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A Randomized, Double-Blind, Multicenter Study of Caspofungin Versus Liposomal Amphotericin B for Empiric Antifungal Therapy in Pediatric Patients With Persistent Fever and Neutropenia

Maertens, Johan A. MD*; Madero, Luis MD; Reilly, Anne F. MD; Lehrnbecher, Thomas MD§; Groll, Andreas H. MD; Jafri, Hasan S. MD; Green, Michael MD**; Nania, Joseph J. MD††; Bourque, Michael R. MS‡‡; Wise, Beth Ann MSEd‡‡; Strohmaier, Kim M. BS§§; Taylor, Arlene F. MS¶¶; Kartsonis, Nicholas A. MD‡‡; Chow, Joseph W. MD‡‡; Arndt, Carola A. S. MD∥∥; dePauw, Ben E. MD***; Walsh, Thomas J. MD†††for the Caspofungin Pediatric Study Group

The Pediatric Infectious Disease Journal: May 2010 - Volume 29 - Issue 5 - p 415-420
doi: 10.1097/INF.0b013e3181da2171
Original Studies

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/m2 loading dose on day 1, then 50 mg/m2 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.


From the *Acute Leukemia and Stem Cell Transplantation Unit, Department of Hematology, University Hospitals Leuven, Campus Gasthuisberg, Leuven, Belgium; †Pediatrics Hematology-Oncology, Hospital Universitario Niño Jesus, Madrid, Spain; ‡Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA; §Pediatric Hematology and Oncology, University of Frankfurt, Frankfurt, Germany; ¶Infectious Disease Research Program, Department of Pediatric Hematology/Oncology, University Children's Hospital of Münster, Münster, Germany; ∥Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX; **Division of Infectious Diseases, Departments of Pediatrics, Surgery & Clinical and Translational Science, Children's Hospital of Pittsburgh, Pittsburgh, PA; ††Vanderbilt University, Nashville, TN; ‡‡Clinical Research–Infectious Diseases, Merck Research Laboratories, North Wales, PA; §§Medical Communications, Merck Research Laboratories, North Wales, PA; ¶¶Biostatistics & Research Decision Sciences, Merck Research Laboratories, North Wales, PA; ∥∥Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN; ***Blood Transfusion and Transplant Immunology, Radboud University, Nijmegen Medical Centre, Nijmegen, Netherlands; †††Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD.

Accepted for publication December 9, 2009.

Hasan S. Jafri is currently at Infectious Disease, Clinical Research and Development, MedImmune, Gaithersburg, MD.

Address for correspondence: Dr Thomas J. Walsh, MD, Pediatric Oncology Branch, National Cancer Institute, CRC 1-5750, 10 Center Drive, Bethesda, MD 20892. E-mail:

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© 2010 Lippincott Williams & Wilkins, Inc.