title: Phase II trial of indicine N-oxide in relapsed acute leukemia of childhood. A report from the Childrens Cancer Study Group.
abstract: We treated 31 children with acute lymphoblastic leukemia (ALL), 14 children with acute nonlymphoblastic leukemia (ANLL) in relapse, and 1 child with chronic myelogenous leukemia (CML) in blast crisis (CALLA negative) with indicine N-oxide in a Phase II study. The efficacy and toxicity of the drug were assessed at two dose levels: 2,000 mg/m2/day for 5 consecutive days (14 patients) and 2,500 mg/m2/day for 5 consecutive days (17 patients). One patient with ALL at each dose level achieved a complete response (CR) lasting 6 months and 1 month, respectively. The patient with CML achieved a partial response lasting 4 months. None of the patients with ANLL achieved a CR. Hepatotoxicity was mild (grade 1 or 2) in 63% and moderate (grade 3) in 9% of mild (grade 1 or 2) in 63% and moderate (grade 3) in 9% of patients; 3 patients (9%) experienced severe hepatotoxicity. Although indicine N-oxide has some antileukemic activity in ALL and is safe at the doses used in this study, the antileukemic activity is significantly less at these two doses than at greater than or equal to 3,000 mg/m2/days for 5 consecutive days. Unfortunately, when the higher doses are administered to children, they are associated with an unacceptably high incidence of severe, irreversible hepatotoxicity.
authors.affiliation: Department of Pediatrics, Mayo Clinic Foundation, Rochester, Minnesota.
authors.forename: J S
authors.initials: JS
authors.lastname: Miser
authors.forename: W A
authors.initials: WA
authors.lastname: Smithson
authors.forename: W
authors.initials: W
authors.lastname: Krivit
authors.forename: C H
authors.initials: CH
authors.lastname: Hughes
authors.forename: D
authors.initials: D
authors.lastname: Davis
authors.forename: M D
authors.initials: MD
authors.lastname: Krailo
authors.forename: G D
authors.initials: GD
authors.lastname: Hammond
mesh_terms: D000208:Acute Disease; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D004341:Drug Evaluation; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D011763:Pyrrolizidine Alkaloids / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011763:Pyrrolizidine Alkaloids; C013095:indicine-N-oxide