Doxorubicin or daunorubicin given upfront in a therapeutic window are equally effective in children with newly diagnosed acute lymphoblastic leukemia. A randomized comparison in trial CoALL 07-03.

Background: The anthracyclines daunorubicin (DNR) and doxorubicin (DOX) are among the most important drugs in the treatment of childhood acute lymphoblastic leukemia, however there are conflicting in vitro data about the comparative efficacy and equivalent doses of both anthracyclines. To address the question of in vivo efficacy of both anthracyclines, patients enrolled in the CoALL 07-03 trial were randomized to receive one single dose of either doxorubicin 30 mg/m(2) , daunorubicin 30 mg/m(2) , or daunorubicin 40 mg/m(2) upfront induction therapy.

Procedure: Children with newly diagnosed B-Precursor ALL or T-ALL were eligible for the randomized comparison. From the percentage of blasts and the white blood cell count (WBC) the absolute number of leukemic cells per µl peripheral blood (PB) was calculated and the initial value before DOX/DNR infusion equated as 100%. Main target criterion of this study was the leukemic cell decrease from Day 0 to Day 7.

Results: Seven hundred forty three patients were randomized: 247 to the DOX; 252 to the DNR 30 mg/m(2) ; and DNR to the 40 mg/m(2) arm. The in vivo response was similar in all three treatment arms with a comparable blast decline in the peripheral blood. The percentages of patients with a clear non-response (M3 marrow) and moreover, the level of minimal residual disease (MRD) on Day 15 or at the end of induction were similar.

Conclusion: In vivo efficacy of a single dose daunorubicin 30 or 40 mg/m(2) is similar to that of doxorubicin given in a dose of 30 mg/m(2) .