Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia

Abstract

The purpose of this study was to determine the relative merits of idarubicin and daunorubicin in acute myeloid leukemia (AML) therapy. Thirty-two sites provided 214 previously untreated adults with AML aged 15 years or more who were randomized to receive for induction therapy cytarabine 100 mg/m2/d as a continuous 7-day infusion plus either daunorubicin 45 mg/m2/d (A + D) or idarubicin 13 mg/m2/d (A + I), daily on the first three days of treatment. Postremission therapy consisted of two courses of the induction regimen at the same daily doses, with the anthracycline administered for 2 days and cytarabine for 5. The complete response (CR) rates for evaluable patients were 70% (A + I) and 59% (A + D) (P = .08). The difference in CR rates was significant in patients aged 18 to 50 years (88% for A + I, 70% for A + D, P = .035). Resistant disease was a significantly more frequent cause of induction therapy failure with A + D than with A + I. Hyperleukocytosis (white blood cell count greater than 50,000/microL) unfavorably affected the attainment of CR with A + D but not with A + I. CR duration was significantly greater after A + I. CR duration was significantly greater after A + I treatment, and the survival of all randomized patients treated with A + I was significantly better than that observed after A + D treatment (median 12.9 months v 8.7 months, respectively, P = .038). Toxicity of the two treatments was similar, although A + I patients experienced more prolonged myelosuppression during consolidation therapy, and a greater incidence of mild chemical hepatitis was observed in the A + I group. It is concluded that, at the doses and schedule used in this study, A + I is superior to A + D for induction therapy of AML in adults.

Incidence of bacterial and fungal infections in newly diagnosed acute myeloid leukaemia patients younger than 65 yr treated with induction regimens including fludarabine: retrospective analysis of 224 cases

“…Addition of a third drug to the standard combination of anthracycline and arabinosyl cytosine (Ara-C) or the use of high-dose Ara-C (HD-AC) are the most common approaches to intensify induction (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). We attempted to improve induction's efficacy with a non-conventional induction regimen of fludarabine in combination with intermediate-dose Ara-C and standard dose idarubicin (FLAI) (23)(24)(25)(26)(27).…”

Conventional and high‐dose daunorubicin and idarubicin in acute myeloid leukaemia remission induction treatment: a mixed treatment comparison meta‐analysis of 7258 patients

“…Methodological quality of included studies was rather low. None of the studies described blinding of patients, outcomes assessors, caregivers or statisticians [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]. Only two trials described allocation concealment of treatments [26,28].…”

“…Only two trials described allocation concealment of treatments [26,28]. Moreover, only seven studies followed an intention-to-treat analysis [22,24,26,28,29,33,34]. Details on methodological quality assessment and risk of bias can be found in Table 3.…”

“…A similar result could be observed for HDD confronted with CDD (RR 1.13, 95% CrI 1.02-1.26). However, no difference was observed when IDA and HDD were compared against each other (RR 1.00, 95% CrI [18,[20][21][22][23][24][25][28][29][30][32][33][34], when considering only those patients that attained FC-CR (given that all studies allowed reinduction at least once for patients showing resistant disease after the first cycle before considering it as induction failure) it was shown that both IDA (RR 1.37, 95% CrI 1.22-1.54) and HDD (RR 1.32, 95% CrI 1.18-1.50) demonstrated higher FC-CR rates than CDD. Again, HDD and IDA showed no significant differences in FC-CR rates (RR 0.97, 95% CrI 0.86-1.10) when compared with each other.…”

High‐dose idarubicin and busulphan as conditioning to autologous stem cell transplantation in adult patients with acute myeloid leukaemia

“…Different approaches, including in vivo or ex vivo purging, immunotherapy after ASCT and intensification of conditioning regimen have been investigated in an attempt to reduce recurrence of AML in patients undergoing ASCT (Gorin, 2002;Linker, 2003;Stein et al, 2003;Nathan et al, 2004 ). In particular, preliminary data suggest that the addition of IDA, an intercalating agent with powerful antileukaemic activity (Vogler et al, 1992;Wiernik et al, 1992;Reiffers et al, 1996), may result in a consistent reduction of relapse rate either in autologous or in allo-SCT (Schaap et al, 1997;Jerjis et al, 1998;Lawson et al, 1999;Mengarelli et al, 2000). Furthermore, encouraging results have been recently reported with the adoption of an intensified preparative regimen of Bu 16 mg/kg p.o.…”