Daunorubicin continuous infusion induces more toxicity than bolus infusionin acute lymphoblastic leukemia induction regimen: a randomized study

We report the first randomized study assessing the efficacy and safety of d aunorubicin (DNR) continuous infusion (CI) compared to the more conventiona l 30 min infusion (i.v.) in newly diagnosed adult acute lymphoblastic leuke mia (ALL). Seventy-seven patients were initially randomized to receive eith er a 24h CI DNR (60 mg/m(2) days 2-4) (40 patients) or bolus DNR at the sam e dosage (37 patients) with vincristine (2 mg i.v. days 1, 8, 15) and oral prednisone (60 mg/m(2) days 1-15), without hematopoietic growth factor supp ort, as an induction regimen. The distribution of adverse prognostic factor s was comparable in the two-induction arm. Acute toxicity was more importan t in the CI arm. Gram negative infection (9 vs 1 gram negative septicemia, P = 0.01) and infection-related deaths (6 vs 1 deaths, P = NS) occurred mor e frequently in the CI arm during the induction treatment than in the i.v. arm, leading to the study interruption. Neutropenia but not thrombopenia du ration was significantly longer in the CI arm than in the i.v. arm (18 days vs 14 days, P > 0.05 and 16 days vs 12 days, P > 0.05, respectively). Desp ite a similar CR rate according to the method of DNR administration (68% in the CI DNR arm vs 76% in the i.v. arm after the first course), there was a trend toward higher freedom from relapse (FFR) after DNR CI (48% vs 28% in the i.v. arm at 5 years, P = NS), suggesting that despite this high toxici ty, DNR CI may improve the CR quality and decrease further the residual dis ease.