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

Abstract

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.

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

“…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).…”

“…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).…”

A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group

“…[1][2][3][4][5] For patients younger than 55 to 60 years, multiple prospective randomized studies compared daunorubicin at a dose of 45 mg/m 2 with idarubicin, amsacrine, aclacinomycin A, and mitoxantrone, while keeping the dose of cytarabine constant. [6][7][8][9][10][11][12][13][14] Virtually all of these agents were at least as effective as, if not better than, daunorubicin at a dose of 45 mg/m 2 . However, the results for patients older than 55 to 60 years are equivocal and do not confirm the superiority of any anthracycline when compared with 45 mg/m 2 daunorubicin.…”

Acute Myeloid Leukaemia

“…[119–121] Unfortunately, information about novel agents is minimal. Candelaria et al [110] reported preliminary results using hydralazine and valproic acid as an epigenetic modifier in ten patients with refractory cytopenias with MLD in Mexico.…”