Journal of Clinical Oncology, Vol 21, Issue 24
(December), 2003: 4615-4626
© 2003 American Society for Clinical Oncology
Itraconazole Prevents Invasive Fungal Infections in Neutropenic Patients Treated for Hematologic Malignancies: Evidence From a Meta-Analysis of 3,597 Patients
Axel Glasmacher,
Archibald Prentice,
Marcus Gorschlüter,
Steffen Engelhart,
Corinna Hahn,
Benjamin Djulbegovic,
Ingo G.H. Schmidt-Wolf
From the Department of Internal Medicine I and Institute for Hygiene and Public Health, University of Bonn, Bonn, Germany; DCL Haematology, Derriford Hospital, Plymouth, United Kingdom; and the Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center & Research Institute, University of South Florida, Tampa, FL.
Address reprint requests to Axel Glasmacher, MD, PhD, Department of Internal Medicine I, University of Bonn, 53105 Bonn, Germany; e-mail: glasmacher{at}uni-bonn.de
Purpose: Efficacy of antifungal prophylaxis has not yet been convincingly proven in numerous trials of various antifungals. New evidence and the anti-Aspergillus efficacy of itraconazole prompted a new look at the data for the prevention of invasive fungal infections.
Patients and Methods: Randomized, controlled studies with itraconazole for antifungal prophylaxis in neutropenic patients with hematologic malignancies were identified from electronic databases and hand searching.
Results: Thirteen randomized trials included 3,597 patients who were assessable for invasive fungal infections. Itraconazole reduced the incidence of invasive fungal infection (mean relative risk reduction, 40% ± 13%; P = .002), the incidence of invasive yeast infections (mean, 53% ± 19%; P = .004) and the mortality from invasive fungal infections (mean, 35% ± 17%; P = .04) significantly. The incidence of invasive Aspergillus infections was only reduced in trials using the itraconazole cyclodextrine solution (mean, 48% ± 21%; P = .02) and not itraconazole capsules (mean, 75% ± 73% increase; P = .3). The overall mortality was not changed. Adverse effects were rare, hypokalemia was noted in three studies, and a higher rate of drug discontinuation was found in trials that compared itraconazole cyclodextrine solution to a control without cyclodextrine. The effect of prophylaxis was clearly associated with a higher bioavailable dose of itraconazole.
Conclusion: Antifungal prophylaxis with itraconazole effectively prevents proven invasive fungal infections and—shown for the first time for antifungal prophylaxis—reduces mortality from these infections and the rate of invasive Aspergillus infections in neutropenic patients with hematologic malignancies. Adequate doses of the oral cyclodextrine solution (at least 400 mg/d) or IV formulations (200 mg/d) of itraconazole are necessary for these effects.
Supported in part by Ortho-Biotech Ltd. (division of Janssen-Cilag, Neuss, Germany) and by Leukaemie-Initiative Bonn.
Presented in part at the Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, December 16–19, 2001; the American Society of Hematology meeting, Philadelphia, PA, December 6–10, 2002; and the 29th Annual Meeting of the European Group for Blood and Marrow Transplantation, July 20–23, 2003.
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Facebook  Reddit  Technorati  Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Michallet and J. I. Ito
Approaches to the Management of Invasive Fungal Infections in Hematologic Malignancy and Hematopoietic Cell Transplantation
J. Clin. Oncol.,
July 10, 2009;
27(20):
3398 - 3409.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Maschmeyer
Prevention of mould infections
J. Antimicrob. Chemother.,
May 1, 2009;
63(suppl_1):
i27 - i30.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. A. Cornely, A. Bohme, D. Buchheidt, H. Einsele, W. J. Heinz, M. Karthaus, S. W. Krause, W. Kruger, G. Maschmeyer, O. Penack, et al.
Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology
Haematologica,
January 1, 2009;
94(1):
113 - 122.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. G. Masterton, A. Galloway, G. French, M. Street, J. Armstrong, E. Brown, J. Cleverley, P. Dilworth, C. Fry, A. D. Gascoigne, et al.
