Etoposide in acute leukemia. Past experience and future perspectives. Etoposide as a single agent is active in relapsed and refractory acute myelogenous leukemia (AML), with complete responses (CR) rates of 10% to 25%. The drug has been safely combined with cytarabine, azacytidine, vinca alkaloids, and anthracyclines, inducing remission rates of 20% to 60% in patients with previously treated AML. The experience with etoposide in acute lymphoblastic leukemia is less extensive, but the drug seems to be active in combination with cytarabine or aclacinomycin. In addition, etoposide is combined with cytarabine and anthracyclines for the primary treatment of AML. The response rates thus achieved are comparable with those obtained with standard regimens. A Phase I/II trial was initiated to study the efficacy of the NOVE combination (mitoxantrone [10 mg/m2/d, days 1 to 5] plus etoposide [100 mg/m2/d for 3, 4, or 5 days] in patients with refractory AML. The results showed that extended duration of etoposide administration is associated with higher CR rates. Overall, a CR rate of 43% was achieved in 61 patients. A sequential regimen with IDAC (idarubicin/cytarabine) and NOVE was designed for primary treatment of adult patients with AML. Cycles of IDAC or NOVE are applied depending on response. The results of the pilot study with this strategy were encouraging with 18 of 20 patients achieving CR. Further studies are under way to verify the efficacy of this strategy. 