title: A Randomized Comparison of Doxorubicin and Doxorubicin-DNA in the Treatment of Acute NonLymphoblastic Leukemia.
abstract: In the light of previous findings that treatment of leukemia patients with DNA-linked doxorubicin gave higher doxorubicin concentrations in leukemic cells than treatment with doxorubicin alone, the Leukemia Group of Middle Sweden performed a randomized clinical trial to compare the effects of doxorubicin and doxorubicin-DNA in patients with acute non-lymphoblastic leukemia. One hundred and twenty consecutive patients within the age range 15 to 60 years were randomized to one of three treatment groups. In two of these, remission induction treatment was performed with prednisolone, vincristine, ara-C and thioguanine combined with either doxorubicin or doxorubicin-DNA. Patients entering a complete remission received intensive consolidation during 16 months with 4 courses each of doxorubicin (+/ - DNA)/ara-C, doxorubicin (+/ - DNA)/azacytidine, ara-C and amsacrine. The third treatment group followed a protocol from a previous study with daunorubicin and ara-C for induction therapy and a less intensive maintenance therapy. No further patients were assigned to this "control" group after 3 years or to the two other groups after 6 years. This report is based on a follow-up 31 months thereafter. The overall rate of complete remission was 67% and the mean time to complete remission was 71 days, with no differences between the treatment groups. Patients treated with the doxorubicin-DNA conjugate had a significantly longer survival [median for all patients 27.2 months (p < 0.01) and for patients in CR 47.0 months (p < 0.025)] and longer duration of first remission (median 23.6 months, p < 0.025) than the other groups. There were significantly fewer reports of cardiotoxicity (p < 0.05) and severe intestinal toxicity (p < 0.02) in patients treated with the doxorubicin-DNA conjugate and there was a tendency towards less hepatic (p < 0.08) and renal toxicity (p < 0.08). The frequency of myelosuppression, fever and infectious complications was similar in all three groups. Complex binding to DNA appears to increase the therapeutic effects and reduce some toxic effects of doxorubicin in patients with ANLL.
authors.affiliation: a Department of Medicine, Huddinge Hospital, Huddinge, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Paul
authors.affiliation: a Department of Medicine, Huddinge Hospital, Huddinge, Sweden.
authors.forename: U
authors.initials: U
authors.lastname: Tidefelt
authors.affiliation: a Department of Medicine, Huddinge Hospital, Huddinge, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Gahrton
authors.affiliation: b Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Björkholm
authors.affiliation: c Department of Medicine, Medical Centre Hospital örebro, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Järnmark
authors.affiliation: d Department of Medicine, University Hospital, Uppsala, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Killander
authors.affiliation: e Department of Medicine, Danderyds Hospital, Danderyd, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Kimby
authors.affiliation: a Department of Medicine, Huddinge Hospital, Huddinge, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Liliemark
authors.affiliation: a Department of Medicine, Huddinge Hospital, Huddinge, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Lindeberg
authors.affiliation: a Department of Medicine, Huddinge Hospital, Huddinge, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Lindquist
authors.affiliation: a Department of Medicine, Huddinge Hospital, Huddinge, Sweden.
authors.forename: D
authors.initials: D
authors.lastname: Lockner
authors.affiliation: a Department of Medicine, Huddinge Hospital, Huddinge, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Lönnqvist
authors.affiliation: f Department of Medicine, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Mellstedt
authors.affiliation: e Department of Medicine, Danderyds Hospital, Danderyd, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Merk
authors.affiliation: g Department of Medicine, Södersjukhuset, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Palmblad
authors.affiliation: h Department of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Peterson
authors.affiliation: d Department of Medicine, University Hospital, Uppsala, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Simonsson
authors.affiliation: c Department of Medicine, Medical Centre Hospital örebro, Sweden.
authors.forename: A M
authors.initials: AM
authors.lastname: Stalfelt
authors.affiliation: i Department of Pathology, University Hospital, Uppsala, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Sundström
authors.affiliation: c Department of Medicine, Medical Centre Hospital örebro, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Wadman
authors.affiliation: f Department of Medicine, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Wedelin
authors.affiliation: g Department of Medicine, Södersjukhuset, Stockholm, Sweden.
authors.forename: A M
authors.initials: AM
authors.lastname: Udén
authors.affiliation: d Department of Medicine, University Hospital, Uppsala, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Öberg
authors.affiliation: j Department of Pathology, Karolinska Hospital, Stockholm, Sweden.
authors.forename: Å
authors.initials: Å
authors.lastname: Öst
keywords: Clinical trial; DNA conjugate; Doxorubicin; Leukemia; Random allocation; acute; nonlymphocytic