A randomized comparison of maintenance treatment with androgens, immunotherapy, and chemotherapy in adult acute myelogenous leukemia: A leukemia-lymphoma group trial of the EORTC

Abstract

Twenty-three European centers participated in a randomized clinical trial (AML-5) to study the effect of androgens and immunotherapy during maintenance in adult acute myelogenous leukemia. Induction treatment consisted of Adriamycin (doxorubicin) 50 mg/m2 day 1, vincristine VCR 1 mg/m2 day 2, and cytosine arabinoside 80 mg/m2 every 12 hours by push injection days 3-9. Patients in complete remission were randomized into four groups: (1) 6-mercaptopurine 70 mg/m2 days 1-14, methotrexate 15 mg/m2 twice weekly days 15-28, and reinduction with daunorubicin 35 mg/m2 and vincristine 1 mg/m2 day 29; (2) chemotherapy as in group 1 plus stanozolol 0.15 mg/kg/day; (3) 6-thioguanine 70 mg/m2 orally on 4 consecutive days and cytosine arabinoside 80 mg/m2 subcutaneously day 5 every week; and (4) chemo-therapy as in Group 3 plus irradiated blast cells treated with neuraminidase. Three hundred forty-eight patients were eligible and 295 were evaluable. The median age was 45 yrs. A complete remission was achieved in 64% of the patients, with 158 complete remissions randomized. Patients not randomized and patients receiving bone marrow transplantation (BMT) were analyzed separately. There was no difference in disease-free survival (DFS) or survival in the four maintenance arms. For patients reaching complete remission, the median DFS was 40 weeks, and median survival was 22 months with 30% surviving a t 4 years. The overall survival was 18% at 4 years. There was no beneficial effect for DFS or survival by adding either immunotherapy or androgens to chemotherapy during maintenance. However, patients receiving immunotherapy seemed to have a higher rate of responses to reinduction after relapse than those in the other treatment arms. Cancer W617-623, 1986. URING THE LAST DECADE, major progress has been D made in the management of acute myelogenous leukemia (AML). Many recent studies report complete

ACUTE MYELOID LEUKEMIA: TREATMENT OVER 60

“…The age‐related study results are listed in Table 1 in the order of increasing age in the groups of patients treated (16–27, 30–40, 43–48). If age specific therapeutic results were reported, the related publications were listed for separate age groups.…”

“…While Table 1 provides a synopsis of different treatment modalities, differences between the trials must be interpreted with caution. As children were included in some trials (17, 18, 20, 33, 34, 36) or various proportions of patients became excluded at the occasion of randomization in remission (17, 19, 21, 23, 35, 36, 38, 45, 47, 48) fair interstudy comparisons are certainly compromized by unknown selection factors.…”

Addition of Androgens Improves Survival in Elderly Patients With Acute Myeloid Leukemia: A GOELAMS Study

“…Androgens have been demonstrated to be useful in treating aplastic anemia since the late 1970s, [12][13][14][15] which led to testing these drugs in the treatment of AML with some success [16][17][18] in the 1980s. Most of these studies, however, were monocentric or had insufficient statistical power because of a low number of enrolled patients.…”

Combining the past and present to advance immuno-radiotherapy of cancer

“…A marginally significant better relapse-free survival was noted. In an EORTC randomized trial, no significant beneficial effect on disease-free survival was noted for the group of AML patients who received immunotherapy with irradiated blasts, although these patients seemed to have higher response rates to re-induction of chemotherapy after relapse [84]. In a randomized study, on 64 patients with myelogenous leukemia who entered complete remission with chemotherapy, the administration of neuraminidase-treated allogenic blasts improved the median relapse-free survival from 15 to 40 months [85].…”