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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.
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“When compared with amphotericin B deoxycholate (mean daily dose, 0.7 mg/kg), itraconazole (200 mg iv q12h for 2 days, 200 mg iv per day for 12 days, and then 400-mg solution po per day) showed similar breakthrough fungal infection rates and mortality but significantly less toxicity (A-I) [144].”
From Guidelines for Treatment of Candidiasis (2004) · cites this paper as [144]
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“Itraconazole has an adequate antifungal spectrum of activity and has been shown to have activity equivalent to that of amphotericin B [144].”
From Guidelines for Treatment of Candidiasis (2004) · cites this paper as [144]
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Metadata
- Authors
- Boogaerts, M., Winston, D. J., Bow, E. J., Garber, G., Reboli, A. C., Schwarer, A. P., Novitzky, N., Boehme, A., Chwetzoff, E., De Beule, K., & and the Itraconazole Neutropenia Study Group*
- Affiliations
- Janssen (Belgium) (BE)
- From University Hospital, Leuven, Belgium; University of California, Los Angeles, Medical Center, Los Angeles, California; University of Manitoba, Winnipeg, Manitoba, Canada; Ottawa Hospital–General Campus, University of Ottawa, Ottawa, Ontario, Canada; Robert Wood Johnson Medical School at Camden, Cooper Hospital, Camden, New Jersey; Alfred Hospital, Melbourne, Australia; Groote Schuur Hospital, Cape Town, South Africa; University Hospital, Frankfurt, Germany;
- Corresponding author
- Boogaerts, Marc
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 2001-09-18
- Volume
- 135
- Issue
- 6
- Pages
- 412-422
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- OpenAlex
- W1989277463
- Cited by
- 321
- References
- 26
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 9 · 2015: 8 · 2014: 6 · 2013: 12 · 2012: 16
- FWCI
- 20.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- Murdoch University Research Portal (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Oncology › Neutropenia and Cancer Infections
- Health Sciences › Medicine › Infectious Diseases › Fungal Infections and Studies
- Keywords
- itraconazole, amphotericin B deoxycholate, empirical antifungal therapy, persistent fever, neutropenia, cancer patients, breakthrough fungal infection, nephrotoxicity, drug toxicity, defervescence, broad-spectrum antibiotic therapy, febrile neutropenia
- MeSH terms
- Administration, Oral, Amphotericin B, Anti-Bacterial Agents, Antifungal Agents, Antineoplastic Agents, Deoxycholic Acid, Drug Combinations, Fever, Humans, Infusions, Intravenous, Mycoses, Neoplasms, Neutropenia, Opportunistic Infections, Risk Factors, Treatment Failure, Itraconazole
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- CoChat. (2026). Citation check: 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. https://app.cochat.ai/papers/10.7326/0003-4819-135-6-200109180-00010
- The paper
- Boogaerts, M., Winston, D. J., Bow, E. J., Garber, G., Reboli, A. C., Schwarer, A. P., Novitzky, N., Boehme, A., Chwetzoff, E., De Beule, K., & and the Itraconazole Neutropenia Study Group*. (2001). 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. Annals of Internal Medicine. https://doi.org/10.7326/0003-4819-135-6-200109180-00010
