Combination methods for treating cancers
Disclosed are methods for treating a cancer in a subject (e.g., a human) in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of formula I: or a pharmaceutically acceptable salt thereof; in combination with a vinca-alkaloid, or a pharmaceutically acceptable salt thereof. The subject may be very high risk or high risk for the cancer and may not respond to either agent administered as a sole therapy. The subject who has the cancer may also be refractory to at least one chemotherapy treatment, or is in relapse after treatment with chemotherapy, or both. The cancer may be a hematologic malignancy, such as leukemia or lymphoma, or a solid tumor cancer, such as pancreatic, lung and colon cancer.
1. A method for treating cancer in a human in need thereof, comprising administering to the human a therapeutically effective amount of a compound of formula I:
or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of a vinca-alkaloid, or a pharmaceutically acceptable salt thereof; wherein the cancer is a hematologic malignancy.
2. A method for treating cancer in a human in need thereof, comprising administering to the human a therapeutically effective amount of a compound of formula I:
or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of a vinca-alkaloid, or a pharmaceutically acceptable salt thereof; wherein the cancer is a leukemia.
3. The method of claim 2 , wherein the leukemia is chronic lymphocytic leukemia (CLL).
4. A method for treating cancer in a human in need thereof, comprising administering to the human a therapeutically effective amount of a compound of formula I:
or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of a vinca-alkaloid, or a pharmaceutically acceptable salt thereof; wherein the cancer is a lymphoma.
5. The method of claim 4 , wherein the lymphoma is non-Hodgkin's lymphoma (NHL).
6. The method of claim 5 , wherein the NHL is diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL), and marginal zone lymphoma (MZL).
7. A method for treating cancer in a human in need thereof, comprising administering to the human a therapeutically effective amount of a compound of formula I:
or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of a vinca-alkaloid, or a pharmaceutically acceptable salt thereof; wherein the cancer is selected from the group consisting of acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), Burkitt's lymphoma (BL), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), myelodysplastic syndrome (MDS), myeloproliferative disease (MPD), chronic myeloid leukemia (CML), multiple myeloma (MM), non-Hodgkin's lymphoma (NHL), indolent non-Hodgkin's lymphoma (iNHL), refractory iNHL, mantle cell lymphoma (MCL), follicular lymphoma (FL), Waldestrom's macroglobulinemia (WM), T-cell lymphoma, B-cell lymphoma, Hodgkin's lymphoma, diffuse large B-cell lymphoma (DLBCL), lymphoplasmacytic lymphoma (LPL), and marginal zone lymphoma (MZL).
8. The method according to claim 1 wherein said vinca-alkaloid is vincristine, or a pharmaceutically acceptable salt thereof.
9. The method according to claim 2 wherein said vinca-alkaloid is vincristine, or a pharmaceutically acceptable salt thereof.
10. The method according to claim 3 wherein said vinca-alkaloid is vincristine, or a pharmaceutically acceptable salt thereof.
11. The method according to claim 4 wherein said vinca-alkaloid is vincristine, or a pharmaceutically acceptable salt thereof.
12. The method according to claim 5 wherein said vinca-alkaloid is vincristine, or a pharmaceutically acceptable salt thereof.
13. The method according to claim 6 wherein said vinca-alkaloid is vincristine, or a pharmaceutically acceptable salt thereof.
14. The method according to claim 7 wherein said vinca-alkaloid is vincristine, or a pharmaceutically acceptable salt thereof.
15. The method according to claim 1 wherein said hematologic malignancy is acute lymphocytic leukemia (ALL).
16. The method according to claim 1 wherein said hematologic malignancy is acute myeloid leukemia (AML).
17. The method according to claim 1 wherein said hematologic malignancy is Burkitt's lymphoma (BL).
18. The method according to claim 1 wherein said hematologic malignancy is small lymphocytic lymphoma (SLL).
19. The method according to claim 1 wherein said hematologic malignancy is myelodysplastic syndrome (MDS).
20. The method according to claim 1 wherein said hematologic malignancy is myeloproliferative disease (MPD).
21. The method according to claim 1 wherein said hematologic malignancy is chronic myeloid leukemia (CML).
22. The method according to claim 1 wherein said hematologic malignancy is multiple myeloma (MM).
23. The method according to claim 1 wherein said hematologic malignancy is non-Hodgkin's lymphoma (NHL).
24. The method according to claim 1 wherein said hematologic malignancy is indolent non-Hodgkin's lymphoma (iNHL).
25. The method according to claim 1 wherein said hematologic malignancy is refractory iNHL, mantle cell lymphoma (MCL).
26. The method according to claim 1 wherein said hematologic malignancy is follicular lymphoma (FL).
27. The method according to claim 1 wherein said hematologic malignancy is Waldestrom's macroglobulinemia (WM).
28. The method according to claim 1 wherein said hematologic malignancy is T-cell lymphoma.
29. The method according to claim 1 wherein said hematologic malignancy is B-cell lymphoma.
30. The method according to claim 1 wherein said hematologic malignancy is Hodgkin's lymphoma.
31. The method according to claim 1 wherein said hematologic malignancy is diffuse large B-cell lymphoma (DLBCL).
32. The method according to claim 1 wherein said hematologic malignancy is lymphoplasmacytic lymphoma (LPL).
33. The method according to claim 1 wherein said hematologic malignancy is marginal zone lymphoma (MZL).