3,4-d]pyrimidin-6-yl]amino]-4-oxobut-2-enyl]-dimethyl-[(3-methyl-5-nitroimidazol-4-yl)methyl]azanium bromide,
wherein said cancer is characterized by wild-type activity of the EGFR protein.
2. The method of claim 1 , wherein the amount of the compound administered is in the range of about 20 mg/m 2 to about 150 mg/m 2 .
3. The method of claim 1 , wherein the compound is administered intravenously.
4. The method of claim 1 , wherein the compound is administered at a frequency in the range of at least once per day to once per month.
5. The method of claim 1 , wherein the compound is administered at a frequency of about once every three days.
6. The method of claim 1 , wherein the compound is administered for a period of about 1 to about 60 weeks.
7. The method of claim 5 , wherein the compound is administered about once every three days for about 24 days.
8. The method of claim 1 , wherein the compound is administered over an infusion period of about 1 to about 6 hours.
9. The method of claim 1 , wherein the cancer is relapsed or refractory or the patient is unsuitable for standard chemotherapy.
10. The method of claim 1 , wherein the patient is also treated with erlotinib and/or cetuximab.
11. The method of claim 1 , wherein the cancer treated is non-small cell lung cancer.
12. The method of claim 1 , wherein the cancer treated is squamous cell cancer of the head and neck or skin.
13. The method of claim 1 , wherein the compound is administered in a dosage unit comprising a pharmaceutically acceptable formulation of the compound.
14. The method of claim 13 , wherein the pharmaceutically acceptable formulation comprises the compound or a pharmaceutically acceptable salt or solvate thereof and 2-hydroxylpropyl-3-cyclodextrin.
15. The method of claim 14 , wherein the dosage unit comprises about 75 to about 150 mg of the compound.
16. The method of claim 1 , wherein the compound is administered in a dose of about 150 mg/m 2 .
17. The method of claim 1 , wherein the cancer is heterozygous for the EGFR protein.
18. The method of claim 17 , wherein the cancer is characterized by a genotype comprising one mutant EGFR allele and one wild-type EGFR allele.
19. The method of claim 1 , wherein the cancer is homozygous for wild-type activity of the EGFR protein.
20. The method of claim 1 , wherein the activity of the wild-type EGFR protein is overexpressed or upregulated.
21. The method of claim 1 , wherein the expressed EGFR protein has a wild-type active site.
22. The method of claim 21 , wherein the cancer is characterized by at least one copy of Exon 19 of the EGFR gene.
23. The method of claim 1 , wherein the compound is administered in a dose of about 32 mg/m 2 .
24. The method of claim 1 , wherein the compound is administered in a dose of about 20 mg/m 2 .