MITOXANTRONE, ETOPOSIDE AND ARA-C VS DOXORUBICIN-DNA, ARA-C, THIOGUANINE, VINCRISTINE AND PREDNISOLONE IN THE TREATMENT OF PATIENTS WITH ACUTE MYELOCYTIC-LEUKEMIA - A RANDOMIZED COMPARISON

Complex-binding of anthracyclines to DNA may increase their therapeuti c efficacy. In a previous randomized trial patients with acute myelocy tic 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, etoposi de and ara-C (MEA) was found to have a high antileukaemic activity. In this randomized study of AML patients (15-60 years) induction treatme nt with MEA was compared to a combination of doxorubicin/DNA conjugate ara-C, thioguanine, vincristine and prednisolone (POCAL-DNA). The stu dy 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 mo nths for MEA and POCAL-DNA patients, respectively (p<0.03). In conclus ion, the MEA regimen has a very high antileukaemic activity in good ac cordance with our previous experience. Since we could not reproduce ou r earlier clinical results using DNA-bound anthracyclines, the source and preparation of DNA seem to be of major importance.