PHASE-II TRIAL OF INDICINE N-OXIDE IN RELAPSED ACUTE-LEUKEMIA OF CHILDHOOD - A REPORT FROM THE CHILDRENS-CANCER-STUDY-GROUP

We treated 31 children with acute lymphoblastic leukemia (ALL), 14 chi ldren with acute nonlymphoblastic leukemia (ANLL) in relapse, and 1 ch ild with chronic myelogenous leukemia (CML) in blast crisis (CALLA neg ative) with indicine N-oxide in a Phase II study. The efficacy and tox icity of the drug were assessed at two dose levels: 2,000 mg/m2/day fo r 5 consecutive days (14 patients) and 2,500 mg/m2/day for 5 consecuti ve days (17 patients). One patient with ALL at each dose level achieve d a complete response (CR) lasting 6 months and 1 month, respectively. The patient with CML achieved a partial response lasting 4 months. No ne of the patients with ANLL achieved a CR. Hepatotoxicity was mild (g rade 1 or 2) in 63% and moderate (grade 3) in 9% of patients; 3 patien ts (9%) experienced severe hepatotoxicity. Although indicine N-oxide h as some antileukemic activity in ALL and is safe at the doses used in this study, the antileukemic activity is significantly less at these t wo doses than at greater-than-or-equal-to 3,000 mg/m2/days for 5 conse cutive days. Unfortunately, when the higher doses are administered to children. they are associated with an unacceptably high incidence of s evere, irreversible hepatotoxicity.