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Erschienen in: Medical Oncology 4/2010

01.12.2010 | Original paper

Prophylaxis with itraconazole is more effective than prophylaxis with fluconazole in neutropenic patients with hematological malignancies: a meta-analysis of randomized-controlled trials

verfasst von: Jing Wang, Ping Zhan, Rongfu Zhou, Jingyan Xu, Xiaoyan Shao, Yonggong Yang, Jian Ouyang

Erschienen in: Medical Oncology | Ausgabe 4/2010

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Abstract

Antifungal prophylaxis using fluconazole or itraconazole has been studied for many years but still no consensus has been reached regarding their safety and effectiveness. We performed a systematic meta-analysis to assess the efficacy of fluconazole compared to itraconazole in neutropenic patients with hematological malignancies. We gathered the data for our analysis from MEDLINE, EMBASE, Cochrane-controlled trials register, Cochrane Library, and Science Citation Index (1/1990 to 1/2009) searches. Risk ratio (RR) and 95% confidence intervals (CIs) were calculated using the random effect model. Nine RCTs were identified that were published in full text. Significantly, fewer patients were withdrawn from the studies due to the development of adverse effects with fluconazole prophylaxis when compared with itraconazole (RR 0.45, 95% CI 0.27–0.75, P = 0.002). There were statistically significant differences regarding fungal infections (RR 1.34, 95% CI 1.08–1.67, P = 0.009) and invasive fungal infections (RR 1.33, 95% CI 1.02–1.73, P = 0.03) between the two educations. There were no statistically significant differences regarding overall mortality (RR 0.95, 95% CI 0.77–1.17, P = 0.64), fungal-related mortality (RR 1.28, 95% CI 0.80–2.07, P = 0.31), and proven fungal infections (RR 1.38, 95% CI 0.75–2.53, P = 0.30). The analysis of published evidence reveals that itraconazole administration resulted in significantly fewer episodes of fungal infections and invasive fungal infections compared with fluconazole.
Literatur
1.
Zurück zum Zitat Prentice HG, Kibbler CC, Prentice AG. Towards a targeted, risk-based, antifungal strategy in neutropenic patients. Br J Haematol. 2000;110:273–84.PubMedCrossRef Prentice HG, Kibbler CC, Prentice AG. Towards a targeted, risk-based, antifungal strategy in neutropenic patients. Br J Haematol. 2000;110:273–84.PubMedCrossRef
2.
Zurück zum Zitat Hope WW, Walsh TJ, Denning DW. Laboratory diagnosis of invasive aspergillosis. Lancet Infect Dis. 2005;5(10):609–22.PubMedCrossRef Hope WW, Walsh TJ, Denning DW. Laboratory diagnosis of invasive aspergillosis. Lancet Infect Dis. 2005;5(10):609–22.PubMedCrossRef
3.
Zurück zum Zitat Robenshtok E, Gafter-Gvili A, Goldberg E, et al. Antifungal prophylaxis in cancer patients after chemotherapy or hematopoietic stem-cell transplantation: systematic review and meta-analysis. J Clin Oncol. 2007;25(34):5471–89.PubMedCrossRef Robenshtok E, Gafter-Gvili A, Goldberg E, et al. Antifungal prophylaxis in cancer patients after chemotherapy or hematopoietic stem-cell transplantation: systematic review and meta-analysis. J Clin Oncol. 2007;25(34):5471–89.PubMedCrossRef
4.
Zurück zum Zitat National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in ONCOLOGY™. Prevention and treatment of cancer- related infections. Version 2.2007. Accessed 8 Jan 2007. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in ONCOLOGY™. Prevention and treatment of cancer- related infections. Version 2.2007. Accessed 8 Jan 2007.
5.
Zurück zum Zitat Vardakas KZ, Michalopoulos A, Falagas ME. Fluconazole versus itraconazole for antifungal prophylaxis in neutropenic patients with haematological malignancies: a meta-analysis of randomised-controlled trials. Br J Haematol. 2005;131(1):22–8.PubMedCrossRef Vardakas KZ, Michalopoulos A, Falagas ME. Fluconazole versus itraconazole for antifungal prophylaxis in neutropenic patients with haematological malignancies: a meta-analysis of randomised-controlled trials. Br J Haematol. 2005;131(1):22–8.PubMedCrossRef
6.
