Marc Boogaerts, MD, PhD; Drew J. Winston, MD; Eric J. Bow, MD; Gary Garber, MD; Annette C. Reboli, MD; Anthony P. Schwarer, MD, FRACP; Nicolas Novitzky, MD, PhD; Angelika Boehme, MD; Elisabeth Chwetzoff, MD; Karel De Beule, RPh; and the Itraconazole Neutropenia Study Group*
Grant Support: By Janssen Research Foundation, Beerse, Belgium.
Requests for Single Reprints: Marc Boogaerts, MD, PhD, Department of Hematology, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Boogaerts: Department of Hematology, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium.
Dr. Winston: Transplantation Biology Program, UCLA School of Medicine, Center for the Health Sciences, 10833 Le Conte Avenue, Los Angeles, CA 90095-1678.
Dr. Bow: Department of Internal Medicine, The University of Manitoba, Health Sciences Centre, 820 Sherbrooke Street, Winnipeg, Manitoba R3A 1R9, Canada.
Dr. Garber: Division of Infectious Disease, Ottawa Hospital-General Campus, University of Ottawa, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada.
Dr. Reboli: Department of Medicine, Robert Wood Johnson Medical School at Camden, Cooper Hospital, Education and Research Building, 401 Haddon Avenue, Room 270, Camden, NJ 08103.
Dr. Schwarer: Bone Marrow Transplant Programme, Alfred Hospital, Commercial Road, Melbourne, Victoria 3181, Australia.
Dr. Novitzky: Department of Haematology, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Anzio Road, Observatory, Cape Town 7925, South Africa.
Dr. Boehme: Medical Clinic III, J.W. Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany.
Dr. Chwetzoff: Bømloveien 16, 4027 Stavanger, Norway.
Dr. De Beule: Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Author Contributions: Conception and design: M. Boogaerts, D.J. Winston, E. Chwetzoff, K. De Beule.
Analysis and interpretation of the data: M. Boogaerts, D.J. Winston, E.J. Bow, G. Garber, A.P. Schwarer, N. Novitzky, K. De Beule.
Drafting of the article: M. Boogaerts, D.J. Winston, E.J. Bow, G. Garber, A.P. Schwarer, N. Novitzky, K. De Beule.
Critical revision of the article for important intellectual content: M. Boogaerts, D.J. Winston, E.J. Bow, G. Garber, A.C. Reboli, A.P. Schwarer, N. Novitzky, A. Boehme.
Final approval of the article: 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.
Provision of study materials or patients: D.J. Winston, G. Garber, A.C. Reboli, A.P. Schwarer, N. Novitzky, A. Boehme.
Statistical expertise: E.J. Bow.
Collection and assembly of data: D.J. Winston.
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.
To compare the efficacy and safety of itraconazole with those of amphotericin B as empirical antifungal therapy.
An open randomized, controlled, multicenter trial, powered for equivalence.
60 oncology centers in 10 countries.
384 neutropenic patients with cancer who had persistent fever that did not respond to antibiotic therapy.
Intravenous amphotericin B or intravenous itraconazole followed by oral itraconazole solution.
Defervescence, breakthrough fungal infection, drug-related adverse events, and death.
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.
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.
*For other members of the Itraconazole Neutropenia Study Group, see the Appendix.
Marc Boogaerts, Drew J. Winston, Eric J. Bow, Gary Garber, Annette C. Reboli, Anthony P. Schwarer, et al. 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;135:412–422. doi: 10.7326/0003-4819-135-6-200109180-00010
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Published: Ann Intern Med. 2001;135(6):412-422.
Endocrine and Metabolism, Hematology/Oncology.
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