title: Itraconazole versus fluconazole for prevention of fungal infections in patients receiving allogeneic stem cell transplants.
abstract: 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.
authors.affiliation: Program of Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. kmarr@fhcrc.org
authors.forename: Kieren A
authors.initials: KA
authors.lastname: Marr
authors.forename: Fulvio
authors.initials: F
authors.lastname: Crippa
authors.forename: Wendy
authors.initials: W
authors.lastname: Leisenring
authors.forename: Maggie
authors.initials: M
authors.lastname: Hoyle
authors.forename: Michael
authors.initials: M
authors.lastname: Boeckh
authors.forename: S Arunmozhi
authors.initials: SA
authors.lastname: Balajee
authors.forename: W Garrett
authors.initials: WG
authors.lastname: Nichols
authors.forename: Benjamin
authors.initials: B
authors.lastname: Musher
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001228:Aspergillosis / Q000401:mortality / Q000517:prevention & control*; D025141:Drug Resistance, Fungal; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage* / Q000009:adverse effects; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000401:mortality; D006801:Humans; D015994:Incidence; D017964:Itraconazole / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D017964:Itraconazole; D015725:Fluconazole