Intravenous and oral itraconazole versus intravenous amphotericin B deoxycholate as empirical antifungal therapy for persistent fever in neutropenic patients with cancer who are receiving broad-spectrum antibacterial therapy. A randomized, controlled trial

Ann Intern Med. 2001 Sep 18;135(6):412-22. doi: 10.7326/0003-4819-135-6-200109180-00010.


Background: Amphotericin B deoxycholate is currently the standard empirical antifungal therapy in neutropenic patients with cancer who have persistent fever that does not respond to antibiotic therapy. However, this treatment often causes infusion-related and metabolic toxicities, which may be dose limiting.

Objective: To compare the efficacy and safety of itraconazole with those of amphotericin B as empirical antifungal therapy.

Design: An open randomized, controlled, multicenter trial, powered for equivalence.

Setting: 60 oncology centers in 10 countries.

Patients: 384 neutropenic patients with cancer who had persistent fever that did not respond to antibiotic therapy.

Intervention: Intravenous amphotericin B or intravenous itraconazole followed by oral itraconazole solution.

Measurements: Defervescence, breakthrough fungal infection, drug-related adverse events, and death.

Results: For itraconazole and amphotericin B, the median duration of therapy was 8.5 and 7 days and the median time to defervescence was 7 and 6 days, respectively. The intention-to-treat efficacy analysis of data from 360 patients showed response rates of 47% and 38% for itraconazole and amphotericin B, respectively (difference, 9.0 percentage points [95% CI, -0.8 to 19.5 percentage points]). Fewer drug-related adverse events occurred in the itraconazole group than the amphotericin B group (5% vs. 54% of patients; P = 0.001), and the rate of withdrawal because of toxicity was significantly lower with itraconazole (19% vs. 38%; P = 0.001). Significantly more amphotericin B recipients had nephrotoxicity (P < 0.001). Breakthrough fungal infections (5 patients in each group) and mortality rates (19 deaths in the itraconazole group and 25 deaths in the amphotericin B group) were similar. Sixty-five patients switched to oral itraconazole solution after receiving the intravenous formulation for a median of 9 days.

Conclusions: Itraconazole and amphotericin B have at least equivalent efficacy as empirical antifungal therapy in neutropenic patients with cancer. However, itraconazole is associated with significantly less toxicity.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Amphotericin B / administration & dosage*
  • Amphotericin B / adverse effects
  • Anti-Bacterial Agents / therapeutic use
  • Antifungal Agents / administration & dosage*
  • Antifungal Agents / adverse effects
  • Antineoplastic Agents / adverse effects
  • Deoxycholic Acid / administration & dosage*
  • Deoxycholic Acid / adverse effects
  • Drug Combinations
  • Fever / etiology
  • Humans
  • Infusions, Intravenous
  • Itraconazole / administration & dosage*
  • Itraconazole / adverse effects
  • Mycoses / complications
  • Mycoses / drug therapy*
  • Neoplasms / complications*
  • Neoplasms / drug therapy
  • Neutropenia / immunology*
  • Opportunistic Infections / complications
  • Opportunistic Infections / drug therapy*
  • Risk Factors
  • Treatment Failure


  • Anti-Bacterial Agents
  • Antifungal Agents
  • Antineoplastic Agents
  • Drug Combinations
  • Deoxycholic Acid
  • Itraconazole
  • Amphotericin B
  • amphotericin B, deoxycholate drug combination