Pulsatile Dosing of Gossypol for Treatment of Disease
This invention relates to pulsatile dose administration of gossypol, a gossypol-related compound or pharmaceutical compositions thereof for treating diseases, disorders and conditions responsive to gossypol or gossypol-related compound, inhibiting the activity of anti-apoptotic Bcl-2 family proteins, inducing apoptosis in cells and increasing the sensitivity of cells to inducers of apoptosis.
1 . A method of treating, ameliorating or preventing a disease, condition or disorder responsive to treatment with gossypol or a gossypol-related compound comprising administering to a patient in need thereof a therapeutically effective amount of said gossypol or gossypol-related compound by pulsatile dose administration.
2 - 8 . (canceled)
9 . The method of claim 1 , wherein said disease is a squamous cell cancer.
10 - 11 . (canceled)
12 . The method of claim 1 , wherein said patient suffers fewer and/or less severe adverse events compared to when said gossypol is administered daily.
13 . The method of claim 1 , wherein said gossypol or gossypol-related compound is (−)-gossypol.
14 . The method of claim 1 further comprising administering one or more anticancer agents to said patient.
15 . (canceled)
16 . The method of claim 15 claim 14 , wherein said one or more anticancer agents is selected from the group consisting of docetaxel, paclitaxel, topotecan HCl, erlotinib, lenalidomide, cisplatin, erbitux, and oxaliplatin.
17 - 21 . (canceled)
22 . The method of claim 1 , wherein said gossypol or gossypol-related compound is administered on at least two consecutive days followed by at least one day wherein said gossypol is not administered.
23 - 27 . (canceled)
28 . The method of claim 1 , comprising administering to a patient in need thereof (−)-gossypol in combination with an anticancer agent, wherein about 40 mg to about 60 mg of said (−)-gossypol is orally administered twice-a-day for three consecutive days followed by eighteen consecutive days wherein said (−)-gossypol is not administered.
29 - 32 . (canceled)
33 . The method of claim 1 comprising administering to a patient in need thereof (−)-gossypol wherein said (−)-gossypol is orally administered to said patient on day 1, day 2, and day 3 of a treatment cycle.
34 - 36 . (canceled)
37 . The method of claim 33 , further comprising administering to said patient wherein said disease is cancer an anticancer agent on day 1 of said treatment cycle.
38 - 39 . (canceled)
40 . The method of claim 37 , wherein:
a) said cancer is selected from the group consisting of non-small cell lung cancer and prostate cancer;
b) said treatment cycle is 21 days and is repeated one or more times; and
c) said anticancer agent is docetaxel.
41 . The method of claim 37 wherein:
a) said cancer is selected from the group consisting of breast cancer, non-small cell lung cancer, ovarian carcinoma, and Kaposi's sarcoma;
b) said treatment cycle is 21 days and is repeated one or more times; and
c) said anticancer agent is paclitaxel.
42 . The method of claim 37 , wherein:
a) said cancer is selected from the group consisting of multiple myeloma and chronic lymphocytic leukemia; and
b) said anticancer agent is lenalidomide.
43 . The method of claim 37 , wherein:
a) said cancer is laryngeal cancer; and
b) said anticancer agent is cisplatin.
44 . The method of claim 37 , wherein:
a) said cancer is selected from the group consisting of head and neck cancer and colorectal cancer; and
b) said anticancer agent is erbitux.
45 . The method of claim 37 , wherein:
a) said cancer is colorectal cancer;
b) said treatment cycle is 14 days and is repeated one or more times; and
c) said anticancer agent is oxaliplatin.
46 . The method of claim 37 , wherein:
a) said cancer is non-small cell lung cancer; and
b) said anticancer agent is erlotinib.
47 . The method of claim 37 further comprising administering said (−)-gossypol on day 4 and day 5 of said treatment cycle and:
a) said cancer is non-small cell lung cancer;
b) said treatment cycle is 21 days and repeated one or more times; and
c) said anticancer agent is topotecan HCl.
48 - 49 . (canceled)
50 . The method of claim 33 , wherein said cancer is non-small cell lung cancer and wherein:
a) about 40 mg of said (−)-gossypol is orally administered to said patient twice-a-day on day 1, day 2, and day 3 of a 21-day treatment cycle; and
b) docetaxel is intravenously administered to said patient on day 1 of said treatment cycle.
51 - 52 . (canceled)
53 . A method of reducing the number of one or more adverse events, the severity of one or more adverse events, or combination thereof, in a patient undergoing cancer therapy comprising administering gossypol or a gossypol-related compound to said patient.
54 - 58 . (canceled)