Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Phase II trial of indicine N-oxide in relapsed acute leukemia of childhood. A report from the Childrens Cancer Study Group. 155 1

13-cis-Retinoic acid (13-cRA) induces maturation and differentiation of neoplastic myeloid cell lines in vitro. We conducted a phase I clinical trial of 13-cRA in patients with myelodysplastic syndromes (MDS), using a single daily oral dose schedule. Seventeen patients with MDS and one each with acute nonlymphoblastic leukemia and chronic myelogenous leukemia in blast crisis were treated with 13-cRA at doses ranging from 20 to 125 mg/m2/day. Hepatotoxicity was dose-limiting and was manifested by hyperbilirubinemia and increased SGOT levels. This effect was seen only at the highest dose level of 125 mg/m2/day and was completely reversible upon cessation of the drug. Other toxic effects were mild, and included cheilosis, hyperkeratosis, stomatitis, and elevation of serum triglyceride levels. Fifteen patients with MDS were evaluable for therapeutic response. Five patients showed improvement in hematologic parameters. These responses included normalization of bone marrow blast count and increases in leukocyte count, platelet count, and/or hemoglobin concentration. Responses were generally not seen until at least 3 weeks of therapy were completed. We conclude that further study of 13-cRA in myelodysplastic syndromes is warranted and recommend that future studies utilize a starting dose of 100 mg/m2.
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PMID:Phase I clinical trial of 13-cis-retinoic acid in myelodysplastic syndromes. 658 71