A targeted drug that is active against acute myeloid leukemia (AML) is particularly effective when teamed with chemotherapy in patients whose cancer cells harbor a key genetic mutation, researchers at Dana-Farber Cancer Institute and their colleagues will report at the American Society of Hematology's (ASH) annual meeting on Monday, Dec. 7 (Ernest N. Morial Convention Center, Room 343-345, 5:15 pm CT).
The Phase I study focused on the potential of administering the drug midostaurin (PK412) with high doses of the chemotherapy drug cytarabine in AML patients whose disease has been driven into remission by cytarabine and another chemotherapy agent, daunorubicin.
Midostaurin is a kinase inhibitor, blocking a key class of enzymes - kinases - that often spur cancer cell growth. It works by targeting the FLT3 cell receptor, which is overactive in the white blood cells of many AML patients as a result of genetic mutation.
On its own, midostaurin reduces the number of circulating leukemia cells in AML patients, but rarely produces complete remissions. Preclinical studies have shown that FLT3 inhibitors like midostaurin work synergistically with chemotherapy agents, reinforcing each other's effect against cancer.
In the new study, researchers led by Richard Stone, MD, of Dana-Farber treated 40 newly diagnosed AML patients under age 61 with daunorubicin and cytarabine to induce remission, followed by high-dose cytarabine and oral midostaurin in twice-daily doses of either 100 mg or 50 mg. The higher dose level often produced nausea and vomiting, but patients at the lower dosage tolerated the therapy well.