Mitoxantrone and cytarabine versus daunorubicin and cytarabine in previously untreated patients with acute myeloid leukemia

Wåhlin, Anders; Hörnsten, Per; Hedenus, Michael; Malm, Claes

doi:10.1007/bf00685827

Cited by 20 publications

(9 citation statements)

References 13 publications

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“…Characteristics of included studies are presented in Table I. 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).…”

Section: Resultsmentioning

confidence: 99%

“…An advantage in long-term survival was only observed in one study (Berman et al, 1997). The anthraquinone derivate mitoxantrone (MTZ) has also been extensively used with cytarabine as part of effective induction regimens (Arlin et al, 1990;Wahlin et al, 1991;Pavlovsky et al, 1994). Several other anthracyclines, such as doxorubicin, aclarubicin (ACR), or rubidazone, have also been tested in AML induction therapy strategies, either as part of RCTs or in single arm studies (Yates et al, 1982;Morrison et al, 1992;Nagura et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2013

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SummaryThis systematic review and meta-analysis compared the efficacy of different anthracyclines and anthracycline dosing schedules for induction therapy in acute myeloid leukaemia in children and adults younger than 60 years of age. Twenty-nine randomized controlled trials were eligible for inclusion in the review. Idarubicin (IDA), in comparison to daunorubicin (DNR), reduced remission failure rates (risk ratio (RR) 0Á81; 95% confidence interval (CI), 0Á66-0Á99; P = 0Á04), but did not alter rates of early death or overall mortality. Superiority of IDA for remission induction was limited to studies with a DNR/IDA dose ratio <5 (ratio <5: RR 0Á65; 95% CI, 0Á51-0Á81; P < 0Á001; ratio ! 5: RR 1Á03; 95% CI, 0Á91-1Á16; P = 0Á63). Higher-dose DNR, compared to lower-dose DNR, was associated with reduced rates for remission failure (RR 0Á75; 95% CI, 0Á60-0Á94; P = 0Á003) and overall mortality (RR 0Á83; 95% CI, 0Á75-0Á93; P < 0Á001), but not for early death. Comparisons of several other anthracycline derivates did not reveal significant differences in outcomes. Survival estimates in adults suggest that both high-dose DNR (90 mg/m 2 daily 9 3 or 50 mg/ m 2 daily 9 5) and IDA (12 mg/m 2 daily 9 3) can achieve 5-year survival rates of between 40 and 50 percent.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2013

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“…In 44 patients in Sweden allocated to the same treatment arms, Wahlin et al [14] obtained similar rates of complete remission and survival with MTT+Ara-C and DNM + Ara-C.…”

Section: Discussionmentioning

confidence: 71%

A randomized study of mitoxantrone plus cytarabine versus daunomycin plus cytarabine in the treatment of previously untreated adult patients with acute nonlymphocytic leukemia

et al. 1994

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Between May 1985 and November 1988, 143 adult patients with previously untreated acute nonlymphocytic leukemia were randomized to receive mitoxantrone and cytarabine (MTT+Ara-C) or daunomycin and cytarabine (DNM+Ara-C) in order to compare the efficacy and acute and chronic toxicities. Therapy consisted of 3 days of MTT 12 mg/m2/i.v. or DNM 45 mg/m2/i.v.; both groups received Ara-C 100 mg/m2 daily by continuous infusion (CI) for 7 days. Those who failed to achieve a complete remission after one induction course received a second induction course for 2 and 5 days at the same doses. All the patients who achieved complete remission received two consolidations of 2 days of MTT or DNM and 5 days of Ara-C in CI at the same dose as for induction. Of the 72 patients on MTT+Ara-C, 38 (53%) achieved complete remission, compared with 29 (43%) of 67 treated with DNM+Ara-C. Three and 5 patients had partial remission, 7 and 18 failed to respond, 24 and 15 died in the first 21 days of induction, of those treated with MTT+Ara-C or DNM+Ara-C, respectively (p = 0.34). Median duration of complete remission and survival was 185 and 103 days or 165 and 160 days, respectively (p = 0.85). More early deaths were observed with MTT+Ara-C due to greater myelosuppression, and a higher incidence of failure with DNM+Ara-C. No significant differences between treatment groups were observed in 21 categories of adverse events. The results demonstrate similar incidence of complete response, length of duration of complete remission, overall survival, and toxicity with MTT+Ara-C and DNM+Ara-C.

