Treatment for melanoma
View Patent ↗The present invention relates to combination therapies for melanoma, and in particular, metastatic melanoma. Drugs for use in such therapies in include MEK inhibitors combination with cardiac glycosides.
1. A method of inhibiting melanoma in a subject comprising administering to said subject:
(a) trametinib; and
(b) a cardiac glycoside selected from digoxin and digitoxin, in an amount sufficient to inhibit said melanoma.
2. The method of claim 1 , wherein said subject is a human.
3. The method of claim 1 , wherein said subject is a non-human mammal.
4. The method of claim 1 , wherein inhibiting comprises inhibiting the growth of primary melanomas, inhibiting metastasis, inhibiting the growth of metastases, killing circulating melanoma cells, inducing remission, extending remission, or inhibiting recurrence.
5. The method of claim 1 , wherein said melanoma is AJCC stage III or stage IV disease.
6. The method of claim 1 , wherein said subject has previously received a radiotherapy, a chemotherapy, an immunotherapy, a molecularly targeted therapy or had surgical resection of a tumor.
7. The method of claim 1 , wherein trametinib is administered before or after the cardiac glycoside therapy.
8. The method of claim 1 , wherein trametinib is administered at the same time as the cardiac glycoside therapy.
9. The method of claim 1 , wherein trametinib and/or cardiac glycoside is administered more than once.
10. The method of claim 1 , wherein said cardiac glycoside is digoxin.
11. The method of claim 1 , wherein administering comprises topical, intravenous, intraarterial, subcutaneous, oral or intra-tumoral administration.
12. The method of claim 1 , wherein administering comprises local, regional or systemic administration.
13. The method of claim 1 , wherein administering comprises continuous infusion over a period of time.
14. The method of claim 1 , wherein said subject has failed one or more standard melanoma therapies.
15. The method of claim 1 , wherein said cardiac glycoside is digitoxin.
16. The method of claim 1 , wherein said amount sufficient to inhibit said melanoma is (a) less than the amount required for inhibition by either single agent alone, or (b) less toxic than the amount required for inhibition by either single agent alone.
17. The method of claim 1 , further comprising treating said subject with an additional agent.
18. The method of claim 17 , wherein said additional agent is an immunomodulator.
19. The method of claim 18 , wherein said immunomodulator is an antibody against PD1 or CTLA4, imiquimod, IL-2 or interferon.
20. The method of claim 17 , wherein said additional agent is a chemotherapeutic agent.
21. The method of claim 1 , further comprising excising a melanoma lesion.
22. The method of claim 21 , wherein excising occurs prior to or after trametinib/cardiac glycoside treatment.
23. The method of claim 21 , wherein excising occurs concurrent with trametinib/cardiac glycoside treatment.
24. The method of claim 1 , wherein said melanoma is BRAF wild-type.
25. The method of claim 1 , wherein said melanoma is BRAF mutated.
26. The method of claim 25 , wherein the BRAF mutation is V600E or V600K.