Compositions and methods for treating patients suffering from glioma or leukemia
Pharmaceutical compositions, kits and methods for treating tumors such as glioma and cancers such as leukemia with (R)-2-hydroxyglutarate (R-2HG) are provided, along with therapeutic regimens including treatment of a patient suffering from glioma or leukemia with a MYC-signaling inhibitor followed by or cotemporaneous with treatment with R-2HG, and optionally other chemotherapeutic agents.
1. A pharmaceutical composition comprising:
R-2-hydroxyglutarate (R-2HG);
one or more chemotherapeutic agents selected from the group consisting of all trans retinoic acid (ATRA), azacitidine (AZA), daunorubicin, and decitabine; and
a pharmaceutically-acceptable carrier.
2. The pharmaceutical composition of claim 1 , further comprising at least one agent that inhibits MYC signaling.
3. The pharmaceutical composition according to claim 2 wherein the at least one agent that inhibits MYC signaling is selected from the agents set forth in Table 4.
4. The pharmaceutical composition according to claim 1 , wherein the R-2HG comprises ester-modified R-2HG.
5. The pharmaceutical composition according to claim 1 , formulated as an injectable suspension.
6. The pharmaceutical composition according to claim 5 , wherein the R-2HG is present in the suspension in a concentration of between about 10 μM and 500 μM, 50 μM and 400 μM, 100 μM and 300 μM, 150 μM and 250 μM, or about 200 μM R-2HG by weight, and is administered in a dose of about 1-10 mg R-2HG per kg body weight.