Treatment of acute myelogenous leukaemia in patients aged 50–65: idarubicin is more effective than zorubicin for remission induction and prolonged disease‐free survival can be obtained using a unique consolidation course

Abstract

From December 1987 to June 1992, 251 patients aged 50-65 with de novo acute myelogenous leukaemia (AML) were recruited to a multi-institutional randomized clinical trial. Induction therapy consisted of Ara-C (200 mg/ m2, continuous infusion, days 1-7) with either zorubicin (ZRB) (200 mg/m2, i.v., days 1-4) or idarubicin (IDR) (8 mg/ m2, i.v., days 1-5). Consolidation therapy consisted of a single course of intensive chemotherapy with high-dose Ara-C (3 g/m2, 3 h infusion, q 12 h, days 1-4) and m-Amsa (100 mg/m2/d, i.v., days 5-7). The complete remission (CR) rate was (73%) with Ara-C/ IDR versus (60%) with Ara-C/ZRB (P = 0.033). In multivariate analysis, factors found to be significant in predicting CR were normal karyotype and treatment with IDR. With a median follow-up of 73 months, the median disease-free survival (DFS) duration of all CR patients and the probability of CR at 6 years were 17 months and 29%. In multivariate analysis the only factor associated with an increased DFS duration was a normal karyotype. The median event-free survival (EFS) duration for all evaluable patients and the median overall survival duration for all eligible patients were respectively 7 and 12 months without any difference between induction arms. The study shows that in patients aged 50-65 idarabicin is more effective than zorubicin for remission induction. However, the type of anthracycline did not influence overall survival duration. Using a unique consolidation course, we observed a prolonged DFS which compares favourably with results obtained with more prolonged consolidation therapy or maintenance treatment.

Anthracyclines during induction therapy in acute myeloid leukaemia: a systematic review and meta‐analysis

“…DNR versus IDA was reported in eight trials (Eridani et al, 1989;Berman et al, 1991;Vogler et al, 1992;Wiernik et al, 1992;Masaoka et al, 1996;Creutzig et al, 2001;Mandelli et al, 2009;Ohtake et al, 2011), DNR versus MTZ in 6 trials (Arlin et al, 1990;Wahlin et al, 1991;Pavlovsky et al, 1994;Nikanfar et al, 2007;Mandelli et al, 2009;Burnett et al, 2010), IDA versus MTZ in 3 trials (Beksac et al, 1998;De Moerloose et al (2011), Mandelli et al, 2009) and DNR versus ACR was reported in two trials (Nagura et al, 1994;de Nully Brown et al, 1997). Another 10 anthracycline comparisons were evaluated in single studies as outlined in Table I (Paul et al, 1981(Paul et al, , 1991Yates et al, 1982;Morrison et al, 1992;Harousseau et al, 1996;Pignon et al, 1996;Takemoto & Ogawa, 1998;Intragumtornchai et al, 1999;Creutzig et al, 2010). High-dose versus standard-dose DNR was investigated in three studies (Yates et al, 1982;Fernandez et al, 2009;Lee et al, 2011) and one study compared continuous administration with bolus administration of MTZ (Koc et al, 2004).…”

Idarubicin to intensify the conditioning regimens of autologous bone marrow transplantation for patients with acute myeloid leukemia in first complete remission

“…29,30 Idarubicin also induced a higher complete remisson rate 4,29,31,32 in older patients. 33 Maintenance of complete remission after remission-induction therapy for AML can be achieved by intensive consolidation therapy followed by allogeneic or autologous stem cell transplantation or by chemotherapy.…”

“…Keywords: idarubicin; conditioning regimens; autologous bone marrow transplantation; acute myeloid leukemia; first complete remission A complete remission (CR) rate of 70-80% can be achieved in patients with newly diagnosed acute myeloid leukemia (AML) by currently used remission-induction regimens. Addition of a third drug such as etoposide, 1,2 replacement of daunorubicin by new anthracyclines such as idarubicin, [3][4][5] Correspondence: Dr Sh Jerjis, Division of Hematology, University Hospital St Radboud, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands Received 24 October 1997; accepted 14 February 1998 and high-dose cytarabine (HiDAC) 6,7 have improved the remission percentage of conventional regimens based on 3 days of daunorubicin and 10 days of standard-dose cytarabine. 8 Without further treatment almost all patients are expected to relapse.…”

Older adults with acute myeloid leukemia

“…In the past decade, several randomized trials purported to show that idarubicin was superior to the standard daunorubicin [37][38][39][40][41]. One of these trials was limited to older adults [41].…”