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Efficacy of caspofungin as salvage therapy for invasive aspergillosis compared to standard therapy in a historical cohort

  • J. W. HiemenzEmail author
  • I. I. Raad
  • J. A. Maertens
  • R. Y. Hachem
  • A. J. Saah
  • C. A. Sable
  • J. A. Chodakewitz
  • M. E. Severino
  • P. Saddier
  • R. S. Berman
  • D. M. Ryan
  • M. J. DiNubile
  • T. F. Patterson
  • D. W. Denning
  • T. J. Walsh
Article

Abstract

In a non-comparative study, caspofungin was effective salvage therapy for approximately half of the patients refractory to or intolerant of standard antifungal agents for invasive aspergillosis. To establish a frame of reference for these results, we compared the response to caspofungin with responses to other antifungal agents in a historical cohort of similar patients. The efficacy could be evaluated in 83 patients who received caspofungin 50 mg daily after a 70-mg loading dose. The historical control group, identified through a retrospective review of medical records, included 214 evaluable patients possibly refractory to or intolerant of ≥1 week of standard antifungal therapy. All patients had documented invasive aspergillosis. Favorable response was defined as a complete or partial response to therapy. Underlying diseases, baseline neutropenia, corticosteroid use, and sites of infection were similar in both studies. Most patients had received amphotericin B formulations and/or itraconazole, and were refractory to standard therapy. Favorable response rates were 45% with caspofungin and 16% with standard therapy. The unadjusted odds ratio for a favorable response (caspofungin/standard therapy) was 4.1 (95% confidence interval: 2.2, 7.5). After adjusting for potential imbalances in the frequency of disseminated infection, neutropenia, steroid use, and bone marrow transplantation between groups, the odds ratio remained at 4.1 (2.1, 7.9). Although only tentative conclusions about relative efficacy can be drawn from retrospective comparisons, caspofungin appeared to be at least as efficacious as an amphotericin B formulation and/or itraconazole for the treatment of invasive aspergillosis in patients refractory to or intolerant of their initial antifungal therapy.

Keywords

Itraconazole Voriconazole Antifungal Therapy Invasive Aspergillosis Caspofungin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The authors thank Prof. Dr. Marc Boogaerts for his many contributions to these studies, Dr. Nicholas Kartsonis and Arlene Taylor for their careful review of our report, and Joann DiLullo and Karyn Davis for their expert assistance in the preparation of this manuscript.

Disclosures

Merck & Co., Inc., which markets caspofungin under the brand name Cancidas, sponsored and funded this study. Current and former employees of the sponsor (indicated on the title page) may own stock or stock options in the company. All non-Merck authors have served as investigators on Merck studies. The sponsor formally reviewed a penultimate draft. All co-authors approved an essentially final version of the manuscript.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • J. W. Hiemenz
    • 1
    Email author
  • I. I. Raad
    • 2
  • J. A. Maertens
    • 3
  • R. Y. Hachem
    • 2
  • A. J. Saah
    • 4
  • C. A. Sable
    • 4
  • J. A. Chodakewitz
    • 4
  • M. E. Severino
    • 4
  • P. Saddier
    • 4
  • R. S. Berman
    • 4
  • D. M. Ryan
    • 4
  • M. J. DiNubile
    • 4
  • T. F. Patterson
    • 5
  • D. W. Denning
    • 6
  • T. J. Walsh
    • 7
  1. 1.Division of Hematology/OncologyUniversity of Florida College of MedicineGainesvilleUSA
  2. 2.M.D. Anderson Cancer CenterHoustonUSA
  3. 3.UZ GasthuisbergLeuvenBelgium
  4. 4.Merck Research LaboratoriesWest PointUSA
  5. 5.The University of Texas Health Science Center and South Texas Veterans Health Care SystemSan AntonioUSA
  6. 6.The University of Manchester, Manchester Academic Health Science CentreManchesterUK
  7. 7.National Cancer InstituteBethesdaUSA

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