Treatment of acute leukemia with idarubicin, etoposide and cytarabine (IDEA). A randomized study of etoposide schedule
The differences in toxicity of etoposide following continuous or bolus infusion are unknown. We studied the schedule-dependent toxicity of high-dose etoposide when combined with high-dose cytarabine and idarubicin (IDEA) in 138 patients with acute leukemia. Four groups of patients were studied: group I, relapse; group II, secondary acute myeloid leukemia (AML); group III, de novo AML, age >60 years; and group IV, induction failure or blast crisis of myeloproliferative syndrome. Treatment for groups I–III was idarubicin 8 mg/m2 per day days 1–3, cytarabine 2000 mg/m2 once a day days 1–6, and etoposide 1600 mg/m2 total dose. Group IV treatment differed by cytarabine given twice daily days 1–6. Patients were randomized to etoposide as a continuous infusion days 1–6 or as a bolus infusion over 10 h on day 7. Continuous infusion etoposide produced significantly more oral mucositis than bolus etoposide. In groups I–III, comparing continuous and bolus etoposide, there was a median of 3 vs 0 days of grade 2 or more oral mucositis (P<0.0001) and 13.5 vs 0 days of total parenteral nutrition (TPN) (P=0.0003). Group IV patients had a median 7 vs 0 days of grade 2 or more oral mucositis (P<0.01) and 21 vs 7 days of TPN (P<0.003), respectively. There were no differences in hematologic recovery, length of hospital stay, complete remission rate or overall survival between the two etoposide schedules. Of groups I–III patients, 51% achieved complete remission, and 11% died from treatment-related complications. The toxicity profile of high-dose etoposide is schedule-dependent with prolonged exposure producing significantly more non-hematologic toxicity.