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“…[120][121][122] The incidence of cardiotoxicity with mitoxantrone appears to be associated with the total dose received)120] It is currently estimated that patients who receive a cumulative dose of 140 mg/m 2 have a cumulative 2.6% probability of developing clinical CHF, and that the overall cumulative probability of moderate to severe decreases in left ventricular ejection fraction at this dose is 13%)123] Age greater than 70 years has also been implicated in the development of CHF with mitoxantrone in patients with breast cancer'! No cardiotoxicity was attributed to mitoxantrone in a further comparison with daunorubicin in 41 patients (table 11») 76] Myocardial infarctions were reported in 2 patients (both of whom had pre-existing coronary disease) and moderate cardiotoxicity was documented in 2 of 104 patients aged over 60 years who received mitoxantrone with cytarabine.l 69 ] [1I9] In the randomised multicentre US study described in section 3.1.1 and table 11, [73] 8 patients in each treatment group (mitoxantrone with cytarabine or daunorubicin with cytarabine) developed CHF.…”

Section: Cardiotoxicitymentioning

confidence: 92%

Mitoxantrone

Dunn¹,

Goa²

1996

Drugs & Aging

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Acute nonlymphoblastic leukaemia (ANLL) is a malignant condition strongly associated with advancing age. Of adult acute leukaemias, 80 to 85% are classified as ANLL, with more than half of all patients being aged over 60 years. Although advancing age has been reported to be a poor prognostic factor in ANLL, recent clinical trials have shown good results in patients aged 60 years and over after coadministration of the anthracenedione antineoplastic agent mitoxantrone with cytarabine. In 1 study in particular, which involved patients aged 60 to 81 years, no correlation was found between increasing age and response rate. However results of a major clinical trial showed age greater than 60 years to be associated with poorer outcomes. Mitoxantrone as initial induction treatment is at least as effective as daunorubicin when either drug is given in combination with cytarabine to patients with previously untreated ANLL. Complete response rates in randomised comparative trials were 53 to 67% after mitoxantrone with cytarabine and 37 to 70% after daunorubicin with cytarabine. In a major US study, significantly more patients achieved a complete response after 1 treatment cycle of mitoxantrone and cytarabine than after daunorubicin and cytarabine. Mitoxantrone has also been effective in inducing complete remissions in patients with relapsed or refractory ANLL, mainly in combination with other antineoplastic agents. Overall survival appears similar after treatment with regimens containing either mitoxantrone or daunorubicin in patients with ANLL, although there have been reports of trends towards increased survival rates with mitoxantrone. The incidence of cardiotoxicity appears low in patients with ANLL who have received mitoxantrone. Lower cardiotoxicity of mitoxantrone relative to daunorubicin has not been conclusively demonstrated in patients with ANLL, although trials in patients with breast cancer have shown mitoxantrone to cause fewer cardiac adverse effects than doxorubicin. This is of particular interest in the elderly, as this group of patients is especially susceptible to the effects of anthracycline-induced cardiac toxicity. Thus, mitoxantrone is a suitable first-line agent for the induction of remission in patients with ANLL, with clearly demonstrated efficacy in patients aged 60 years and over.

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Mitoxantrone and cytarabine versus daunorubicin and cytarabine in previously untreated patients with acute myeloid leukemia

Cited by 20 publications

References 13 publications

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

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

A randomized study of mitoxantrone plus cytarabine versus daunomycin plus cytarabine in the treatment of previously untreated adult patients with acute nonlymphocytic leukemia

Mitoxantrone

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