Zurück zum Zitat Peter JV, John P, Graham PL, et al. Corticosteroids in the prevention and treatment of acute respiratory distress syndrome (ARDS) in adults: meta-analysis. BMJ. 2008;336:1006–9.PubMedCrossRef Peter JV, John P, Graham PL, et al. Corticosteroids in the prevention and treatment of acute respiratory distress syndrome (ARDS) in adults: meta-analysis. BMJ. 2008;336:1006–9.PubMedCrossRef
7.
Zurück zum Zitat Berlin JA, Laird NM, Sacks HS, et al. A comparison of statistical methods for combining event rates from clinical trials. Stat Med. 1989;8:141–51.PubMedCrossRef Berlin JA, Laird NM, Sacks HS, et al. A comparison of statistical methods for combining event rates from clinical trials. Stat Med. 1989;8:141–51.PubMedCrossRef
8.
Zurück zum Zitat Annaloro C, Oriana A, Tagliaferri E, et al. Efficacy of different prophylactic antifungal regimens in bone marrow transplantation. Haematologica. 1995;80(6):512–7.PubMed Annaloro C, Oriana A, Tagliaferri E, et al. Efficacy of different prophylactic antifungal regimens in bone marrow transplantation. Haematologica. 1995;80(6):512–7.PubMed
9.
Zurück zum Zitat Morgenstern GR, Prentice AG, Prentice HG, et al. A randomized controlled trial of itraconazole versus fluconazole for the prevention of fungal infections in patients with haematological malignancies. UK multicentre antifungal prophylaxis study group. Br J Haematol. 1999;105(4):901–11.PubMedCrossRef Morgenstern GR, Prentice AG, Prentice HG, et al. A randomized controlled trial of itraconazole versus fluconazole for the prevention of fungal infections in patients with haematological malignancies. UK multicentre antifungal prophylaxis study group. Br J Haematol. 1999;105(4):901–11.PubMedCrossRef
10.
Zurück zum Zitat Huijgens PC, Simoons-Smit AM, van Loenen AC, et al. Fluconazole versus itraconazole for the prevention of fungal infections in haemato-oncology. J Clin Pathol. 1999;52(5):376–80.PubMedCrossRef Huijgens PC, Simoons-Smit AM, van Loenen AC, et al. Fluconazole versus itraconazole for the prevention of fungal infections in haemato-oncology. J Clin Pathol. 1999;52(5):376–80.PubMedCrossRef
11.
Zurück zum Zitat Winston DJ, Maziarz RT, Chandrasekar PH, et al. Intravenous and oral itraconazole versus intravenous and oral fluconazole for long-term antifungal prophylaxis in allogeneic hematopoietic stem-cell transplant recipients. A multicenter, randomized trial. Ann Intern Med. 2003;138(9):705–13.PubMed Winston DJ, Maziarz RT, Chandrasekar PH, et al. Intravenous and oral itraconazole versus intravenous and oral fluconazole for long-term antifungal prophylaxis in allogeneic hematopoietic stem-cell transplant recipients. A multicenter, randomized trial. Ann Intern Med. 2003;138(9):705–13.PubMed
12.
Zurück zum Zitat Marr KA, Crippa F, Leisenring W, et al. Itraconazole versus fluconazole for prevention of fungal infections in patients receiving allogeneic stem cell transplants. Blood. 2004;103(4):1527–33.PubMedCrossRef Marr KA, Crippa F, Leisenring W, et al. Itraconazole versus fluconazole for prevention of fungal infections in patients receiving allogeneic stem cell transplants. Blood. 2004;103(4):1527–33.PubMedCrossRef
13.
Zurück zum Zitat Choi SM, Lee DG, Choi JH, et al. Itraconazole oral solution versus fluconazole syrup for prevention of invasive fungal infections in patients receiving hematopoietic stem cell transplantation: prospective, randomized, comparative clinical trial. Infect Chemother. 2005;37(2):71–8. Choi SM, Lee DG, Choi JH, et al. Itraconazole oral solution versus fluconazole syrup for prevention of invasive fungal infections in patients receiving hematopoietic stem cell transplantation: prospective, randomized, comparative clinical trial. Infect Chemother. 2005;37(2):71–8.
14.
Zurück zum Zitat Oren I, Rowe JM, Sprecher H, et al. A prospective randomized trial of itraconazole vs. fluconazole for the prevention of fungal infections in patients with acute leukemia and hematopoietic stem cell transplant recipients. Bone Marrow Transplant. 2006;38(2):127–34.PubMedCrossRef Oren I, Rowe JM, Sprecher H, et al. A prospective randomized trial of itraconazole vs. fluconazole for the prevention of fungal infections in patients with acute leukemia and hematopoietic stem cell transplant recipients. Bone Marrow Transplant. 2006;38(2):127–34.PubMedCrossRef
