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

Publisher Website
Google Scholar
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, etoposide and ara‐C (MEA) was found to have a high antileukaemic 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.