Etoposide in leukemia. Etoposide (VP16-213, NSC 141540) induces a complete response (CR) in 15% to 25% of previously treated patients with acute nonlymphocytic leukemia (ANLL) when used as a single agent. Etoposide has been used successfully in combination with cytarabine, daunorubicin, and amsacrine for salvage and consolidation therapies. Previously untreated ANLL patients 15 to 70 years of age were randomly assigned to cytarabine (100 mg/m2) on days 1 to 7 plus daunorubicin (50 mg/m2) on days 1 to 3 (7-3) or to the same drugs plus etoposide (75 mg/m2) on days 1 to 7 (7-3-7). Patients achieving a CR received two consolidation courses (5-2, attenuated 7-3 or 5-2-5). Among 264 eligible patients, there was a 56% CR rate with 7-3 therapy and a 59% CR rate with 7-3-7 therapy. Remission duration was significantly improved with 7-3-7 (median, 12 months with 7-3 and 18 months with 7-3-7; P = 0.01), but survival was not. Subset analysis in patients younger than 55 years of age revealed prolonged remission (median, 12 months with 7-3 and 27 months with 7-3-7; P = 0.01) and survival (median, 9 months with 7-3 and 17 months with 7-3-7; P = 0.04) with the 7-3-7 regimen. Hematologic toxicity was similar for both regimens during induction, but significantly more severe for 7-3-7 during consolidation therapy. Etoposide is active in ANLL and prolongs remission when used in induction therapy. 