Itraconazole prophylaxis in pediatric cancer patients receiving conventional chemotherapy or autologous stem cell transplants.
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.
Simon
Arne
A
Department of Pediatric Hematology/Oncology, Children's Hospital, Medical Center University of Bonn, Adenauerallee 119, 53113, Bonn, Germany. asimon@ukb.uni-bonn.de
Besuden
Mette
M
Vezmar
Sandra
S
Hasan
Carola
C
Lampe
Dagmar
D
Kreutzberg
Sigrid
S
Glasmacher
Axel
A
Bode
Udo
U
Fleischhack
Gudrun
G
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
D000935:Antifungal Agents; D000970:Antineoplastic Agents; D017964:Itraconazole