Treatment of newly diagnosed AML, RAEB-t or RAEB with lisofylline or placebo in addition to chemotherapy

To determine whether the addition of lisofylline (LSF) to idarubicin (12 mg /m(2) daily x 3) + ara-C (1.5 g/m(2) daily x 4) affects the rates of infect ion, serious infection, CR or mortality during remission induction of newly diagnosed AML, RAEB-t or RAEB, we randomized 70 patients to 3 mg/kg lisofy lline or placebo every 6 h i.v., to begin 6 h before the first dose of idar ubicin and to continue until recovery of neutrophil and platelet counts or for 28 days, whichever came first. Eligibility required that patients be be low age 71 years, have no history of abnormal counts, or chemotherapy for a prior malignancy, and have a creatinine <1.6 mg/dl and bilirubin <3.0 mg/d l. The study was double-blinded and infections were tabulated separately an d independently at MD Anderson and by a three-member outside panel of exper ts. Logistic regression was used to assess the relative effects of treatmen t arm (LSF or placebo), age, performance status, treatment site (laminar ai r flow room or not), and cytogenetics on rates of infection and serious inf ection following the first course of chemotherapy, and on CR rate. There we re 84% and 87% concordance between the expert panel and MD Anderson enumera tions of infection and serious infections, respectively. Both analyses foun d no significant (P < 0.05) differences between the rates of infection, or serious infection, in the placebo and LSF groups. CR, 60-day, and overall m ortality rates were similar in the two groups, as were time to neutrophil a nd blood count recovery and outcome once in CR. Logistic regression analyse s supported the above conclusions. Severe nausea/vomiting and mucositis wer e more frequent in the LSF group. Our results suggest that larger studies o f LSF in newly diagnosed AML, RAEB-t, or RAEB are not warranted.