1887

Abstract

In a clinical non-trial setting, the efficacy and safety of caspofungin was compared with liposomal amphotericin B for the management of febrile neutropenia or invasive fungal infections in 73 episodes in patients with haematological malignancy. There were fewer episodes of drug toxicity with caspofungin than liposomal amphotericin B (58.3 vs 83.7 %, =0.02). The favourable response rate for episodes of febrile neutropenia treated with caspofungin or liposomal amphotericin B was similar at 37.5 and 53.8 %, respectively, but more breakthrough fungal infections occurred with caspofungin than with liposomal amphotericin B (33.3 vs 0 %, <0.05) in these patients who did not receive antifungal prophylaxis. None of four episodes of candidaemia or hepatosplenic candidiasis responded to caspofungin compared with three of four episodes treated with liposomal amphotericin B. Mortality was significantly higher with caspofungin treatment compared with liposomal amphotericin B (6/24 vs 2/49, =0.01), mainly due to an excess of fungal infections (=0.04). Caspofungin treatment was a significant independent predictor of mortality [odds ratio=7.6 (95 % confidence interval 1.2–45.5)] when sepsis severity, prolonged neutropenia and length of antifungal therapy were considered in a multiple logistic regression model. In clinical practice, there is a suggestion that caspofungin may not be as effective as liposomal amphotericin B in preventing breakthrough invasive fungal infections in febrile neutropenia or in preventing fungus-related deaths. Because of the potential biases in this observational study, these preliminary findings should be interpreted with caution and clarified with a larger cohort of patients.

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2006-10-01
2019-10-18
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References

  1. Ascioglu, S., Rex, J. H., de Pauw, B. & 17 other authors ( 2002; ). Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis 34, 7–14.[CrossRef]
    [Google Scholar]
  2. Bowman, J. C., Hicks, P. S., Kurtz, M. B., Rosen, H., Schmatz, D. M., Liberator, P. A. & Douglas, C. M. ( 2002; ). The antifungal echinocandin caspofungin acetate kills growing cells of Aspergillus fumigatus in vitro. Antimicrob Agents Chemother 46, 3001–3012.[CrossRef]
    [Google Scholar]
  3. Caillot, D., Casanovas, O., Berbard, A. & 10 other authors ( 1997; ). Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery. J Clin Oncol 15, 139–147.
    [Google Scholar]
  4. Caillot, D., Couaillier, J.-F., Bernard, A. & 8 other authors ( 2001; ). Increasing volume and changing characteristics of invasive pulmonary aspergillosis on sequential thoracic computed tomography scans in patients with neutropenia. J Clin Oncol 19, 253–259.
    [Google Scholar]
  5. Candoni, A., Mestroni, R., Damiani, D., Tiribelli, M., Michelutti, A., Silvestri, F., Castelli, M., Viale, P. & Fanin, R. ( 2005; ). Caspofungin as first line therapy of pulmonary invasive fungal infections in 32 immunocompromised patients with hematologic malignancies. Eur J Haematol 75, 227–233.[CrossRef]
    [Google Scholar]
  6. Coiffier, B., Lepage, E., Brière, J. & 10 other authors ( 2002; ). CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 346, 235–242.[CrossRef]
    [Google Scholar]
  7. Denning, D. ( 2003; ). Echinocandin antifungal drugs. Lancet 362, 1142–1151.[CrossRef]
    [Google Scholar]
  8. Ellis, M., Hedstrom, U., Jumaa, P. & Bener, A. ( 2003; ). Epidemiology, presentation, management and outcome of candidemia in a tertiary care teaching hospital in the United Arab Emirates, 1995–2001. Med Mycol 41, 521–528.[CrossRef]
    [Google Scholar]
  9. EORTC, International Antimicrobial Therapy Cooperative Group ( 1989; ). Empirical antifungal therapy in febrile granulocytopenic patients. Am J Med 86, 668–672.[CrossRef]
    [Google Scholar]
  10. Farag, S. S., Ruppert, A. S., Mrózek, K. & 15 other authors ( 2005; ). Outcome of induction and postremission therapy in younger adults with acute myeloid leukemia with normal karyotype: a cancer and leukemia group B study. J Clin Oncol 23, 482–493.
    [Google Scholar]
  11. Hughes, W. T., Armstrong, D., Bodey, G. P. & 8 other authors ( 2002; ). 2002 Guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 34, 730–751.[CrossRef]
    [Google Scholar]
  12. Kami, M., Kishi, Y., Hamaki, T. & 11 other authors ( 2002; ). The value of the chest computed tomography halo sign in the diagnosis of invasive pulmonary aspergillosis. An autopsy-based retrospective study of 48 patients. Mycoses 45, 287–294.[CrossRef]
    [Google Scholar]
  13. Karthaus, M. & Cornely, O. ( 2005; ). Recent developments in the management of invasive fungal infections in patients with hematological malignancies. Ann Hematol 84, 207–216.[CrossRef]
    [Google Scholar]
  14. Kontoyiannis, D. P. & Lewis, R. E. ( 2004; ). Toward more effective antifungal therapy: the prospects of combination therapy. Br J Haematol 126, 165–175.[CrossRef]
    [Google Scholar]
  15. Lin, S.-J., Schranz, J. & Teutsch, S. ( 2001; ). Aspergillosis case-fatality rate: systematic review of the literature. Clin Inf Dis 32, 358–366.[CrossRef]
    [Google Scholar]
  16. Maertens, J., Raad, I., Petrikkos, G. & 10 other authors ( 2004; ). Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy. Clin Inf Dis 39, 1563–1571.[CrossRef]
    [Google Scholar]
  17. Medical Research Council Working Party on Leukemia in Adults ( 2006; ). Medical Research Council Acute Lymphoblastic Leukemia Trial XII (ULALL XII), Version 4.1, February 2006. Joint Trial with Eastern Cooperative Oncology Group (ECOG) – E2993. Protocol for Adults with ALL. Modified for Intrathecal Therapy and Philadelphia Positive ALL, July 2002. Revised May 2005, February 2006. Available at http://www.ctsu.ox.ac.uk/projects/ukallxii/
  18. Mora-Duarte, J., Betts, R., Rotstein, C. & 7 other authors ( 2002; ). Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med 347, 2020–2029.[CrossRef]
    [Google Scholar]
  19. Mukherjee, P. K., Sheehan, D. J., Hitchcock, C. A. & Ghannoum, M. A. ( 2005; ). Combination treatment of invasive fungal infections. Clin Microbiol Rev 18, 163–194.[CrossRef]
    [Google Scholar]
  20. Ostrosky-Zeichner, L., Marr, K., Rex, J. & Cohen, S. ( 2003; ). Amphotericin B: time for a new “gold standard”. Clin Inf Dis 37, 415–425.[CrossRef]
    [Google Scholar]
  21. Pappas, P. G., Rex, J. H., Sobel, J. D., Filler, S. G., Dismukes, W. E., Walsh, T. J. & Edwards, J. E. ( 2004; ). Guidelines for treatment of candidiasis. Clin Inf Dis 38, 161–189.[CrossRef]
    [Google Scholar]
  22. Walsh, T. J., Teppler, H., Donowitz, G. R. & 8 other authors ( 2004; ). Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med 351, 1391–1402.[CrossRef]
    [Google Scholar]
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