NEW CHEMOTHERAPEUTIC-AGENTS IN ACUTE MYELOID-LEUKEMIA

Only two classes of chemotherapeutic agents have shown activity in acu te myeloid leukemia (AML): ara-C and topoisomerase II reactive agents. Frontline combinations of these agents produce complete response (CR) rates of 70% and longterm event-free survival rates of 25%. New agent s with different mechanisms of action are being explored. Nucleoside a nalogs such as chlorodeoxyadenosine (2-CdA) or fludarabine have shown single-agent efficacy and may be synergistic with ara-C. Combination t herapy with ara-C and nucleoside analogs have shown promising results both as salvage therapy and in newly diagnosed patients. Combinations of topotecan with ara-C, VP16, and anthracyclines are being pursued, a s is testing of other Topo-l inhibitors. Hypomethylating agents (5-aza cytidine, decitabine) are showing activity in AML, producing CR rates of 5% to 30% as AML salvage therapy as a single agent, and 40%-60% in combinations. Decitabine may be synergistic with topo I inhibitors, bi ologic agents, and differentiating agents. Homoharringtonine has modes t anti-AML activity, with CR rates of 10% to 30% as salvage therapy. O ther classes of agents worthy of continuing investigation are platinum analogs and agents with novel mechanisms of action such as tallimusti ne.