Multicentre phase III trial on fludarabine, cytarabine (Ara‐C), and idarubicin versus idarubicin, Ara‐C and etoposide for induction treatment of younger, newly diagnosed acute myeloid leukaemia patients

Abstract

Summary Fludarabine plus cytarabine (Ara‐C) and idarubicin (FLAI) is an effective and well‐tolerated induction regimen for the treatment of acute myeloid leukaemia (AML). This phase III trial compared the efficacy and toxicity of FLAI versus idarubicin plus Ara‐C and etoposide (ICE) in 112 newly diagnosed AML patients <60 years. Fifty‐seven patients received FLAI, as the first induction–remission course, and 55 patients received ICE. Post‐induction treatment consisted of high‐dose Ara‐C (HDAC). After HDAC, patients in complete remission (CR) received a second consolidation course (mitoxantrone, etoposide, Ara‐C) and autologous stem cell transplantation (auto‐SCT) or allogeneic (allo)‐SCT, according to the age, disease risk and donor availability. After a single induction course, CR rate was 74% in the FLAI arm and 51% in the ICE arm (P = 0·01), while death during induction was 2% and 9% respectively. Both haematological (P = 0·002) and non‐haematological (P = 0·0001) toxicities, especially gastrointestinal (i.e. nausea, vomiting, mucositis and diarrhoea), were significantly lower in FLAI arm. In both arms, relapses were more frequent in patients who were not submitted to allo‐SCT. After a median follow‐up of 17 months, 30% and 38% of the patients are in continuous CR in FLAI and ICE arm respectively. Our prospective randomised study confirmed the anti‐leukaemic effect and the low toxic profile of FLAI as induction treatment for newly diagnosed AML patients.

High feasibility and antileukemic efficacy of fludarabine, cytarabine, and idarubicin (FLAI) induction followed by risk‐oriented consolidation: A critical review of a 10‐year, single‐center experience in younger, non M3 AML patients

“…Some of these issues were prospectively evaluated by the recent randomized AML15 MRC trial in which investigators showed that FLAG-Ida achieved more CRs than daunorubicin 1 cytarabine (3 1 7) [23]. Similar conclusions, although on a smaller series of patients, had been drawn in an Italian randomized study comparing FLAG-Ida and Idarubicin, etoposide and Ara-C [36]. Furthermore, we recently retrospectively compared fludarabinecontaining and conventional induction regimens in NPM-mut AML patients and showed that FLAI-5, if compared to standard 3 1 7, resulted in significantly higher CR rates (86% vs. 69% with FLAI-5 and 3 1 7, respectively, P 0.021) and longer DFS at 24 months (P < 0.001) [37].…”

Clearance of leukaemic blasts from peripheral blood during standard induction treatment predicts the bone marrow response in acute myeloid leukaemia: a pilot study

“…This approach may make it possible to obtain, with a single course of treatment, a rate of CR comparable with that achieved using intensified induction for all patients (Bishop et al, 1996;Russo et al, 2005) but with a reduction in the overall toxicity. There are two potential advantages (a) no intensification for patients who do not need it; (b) patients The ranges of distribution of the ratios between baseline and daily absolute blast count, converted to a logarithmic scale (Log Reduction), have minimal overlap between CR and NCR groups.…”

Outcomes of allogeneic stem cell transplantation among patients with acute myeloid leukemia presenting active disease: Experience of a single European Comprehensive Cancer Center

“…16,17 In patients with relapsed AML, depending on cytogenetic profile, age and time of first remission, cytarabine-based salvage chemotherapy is sometimes satisfactory. 15,18,19 However, only a few randomized studies address this issue, which thus remains a gray area. 20,21 In second line setting, favorable, intermediate or high intermediate group are suitable to SWOG 9126 protocol (high dose cytarabine, daunorubicin and cyclosporine).…”