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.

Abstract

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.

• Authors: M Boogaerts, D J Winston, E J Bow, G Garber, A C Reboli, A P Schwarer, N Novitzky, A Boehme, E Chwetzoff, K De Beule, Itraconazole Neutropenia Study Group
• Journal: Annals of internal medicine (Ann Intern Med) Vol. 135 Issue 6 Pg. 412-22 (Sep 18 2001) ISSN: 0003-4819 [Print] United States
• PMID: 11560454 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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