title: A randomized, double-blind, multicenter study of caspofungin versus liposomal amphotericin B for empiric antifungal therapy in pediatric patients with persistent fever and neutropenia.
abstract: BACKGROUND
  Persistently febrile neutropenic children at risk for invasive fungal infections receive empiric antifungal therapy as a standard of care. However, little is known about the role of echinocandins and liposomal amphotericin B (L-AmB) for empiric antifungal therapy in pediatric patients.
  
  
  METHODS
  Patients between the ages of 2 to 17 years with persistent fever and neutropenia were randomly assigned to receive caspofungin (70 mg/m loading dose on day 1, then 50 mg/m daily [maximum 70 mg/d]) or L-AmB (3 mg/kg daily) in a 2:1 ratio. Evaluation of safety was the primary objective of the study. Efficacy was also evaluated, with a successful outcome defined as fulfilling all components of a prespecified 5-part composite endpoint. Suspected invasive fungal infections were evaluated by an independent, treatment-blinded adjudication committee.
  
  
  RESULTS
  Eighty-two patients received study therapy (caspofungin 56, L-AmB 26), and 81 were evaluated for efficacy (caspofungin 56; L-AmB 25). Outcomes for safety and efficacy endpoints were similar for both study arms. Adverse drug-related event rates [95% confidence interval] were similar between the caspofungin and L-AmB groups (clinical 48.2% [34.7-62.0] versus 46.2% [26.6-66.6]; laboratory 10.7% [4.0-21.9] versus 19.2% [6.6-39.4]). Serious drug-related adverse events occurred in 1 (1.8%) of caspofungin-treated patients and 3 (11.5%) of L-AmB-treated patients. Overall success rates [95% CI] were 46.4% [33.4-59.5] for caspofungin and 32.0% [13.7-50.3] for L-AmB.
  
  
  CONCLUSIONS
  Caspofungin and L-AmB were comparable in tolerability, safety, and efficacy as empiric antifungal therapy for persistently febrile neutropenic pediatric patients.
authors.affiliation: Acute Leukemia and Stem Cell Transplantation Unit, Department of Hematology, University Hospitals Leuven, Campus Gasthuisberg, Leuven, Belgium.
authors.forename: Johan A
authors.initials: JA
authors.lastname: Maertens
authors.forename: Luis
authors.initials: L
authors.lastname: Madero
authors.forename: Anne F
authors.initials: AF
authors.lastname: Reilly
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehrnbecher
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Groll
authors.forename: Hasan S
authors.initials: HS
authors.lastname: Jafri
authors.forename: Michael
authors.initials: M
authors.lastname: Green
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Nania
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bourque
authors.forename: Beth Ann
authors.initials: BA
authors.lastname: Wise
authors.forename: Kim M
authors.initials: KM
authors.lastname: Strohmaier
authors.forename: Arlene F
authors.initials: AF
authors.lastname: Taylor
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Kartsonis
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Chow
authors.forename: Carola A S
authors.initials: CA
authors.lastname: Arndt
authors.forename: Ben E
authors.initials: BE
authors.lastname: DePauw
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Walsh
mesh_terms: D000293:Adolescent; D000666:Amphotericin B / Q000008:administration & dosage* / Q000009:adverse effects; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000077336:Caspofungin; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D054714:Echinocandins / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005335:Fever of Unknown Origin / Q000188:drug therapy*; D006801:Humans; D055666:Lipopeptides; D008297:Male; D009503:Neutropenia / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; C068538:liposomal amphotericin B; D000666:Amphotericin B; D000077336:Caspofungin