[Combined therapy with AMSA and etoposide (VP 16-213) in refractory acute myeloid leukemia. A phase I study]

In a phase I study the combination of AMSA and etoposide was applied to 12 patients with intensively pretreated, refractory AML to evaluate the basis for a subsequent phase II study in terms of drug dosage and timing. Each treatment cycle consisted in a 5-day regimen of AMSA 210 mg/m2/d days 2, 3 and 4. Etoposide was administered on days 1 and 5 with a constant loading dose of 100 mg/m2 by an 1-h infusion followed by a 23-h infusion, the dose of which was escalated in 3 steps from 110 mg/m2 to 200 mg/m2 and 230 mg/m2. In 18 treatment cycles the recommended dosage for a subsequent phase II study was found to be 660 mg/m2 etoposide per cycle together with 630 mg/m2 AMSA per course. Main side effects were nausea and vomiting as well as mucositis; 1 patient developed a severe intrahepatic cholestasis. In 11 from 16 evaluable treatment cycles a significant reduction of bone marrow blasts was observed with a mean cytoreduction rate of 0,26 log10/d. 4 patients, 3 of whom were primarily resistent to 2 TAD induction courses, achieved a partial remission.