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Letters to the Editor

Caspofungin Versus Liposomal Amphotericin B

Are They Really Comparable?

Walsh, Thomas J. MD; 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; Ann Wise, Beth 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

Author Information
The Pediatric Infectious Disease Journal: October 2010 - Volume 29 - Issue 10 - p 986-987
doi: 10.1097/INF.0b013e3181f2d88c
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Reply:

Invasive fungal infections are important causes of morbidity and mortality in immunocompromised pediatric patents.1,2 This randomized clinical trial of empiric antifungal therapy in persistently febrile neutropenic children and adolescents is a critically important study, as it is one of the few prospective randomized controlled trials of antifungal therapy in the pediatric population.3 There are formidable challenges in conducting such studies.

We were indeed very careful in the manuscript not to establish firm conclusions, and we clearly acknowledged the study's limitations. We state that the principal objective of this study was to estimate indices of safety, tolerability, and efficacy of caspofungin and l-AmB. We also noted that because the sample size was not intended to test specific hypotheses, the analyses displayed present point estimates and confidence intervals rather than P-values. We concluded that caspofungin and l-AmB were comparable in tolerability, safety, and efficacy as empiric antifungal therapy. Rather than using statistically based terms, such as “noninferior” or “equivalent,” we were careful to use the term “comparable” which signifies “similar.”

Consistent with this conclusion, is the observation that the safety, tolerability, and efficacy data for caspofungin and liposomal amphotericin B in pediatric patients, albeit limited, are similar to those found in the substantially larger study of empiric antifungal therapy in persistently febrile neutropenic adults.4 We also were meticulous in designing the pediatric study with dosages of caspofungin and liposomal amphotericin B that provided comparable plasma exposure to those used in adults.5 Moreover, the findings from the study of caspofungin's efficacy in pediatric patients with documented fungal infections, predominantly candidemia, provided important complementary data for caspofungin as empiric therapy.6 The results of the pediatric study, as well the comparable pharmacokinetic plasma exposure, coupled with the data from the similarly designed but larger studies in adult patients warrant the conservative conclusion that caspofungin and l-AmB were comparable in tolerability, safety, and efficacy as empiric antifungal therapy in pediatric patients.

Thomas J. Walsh, MD

Immunocompromised Host Section

Pediatric Oncology Branch

National Cancer Institute

Bethesda, MD

Transplantation-Oncology Infectious Diseases Program

Weill Cornell Medical College of Cornell University

New York, NY

Johan A. Maertens, MD

Acute Leukemia and Stem Cell Transplantation Unit

Department of Hematology

University Hospitals Leuven, Campus

Gasthuisberg Leuven, Belgium

Luis Madero, MD

Pediatric Hematology—Oncology

Hospital Universitario Niño Jesus

Madrid, Spain

Anne F. Reilly, MD

Division of Oncology

Children's Hospital of Philadelphia

Thomas Lehrnbecher, MD

Pediatric Hematology and Oncology

Frankfurt University

Frankfurt, Germany

Andreas H. Groll, MD

Infectious Disease Research Program

Department of Pediatric Hematology/Oncology

University Children's Hospital of Münster

Münster, Germany

Hasan S. Jafri, MD

Division of Pediatric Infectious Diseases

Department of Pediatrics

University of Texas Southwestern Medical Center

Dallas, TX

Clinical Development, MedImmune

Gaithersburg, MD

Michael Green, MD

Division of Infectious Diseases

Departments of Pediatrics, Surgery & Clinical, and Translational Science

Children's Hospital of Pittsburgh

Pittsburgh, PA

Joseph J. Nania, MD

Division of Pediatric Infectious Diseases

Department of Pediatrics

Vanderbilt University

Nashville, TN

Michael R. Bourque, MS

Beth Ann Wise, MSEd

Kim M. Strohmaier, BS

Arlene F. Taylor, MS

Nicholas A. Kartsonis, MD

Joseph W. Chow, MD

Merck Research Laboratories North Wales, PA

Carola A. S. Arndt, MD

Mayo Clinic

Rochester, MN

Ben E. dePauw, MD

Blood Transfusion and Transplant Immunology

Radboud University

Nijmegen Medical Centre

Nijmegen, Netherlands

REFERENCES

1. Maertens JA, Madero L, Reilly AF, et al. A randomized, double blind, multicenter study of caspofungin versus liposomal amphotericin B for empiric antifungal therapy in pediatric patients with persistent fever and neutropenia. Pediatr Infect Dis J. 2010;29:415–420.
2. Dornbusch HJ, Manzoni P, Roilides E, et al. Invasive fungal infections in children. Pediatr Infect Dis J. 2009;28:734–737.
3. Steinbach WJ, Walsh TJ. Mycoses in pediatric patients. Infect Dis Clin North Am. 2006;20:663–678.
4. Walsh TJ, Teppler H, Donowitz GR, et al. Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med. 2004;351:1391–1402.
5. Walsh TJ, Adamson PC, Seibel NL, et al. Pharmacokinetics, safety, and tolerability of caspofungin in children and adolescents. Antimicrob Agents Chemother. 2005;49:4536–4545.
6. Zaoutis TE, Jafri HS, Huang LM, et al. A prospective, multicenter study of caspofungin for the treatment of documented Candida or Aspergillus infections in pediatric patients. Pediatrics. 2009;123:877–884.
© 2010 Lippincott Williams & Wilkins, Inc.