title: Itraconazole prophylaxis in pediatric cancer patients receiving conventional chemotherapy or autologous stem cell transplants.
abstract: OBJECTIVE
  During the renovation works at our institution, the incidence density for invasive aspergillosis (IA) increased from <0.5 to 0.99/1,000 inpatient days in 2001. As a direct response to this increased environmental risk, itraconazole (ITC) was administered for primary prophylaxis in pediatric cancer patients for whom a particular high risk of IA was anticipated due to prolonged severe neutropenia (>10 days), autologous stem cell transplantation, acute myeloblastic leukemia or relapsed acute lymphoblastic leukemia, or high-dose steroids >3 weeks.
  
  
  METHODS
  In this open-label, prospective observational study, ITC was given in ITC solution or capsule. Trough concentrations were measured in plasma with high-performance liquid chromatography after at least 7 days of treatment. Doses were adjusted to target plasma trough ITC concentrations > or =0.5 mg/l.
  
  
  RESULTS
  From 2001 to 2005, 39 pediatric cancer patients received 44 prophylactic ITC cycles; 102 trough plasma concentrations were measured after oral administration. Plasma target concentrations >0.5 mg/l were achieved with both formulations. A median dose of 8 mg kg(-1) day(-1) (3.5-16.0 mg kg(-1) day(-1)) was necessary in pediatric oncology patients. The bioavailability of the liquid formulation was significantly lower when the solution was given by a feeding tube. Adverse effects (gastrointestinal, elevated transaminases, and one hemolysis) which led to the cessation of the ITC prophylaxis were reported in 11% of all courses. No breakthrough infection was seen in this pediatric population.
  
  
  CONCLUSIONS
  Oral ITC offers a feasible and inexpensive option for antifungal prophylaxis in selected pediatric cancer patients. Drug monitoring and meticulous consideration of possible interactions and adverse effects are mandatory.
authors.affiliation: Department of Pediatric Hematology/Oncology, Children's Hospital, Medical Center University of Bonn, Adenauerallee 119, 53113, Bonn, Germany. asimon@ukb.uni-bonn.de
authors.forename: Arne
authors.initials: A
authors.lastname: Simon
authors.forename: Mette
authors.initials: M
authors.lastname: Besuden
authors.forename: Sandra
authors.initials: S
authors.lastname: Vezmar
authors.forename: Carola
authors.initials: C
authors.lastname: Hasan
authors.forename: Dagmar
authors.initials: D
authors.lastname: Lampe
authors.forename: Sigrid
authors.initials: S
authors.lastname: Kreutzberg
authors.forename: Axel
authors.initials: A
authors.lastname: Glasmacher
authors.forename: Udo
authors.initials: U
authors.lastname: Bode
authors.forename: Gudrun
authors.initials: G
authors.lastname: Fleischhack
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects; D001228:Aspergillosis / Q000209:etiology / Q000517:prevention & control*; D001230:Aspergillus / Q000187:drug effects; D018890:Chemoprevention; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007223:Infant; D017964:Itraconazole / Q000008:administration & dosage* / Q000627:therapeutic use; D007938:Leukemia / Q000628:therapy; D008223:Lymphoma / Q000628:therapy; D008297:Male; D009369:Neoplasms / Q000150:complications / Q000628:therapy*; D009447:Neuroblastoma / Q000628:therapy; D009503:Neutropenia / Q000150:complications; D011446:Prospective Studies; D033581:Stem Cell Transplantation / Q000009:adverse effects
chemical_list: D000935:Antifungal Agents; D000970:Antineoplastic Agents; D017964:Itraconazole