Abstract

In a randomized study of acute myelocytic leukemia (AML), 352 patients of all ages were treated for remission induction by one of the four regimens: 7 days of cytosine arabinoside (ara-C) by continuous intravenous (i.v.) infusion or bolus injection every 12 hr, together with daunorubicin (DNR) by rapid i.v. injection on days 1, 2, 3; or 5 days of ara-C by infusion or bolus injection and DNR for 2 days only. The regimen of 7 and 3 infusion was significantly superior to the other 3 regimens, resulting in 56% complete remission (CR). For remission maintenance, ara-C was given for 5 days every month and each month one of the following four drugs added on a cyclic rotational basis: thioguanine, cyclophosphamide, CCNU, or DNR. Although ara-C dosage each month was the same, the route of ara-C administration by random allocation was either rapid i.v. bolus or subcutaneous (s.c.) injection. The median duration of CR was significantly longer for s.c. ara-C group: 14 mo for patients less than 60 yr old (versus 8 mo for i.v.) and 31 mo for 60 or older age group (versus 9 mo for i.v.). Patients who received a combination of the best of the four induction regimens (7 and 3 infusion) and the better of the two maintenance schedules (s.c. ara-C) had a median remission duration of 22 mo and a median survival of 35 mo (the longest reported in a prospective randomized trial of therapy for AML). These results establish the validity of an intensive chemotherapy to produce rapid marrow aplasia followed by a sequential maintenance therapy for achieving prolonged disease-free survival in AML.