Methods for treating thrombocytopenia
The disclosure provides methods for treating, controlling or mitigating leukopenia (e.g. neutropenia) and/or thrombocytopenia, for example in the context of cancer chemotherapy, comprising administration of a monoacetyl-diacyl-glycerol compound, as well as compositions useful therefor.
1. A method for treating myelosuppressive chemotherapy-induced thrombocytopenia, comprising administering to a human in need thereof an effective amount of a compound of Formula 2:
wherein a platelet number of the human does not decrease to less than 25,000/μl.
2. The method of claim 1 , wherein the compound of Formula 2 is administered in a pharmaceutical composition, which is substantially free of other monoacetyl diacyl glycerol compounds.
3. The method of claim 2 , wherein the compound of Formula 2 is administered in a pharmaceutical composition, which is substantially free of triglyceride compounds.
4. The method of claim 1 , wherein the myelosuppressive chemotherapy-induced thrombocytopenia is caused by a drug selected from among Ziv-aflibercept, Brentuximab vedotin, Pralatrexate, Ganciclovir, Valganciclovir, Romidepsin, Ruxolitinib, Decitabine, Imatinib, Topotecan, Lenalidomide, Irinotecan, Interferons, Phenylhydrazine, Tamoxifen, Lipopolysaccharide, Anthracycline antibiotics, daunorubicin, doxorubicin, Gemcitabine, Cytoxan, Paclitaxel, Alkylating antineoplastic agent, DNA intercalating agent, Alkylating agent, bendamustin, mustard, Topoisomerase inhibitor, Bortezomib, Temsirolimus, Vorinostat, Ifosfamide, and Ixabepilone.
5. The method of claim 1 , wherein the human receives a chemotherapeutic agent selected from one or more of cyclophosphamide, doxorubicin, etoposide, ifosfamide, mesna, cisplatin, gemcitabine, tamoxifen and lenalidomide.
6. The method of claim 5 wherein the chemotherapeutic agent is lenalidomide.
7. The method of claim 1 , wherein the human has multiple myeloma, chronic myelogenous leukemia (CML), acute myeloid leukemia, or myelodysplastic syndrome.
8. The method of claim 1 , further comprising administering a G-CSF to the patient.
9. The method of claim 8 , wherein the patient suffers from thrombocytopenia due to treatment with one or more chemotherapeutic agents selected from cyclophosphamide, doxorubicin, etoposide, ifosfamide, mesna, cisplatin, gemcitabine, and tamoxifen.
10. The method of claim 8 , wherein the G-CSF is selected from filgrastim, pegfilgrastim, and lenograstim.
11. The method of claim 10 , wherein the G-CSF is filgrastim.
12. The method of claim 1 , wherein administering the compound of Formula 2 suppresses upregulated or activated Complement 3 (C3).
13. The method of claim 2 , wherein the pharmaceutical composition is formulated into solid, liquid, gel or suspension form for oral or non-oral administration.
14. The method of claim 13 , wherein the compound of Formula 2 is administered in the form of a pharmaceutical composition for oral administration.
15. The method of claim 14 wherein the compound of Formula 2 is administered in the form of a pharmaceutical composition which is a soft gelatin capsule containing the compound of Formula 2 in combination or association with a pharmaceutically acceptable diluent or carrier.
16. The method of claim 15 , wherein the total daily dosage of the compound of Formula 2 is 250 mg to 2000 mg.
17. The method of claim 16 wherein the composition further comprises a pharmaceutically acceptable antioxidant.
18. The method of claim 17 , wherein the pharmaceutically acceptable antioxidant is selected from ascorbic acid (AA, E300), tocopherols (E306), propyl gallate (PG, E310), tertiary butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA, E320) and butylated hydroxytoluene (BHT, E321).
19. The method of claim 18 , wherein the compound of formula 2 is administered in the form of a soft gelatin capsule for oral administration containing 250-1000 mg of a compound of Formula 2, substantially free of triglycerides, together with 0.1-3 mg of a pharmaceutically acceptable tocopherol compound.
20. The method of claim 19 , wherein the compound of formula 2 is administered in the form of a soft gelatin capsule for oral administration containing about 500 mg of a compound of Formula 2, substantially free of triglycerides, together with about 1 mg of a pharmaceutically acceptable tocopherol compound, administered once or twice a day.
21. The method of claim 1 , wherein the platelet count of the human does not decrease more than 70 percent.
22. The method of claim 1 , wherein STAT6 activity is reduced upon administering the compound of Formula 2.
23. The method of claim 1 wherein the total daily dosage of the compound of Formula 2 is 1000 mg to 2000 mg.
24. The method of claim 1 wherein a platelet number of the human does not decrease to less than 50,000/μl.