15.
Zurück zum Zitat Glasmacher A, Cornely O, Ullmann AJ, 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. 2006;57(2):317–25.PubMedCrossRef Glasmacher A, Cornely O, Ullmann AJ, 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. 2006;57(2):317–25.PubMedCrossRef
16.
Zurück zum Zitat Ito Y, Ohyashiki K, Yoshida I, et al. The prophylactic effect of itraconazole capsules and fluconazole capsules for systemic fungal infections in patients with acute myeloid leukemia and myelodysplastic syndromes: a Japanese multicenter randomized, controlled study. Int J Hematol. 2007;85(2):121–7.PubMedCrossRef Ito Y, Ohyashiki K, Yoshida I, et al. The prophylactic effect of itraconazole capsules and fluconazole capsules for systemic fungal infections in patients with acute myeloid leukemia and myelodysplastic syndromes: a Japanese multicenter randomized, controlled study. Int J Hematol. 2007;85(2):121–7.PubMedCrossRef
17.
Zurück zum Zitat Prentice AG, Glasmacher A, Djulbegovic B. In meta-analysis itraconazole is superior to fluconazole for prophylaxis of systemic fungal infection in the treatment of haematological malignancy. Br J Haematol. 2006;132(5):656–8.PubMedCrossRef Prentice AG, Glasmacher A, Djulbegovic B. In meta-analysis itraconazole is superior to fluconazole for prophylaxis of systemic fungal infection in the treatment of haematological malignancy. Br J Haematol. 2006;132(5):656–8.PubMedCrossRef
18.
Zurück zum Zitat Cornely OA, Böhme A, Buchheidt D, 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. 2009;94(1):113–22.PubMedCrossRef Cornely OA, Böhme A, Buchheidt D, 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. 2009;94(1):113–22.PubMedCrossRef
19.
Zurück zum Zitat Glasmacher A, Prentice A, Gorschlüter M, et al. Itraconazole prevents invasive fungal infections in neutropenic patients treated for haematological malignancies: Evidence from a meta-analysis of 3, 597 patients. J Clin Oncol. 2003;21(24):4615–26.PubMedCrossRef Glasmacher A, Prentice A, Gorschlüter M, et al. Itraconazole prevents invasive fungal infections in neutropenic patients treated for haematological malignancies: Evidence from a meta-analysis of 3, 597 patients. J Clin Oncol. 2003;21(24):4615–26.PubMedCrossRef
20.
Zurück zum Zitat Bow EJ, Laverdière M, Lussier N, et al. Antifungal prophylaxis for severely neutropenic chemotherapy recipients: a meta analysis of randomized-controlled clinical trials. Cancer. 2002;94(12):3230–46.PubMedCrossRef Bow EJ, Laverdière M, Lussier N, et al. Antifungal prophylaxis for severely neutropenic chemotherapy recipients: a meta analysis of randomized-controlled clinical trials. Cancer. 2002;94(12):3230–46.PubMedCrossRef
21.
Zurück zum Zitat Tamura K, Drew R. Antifungal prophylaxis in adult hematopoietic stem cell transplant recipients. Drugs Today (Barc). 2008;44(7):515–30.CrossRef Tamura K, Drew R. Antifungal prophylaxis in adult hematopoietic stem cell transplant recipients. Drugs Today (Barc). 2008;44(7):515–30.CrossRef
22.
Zurück zum Zitat Maertens J. Evaluating prophylaxis of invasive fungal infections in patients with haematologic malignancies. Eur J Haematol. 2007;78(4):275–82.PubMedCrossRef Maertens J. Evaluating prophylaxis of invasive fungal infections in patients with haematologic malignancies. Eur J Haematol. 2007;78(4):275–82.PubMedCrossRef
Metadaten
Titel
Prophylaxis with itraconazole is more effective than prophylaxis with fluconazole in neutropenic patients with hematological malignancies: a meta-analysis of randomized-controlled trials
verfasst von
Jing Wang
Ping Zhan
Rongfu Zhou
Jingyan Xu
Xiaoyan Shao
Yonggong Yang
Jian Ouyang
Publikationsdatum
01.12.2010
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 4/2010
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-009-9339-0

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