High-dose ara-C and etoposide in refractory or relapsing acute leukemia

Summary A total of 32 patients (15 men and 17 women) presenting with relapsing or refractory acute leukemia were treated with a 3-h infusion of 3 g/m² cytosine arabinoside (ara-C) twice daily on days 1–6 and a 1-h infusion of 100 mg/m² etoposide on days 1–5. In all, 6 subjects had acute lymphocytic leukemia (ALL); 25 had acute myeloid leukemia (AML) of types M1 (n=6), M2 (n=10), M4 (n=5), and M5 (n=4); and 1 had mixed-type leukemia. The median age was 35 years (ranges, 16–62 years). Of the patients presenting with AML, 11 were primarily refractory and 3 became refractory after their first relapse. Six subjects had an early first relapse following a complete remission (CR) that lasted <6 months and five, a second relapse. Another patient underwent a primary relapse after >6 months but had been heavily pretreated. In all, 5 subjects with refractory AML achieved a CR [36%; 95% confidence interval (CI), 10%–62%) as did 7 patients exhibiting relapsing AML (58%; CI, 30%–86%). Three patients who had relapsing or resistant ALL achieved a CR. Side effects consisted of severe hematotoxicity associated with granulocytopenia of <500/mm³ that lasted for a mean of 23.6 days and thrombocytopenia of <20,000/mm³ whose mean duration was 20.8 days. Marked gastrointestinal toxicity and infections were also prevalent. Cutaneous and ocular toxicity as well as allergic, pulmonary and cerebellar side effects were observed in a few cases. We conclude that the combination of high-dose ara-C and etoposide is a powerful but toxic induction regimen for refractory or relapsed acute leukemia.