Intravenous itraconazole for prophylaxis of systemic fungal infections in patients with acute myelogenous leukemia and high-risk myelodysplastic syndrome undergoing induction chemotherapy

Cancer. 2004 Feb 1;100(3):568-73. doi: 10.1002/cncr.11930.

Abstract

Background: Systemic fungal infections remain the leading cause of mortality in patients with newly diagnosed acute myelogenous leukemia (AML) and high-risk myelodysplastic syndrome (MDS). The objective of the current study was to determine whether intravenous itraconazole (i.v. ITRA) reduced the incidence of probable/proven fungal infections in this group of patients, and compare the results with those of a historic control group treated with fluconazole plus itraconazole capsules (F+I).

Methods: Patients with AML and high-risk MDS who underwent induction chemotherapy received 200 mg of i.v. itraconazole over 60 minutes every 12 hours during the first 2 days followed by 200 mg given i.v. once daily.

Results: One hundred patients were enrolled, 96 of whom were evaluable. Approximately 48% of the patients in the group of patients treated with i.v. ITRA as well as in the F+I group completed prophylaxis. Nine patients (9%) in the study group developed either proven/probable fungal infections (Candida glabrata in 5 patients, C. tropicalis in 1 patient, C krusei in 1 patient, and Fusarium in 2 patients) compared with 3 patients (4%) with proven fungal infection in the historic control group (C. tropicalis in 1 patient and Aspergillus in 2 patients). There were no significant differences noted between the two groups with regard to the percentage of patients who developed proven/probable or possible fungal infection as well as with regard to survival. These results also were obtained after adjusting for relevant prognostic factors (creatinine and bilirubin). The most common toxicity encountered with the use of i.v. ITRA was NCI Grade 3-4 hyperbilirubinemia (6%).

Conclusions: Despite its theoretic advantages, the authors found no evidence that i.v. ITRA is superior to itraconazole capsules, at least when the latter is combined with fluconazole.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Fungemia / drug therapy
  • Fungemia / prevention & control*
  • Humans
  • Infusions, Intravenous
  • Itraconazole / administration & dosage*
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / mortality
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myelodysplastic Syndromes / diagnosis
  • Myelodysplastic Syndromes / drug therapy*
  • Myelodysplastic Syndromes / mortality
  • Primary Prevention / methods
  • Probability
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Remission Induction
  • Risk Assessment
  • Survival Analysis
  • Treatment Outcome

Substances

  • Itraconazole