A comparative trial of daunorubicin, cytosine arabinoside, and thioguanine, and a combination of the three agents for the treatment of acute myelocytic leukemia

Abstract

In this study 523 previously untreated patients with acute myelocytic leukemia were randomly allocated to induction therapy with daunorubicin 60 mg/M2 daily X 3, cytosine arabinoside and thioguanine 100 mg/M2 each every 12 hours until marrow hypoplasia was achieved, or a 5-day course of the three drugs with daunorubicin 100 mg/M2 given on dav 1 and cytosine arabinoside plus thioguanine each given at a dose of 100 mg/M2 every 12 hours for five days. All patients received cyclophosphamide 600 mg/M2 followed in 24 hours by hydroxyurea 500 mg/M2 every six hours for four doses monthly for maintenance therapy. Patients were randomized to receive one of three antimetabolite treatments beginning 24 hours after the last dose of hydroxyurea each month for seven days. One such treatment consisted of 6-mercaptopurine 100 mg/M2 daily, another group received 6-thioguanine at the same dose daily, and the third group received 50 mg/M2 of both antimetabolites daily. There were no significant differences in complete response rate, remission duration, or survival among the various treatment groups.

Treatment of patients with acute nonlymphocytic leukemia in relapse: A leukemia intergroup study

“…Death during induction (other failures) was twice as common a cause of induction failure as was clinically documented drug-resistant disease. The 4.5-month median duration of unmaintained remission achieved in the present study is reminiscent of earlier trials in which patients received inadequate consolidation/maintenance therapies and attained remission durations of only several months [2,10,11]. It is of interest that in spite of the short median duration of remission, two patients attained remission durations of greater than 90 weeks, suggesting that there exists a subset of patients who do not require any therapy after entering remission and who nevertheless attain prolonged remission durations.…”

Clinical course and response to treatment of patients with acute myelogenous leukemia presenting with a high leukocyte count

“…There has been substantial improvement in the treatment of patients with AML over the last decade, with reported remission rates of 58% to 90%.". 12 The impact of such improved treatments on patients with high leukocyte counts is not established, and it is not known to what degree extreme leukocytosis is still a significant adverse prognostic factor. Since the currently available therapeutic agents are effectively applied to the management of leukemia in adults, identification of "highrisk" patient groups, and definition of natural history and causes of treatment failure of these groups, is of major importance.…”

Increasing dose intensity of anthracycline antibiotics improves outcome in patients with acute myelogenous leukemia

“…In several trials, remission rates of 50-82% have been reported with the standard combination of daunorubicin, cytarabine with or without 6-thioguanine (DAT) [22][23][24]. Similarly, the substitution of 6-thioguanine for etoposide is synergistic in vitro and was effective in prolonging remission duration in younger patients [6].…”