title: Liposomal amphotericin B versus the combination of fluconazole and itraconazole as prophylaxis for invasive fungal infections during induction chemotherapy for patients with acute myelogenous leukemia and myelodysplastic syndrome.
abstract: BACKGROUND
  Fungal infections are a major cause of morbidity and mortality in patients undergoing induction chemotherapy for acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). The authors evaluated the efficacy and toxicity of liposomal amphotericin B (L-AmB) compared with a combination of fluconazole plus itraconazole (F+I) as prophylaxis in this setting.
  
  
  METHODS
  Patients with newly diagnosed AML or high-risk MDS who were undergoing initial induction chemotherapy were randomized to receive either F+I (fluconazole 200 mg orally every 12 hours plus itraconazole tablets 200 mg orally every 12 hours) or L-AmB (3 mg/kg intravenously 3 times per week) in this prospective, open-label study.
  
  
  RESULTS
  Seventy-two L-AmB-treated patients and 67 F+I-treated patients were enrolled in the study. Of these, 47% of patients completed antifungal prophylaxis without a change in therapy for proven or suspected fungal infection. Three patients in each arm developed a proven fungal infection. Twenty-three percent of the L-AmB-treated patients and 24% of the F+I-treated patients were changed to alternative antifungal therapy because of persistent fever (P value not significant). Nine percent of the L-AmB-treated patients developed pneumonia of unknown etiology compared with 16% of the F+I-treated patients (P value not significant). Increases in serum creatinine levels to > 2 mg/dL (20% for the L-AmB arm vs. 6% for the F+I arm; P = 0.012) and increases in serum bilirubin levels to > 2 mg/dL (43% vs. 22%, respectively; P = 0.021) were more common with L-AmB. Infusion-related reactions were noted in five L-AmB-treated patients. Responses to chemotherapy and induction mortality rates were similar for the two arms.
  
  
  CONCLUSIONS
  L-AmB and F+I appear similar in their efficacy as antifungal prophylaxis during induction chemotherapy for patients with AML and MDS. L-AmB was associated with higher rates of increased serum bilirubin and creatinine levels.
authors.affiliation: Department of Leukemia, the University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA. gmattizu@mdanderson.org
authors.forename: Gloria N
authors.initials: GN
authors.lastname: Mattiuzzi
authors.forename: Elihu
authors.initials: E
authors.lastname: Estey
authors.forename: Issam
authors.initials: I
authors.lastname: Raad
authors.forename: Francis
authors.initials: F
authors.lastname: Giles
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Yu
authors.initials: Y
authors.lastname: Shen
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Kontoyiannis
authors.forename: Charles
authors.initials: C
authors.lastname: Koller
authors.forename: Mark
authors.initials: M
authors.lastname: Munsell
authors.forename: Miloslav
authors.initials: M
authors.lastname: Beran
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000666:Amphotericin B / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D017964:Itraconazole / Q000008:administration & dosage / Q000627:therapeutic use*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000276:immunology; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000517:prevention & control*; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000276:immunology; D009894:Opportunistic Infections / Q000517:prevention & control*; D011446:Prospective Studies; D016019:Survival Analysis
chemical_list: D000935:Antifungal Agents; D000970:Antineoplastic Agents; D008081:Liposomes; C068538:liposomal amphotericin B; D017964:Itraconazole; D000666:Amphotericin B; D015725:Fluconazole