title: Mitoxantrone, etoposide and ara-C vs doxorubicin-DNA, ara-C, thioguanine, vincristine and prednisolone in the treatment of patients with acute myelocytic leukaemia. A randomized comparison.
abstract: Complex-binding of anthracyclines to DNA may increase their therapeutic efficacy. In a previous randomized trial patients with acute myelocytic leukaemia (AML) receiving combination chemotherapy including a DNA-bound doxorubicin preparation had a longer duration of first complete remission (CR) and survival than patients receiving free doxorubicin. In a parallel phase I/II study a combination of mitoxantrone, activity. In this randomized study of AML patients (15-60 years) induction treatment with MEA was compared to a combination of doxorubicin/DNA conjugate ara-C, thioguanine, vincristine and prednisolone (POCAL-DNA). The study was closed after an interim analysis of 86 patients. Thirty-five/42 (83%) and 20/44 (45%) patients entered CR in the MEA and POCAL-DNA groups, respectively (p < 0.001). With rescue therapy the corresponding figures were 88 and 64% (p < 0.02). Median survival was 27.8 and 13.1 months for MEA and POCAL-DNA patients, respectively (p < 0.03). In conclusion, the MEA regimen has a very high antileukaemic activity in good accordance with our previous experience. Since we could not reproduce our earlier clinical results using DNA-bound anthracyclines, the source and preparation of DNA seem to be of major importance.
authors.affiliation: Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Björkholm
authors.forename: J
authors.initials: J
authors.lastname: Liliemark
authors.forename: G
authors.initials: G
authors.lastname: Gahrton
authors.forename: G
authors.initials: G
authors.lastname: Grimfors
authors.forename: A
authors.initials: A
authors.lastname: Gruber
authors.forename: R
authors.initials: R
authors.lastname: Hast
authors.forename: G
authors.initials: G
authors.lastname: Juliusson
authors.forename: M
authors.initials: M
authors.lastname: Järnmark
authors.forename: A
authors.initials: A
authors.lastname: Killander
authors.forename: E
authors.initials: E
authors.lastname: Kimby
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D018736:DNA Adducts / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D011239:Prednisolone / Q000008:administration & dosage; D012008:Recurrence; D016019:Survival Analysis; D013866:Thioguanine / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D018736:DNA Adducts; C031902:doxorubicin-DNA; D003561:Cytarabine; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D011239:Prednisolone; D008942:Mitoxantrone; D013866:Thioguanine