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Blood, 15 February 2004, Vol. 103, No. 4, pp. 1527-1533.
Prepublished online as a Blood First Edition Paper on October 2, 2003; DOI 10.1182/blood-2003-08-2644.
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TRANSPLANTATION
Itraconazole versus fluconazole for prevention of fungal infections in patients receiving allogeneic stem cell transplants
Kieren A. Marr,
Fulvio Crippa,
Wendy Leisenring,
Maggie Hoyle,
Michael Boeckh,
S. Arunmozhi Balajee,
W. Garrett Nichols,
Benjamin Musher, and
Lawrence Corey
From the Program of Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, WA; the Program of Clinical Statistics, Fred Hutchinson Cancer Research Center, Seattle, WA; the Department of Medicine, University of Washington, Seattle; and the Department of Laboratory Medicine, University of Washington, Seattle.
Prophylactic fluconazole prevents candidiasis; however, this drug has no activity against molds. We performed a randomized trial to determine whether prophylactic itraconazole prevents invasive mold infections (IMIs). A total of 304 patients receiving allogeneic stem cell transplants (SCT) were randomized to receive fluconazole (400 mg/d) or itraconazole (oral solution 2.5 mg/kg 3 times daily, or intravenous 200 mg daily) for 180 days after SC transplantation, or until 4 weeks after discontinuation of graft-versus-host disease (GVHD) therapy. Proven or probable invasive fungal infections (IFI) were evaluated by intent-to-treat and "on-treatment" analyses. More patients in the itraconazole arm developed hepatotoxicities, and more patients were discontinued from itraconazole because of toxicities or gastrointestinal (GI) intolerance (36% versus 16%, P < .001). Intent-to-treat analysis demonstrated no difference in the incidence of IFI during the intended study period (fluconazole 16% versus itraconazole 13%, P = .46); however, fewer patients in the itraconazole arm developed IFI on treatment (fluconazole 15% versus itraconazole 7%, P = .03). Itraconazole provided better protection against IMI (fluconazole 12% versus itraconazole 5%, P = .03), but similar protection against candidiasis (3% versus 2%, P = .69). There was no difference in overall or fungal-free survival. Itraconazole appears to prevent IMI in the subset of patients who tolerate the drug; however, toxicities and poor tolerability limit its success as prophylactic therapy.
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