Guidelines for the management of hospital-acquired pneumonia in the UK: Report of the Working Party on Hospital-Acquired Pneumonia of the British Society for Antimicrobial Chemotherapy
J. Antimicrob. Chemother.,
July 1, 2008;
62(1):
5 - 34.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Dungarwalla, S. O. Evans, U. Riley, D. Catovsky, C. E. Dearden, and E. Matutes
High dose methylprednisolone and rituximab is an effective therapy in advanced refractory chronic lymphocytic leukemia resistant to fludarabine therapy
Haematologica,
March 1, 2008;
93(3):
475 - 476.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Robenshtok, A. Gafter-Gvili, E. Goldberg, M. Weinberger, M. Yeshurun, L. Leibovici, and M. Paul
Antifungal Prophylaxis in Cancer Patients After Chemotherapy or Hematopoietic Stem-Cell Transplantation: Systematic Review and Meta-Analysis
J. Clin. Oncol.,
December 1, 2007;
25(34):
5471 - 5489.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. A. Cornely, J. Maertens, D. J. Winston, J. Perfect, A. J. Ullmann, T. J. Walsh, D. Helfgott, J. Holowiecki, D. Stockelberg, Y.-T. Goh, et al.
Posaconazole vs. Fluconazole or Itraconazole Prophylaxis in Patients with Neutropenia
N. Engl. J. Med.,
January 25, 2007;
356(4):
348 - 359.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. E. De Pauw and J. P. Donnelly
Prophylaxis and Aspergillosis -- Has the Principle Been Proven?
N. Engl. J. Med.,
January 25, 2007;
356(4):
409 - 411.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. W. Mouton, A. van Peer, K. de Beule, A. Van Vliet, J. P. Donnelly, and P. A. Soons
Pharmacokinetics of Itraconazole and Hydroxyitraconazole in Healthy Subjects after Single and Multiple Doses of a Novel Formulation
Antimicrob. Agents Chemother.,
December 1, 2006;
50(12):
4096 - 4102.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Glasmacher, O. Cornely, A. J. Ullmann, U. Wedding, H. Bodenstein, H. Wandt, C. Boewer, R. Pasold, H.-H. Wolf, M. Hanel, et al.
An open-label randomized trial comparing itraconazole oral solution with fluconazole oral solution for primary prophylaxis of fungal infections in patients with haematological malignancy and profound neutropenia
J. Antimicrob. Chemother.,
February 1, 2006;
57(2):
317 - 325.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. N. Mattiuzzi, G. Alvarado, F. J. Giles, L. Ostrosky-Zeichner, J. Cortes, S. O'Brien, S. Verstovsek, S. Faderl, X. Zhou, I. I. Raad, et al.
Open-Label, Randomized Comparison of Itraconazole versus Caspofungin for Prophylaxis in Patients with Hematologic Malignancies
Antimicrob. Agents Chemother.,
January 1, 2006;
50(1):
143 - 147.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Glasmacher and A. Prentice
The role of meta-analysis in the evaluation of antifungal prophylaxis: authors' response
J. Antimicrob. Chemother.,
January 1, 2006;
57(1):
152 - 154.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. J. Bow
Of Yeasts and Hyphae: A Hematologist's Approach to Antifungal Therapy
Hematology,
January 1, 2006;
2006(1):
361 - 367.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Glasmacher, A. Prentice, M. Gorschluter, S. Engelhart, C. Hahn, B. Djulbegovic, and I. G.H. Schmidt-Wolf
In Reply:
J. Clin. Oncol.,
December 20, 2005;
23(36):
9429 - 9432.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. C. Gotzsche and H. K. Johansen
Misleading Statements in Industry-Sponsored Meta-Analysis of Itraconazole
J. Clin. Oncol.,
December 20, 2005;
23(36):
9428 - 9429.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Glasmacher, C. Hahn, M. von Lilienfeld-Toal, K. Orlopp, I. Schmidt-Wolf, and A. Prentice
Itraconazole for Antifungal Prophylaxis in Neutropenic Patients: An Update of a Meta-Analysis with Now 3846 Patients.
Blood (ASH Annual Meeting Abstracts),
November 16, 2005;
106(11):
3224 - 3224.
[Abstract]
|
|
|
|
|
|
|
W. H. Kruger, J. Bohlius, O. A. Cornely, H. Einsele, H. Hebart, G. Massenkeil, S. Schuttrumpf, G. Silling, A. J. Ullmann, D. T. Waldschmidt, et al.
Antimicrobial prophylaxis in allogeneic bone marrow transplantation. Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Haematology and Oncology
Ann. Onc.,
August 1, 2005;
16(8):
1381 - 1390.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Winston, C. Emmanouilides, K. Bartoni, G. J. Schiller, R. Paquette, M. C. Territo, K. A. Marr, and M. Boeckh
Elimination of Aspergillus infection in allogeneic stem cell transplant recipients with long-term itraconazole prophylaxis: prevention is better than treatment
Blood,
September 1, 2004;
104(5):
1581 - 1582.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. R. Wingard, W. G. Nichols, and G. B. McDonald
Supportive Care
Hematology,
January 1, 2004;
2004(1):
372 - 389.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
