title: Phase I study of ICRF-187 in pediatric cancer patients and comparison of its pharmacokinetics in children and adults.
abstract: A phase I study of ICRF-187 as a 2-hour iv infusion daily for 3 days was conducted in 46 evaluable pediatric patients. The maximum tolerated dose was 3500 mg/m2/day X 3 based on changes in hepatic function and coagulation abnormalities encountered when larger dosages were administered. One patient with acute lymphocytic leukemia achieved a complete remission and four cleared the blood of lymphoblasts. No other objective responses were seen. Pharmacokinetic analysis showed that the children had a larger volume of distribution per kilogram of body weight in the central compartment and total body and a more rapid total-body clearance than adults. These parameters can explain only part of the increased tolerance of children to ICRF-187.
mesh_terms: D000293:Adolescent; D000328:Adult; D001780:Blood Coagulation Tests; D056486:Chemical and Drug Induced Liver Injury; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D004798:Enzymes / Q000097:blood; D006207:Half-Life; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007700:Kinetics; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010879:Piperazines / Q000627:therapeutic use*; D011929:Razoxane / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D013237:Stereoisomerism; D014018:Tissue Distribution
chemical_list: D004798:Enzymes; D010879:Piperazines; D011929:Razoxane