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.
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.


METHODS
An open randomized, controlled, multicenter trial, powered for equivalence.


METHODS
60 oncology centers in 10 countries.


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


METHODS
Intravenous amphotericin B or intravenous itraconazole followed by oral itraconazole solution.


METHODS
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.
Boogaerts
M
M
Department of Hematology, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium.
Winston
D J
DJ
Bow
E J
EJ
Garber
G
G
Reboli
A C
AC
Schwarer
A P
AP
Novitzky
N
N
Boehme
A
A
Chwetzoff
E
E
De Beule
K
K
D000284:Administration, Oral; D000666:Amphotericin B / Q000008:administration & dosage* / Q000009:adverse effects; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects; D003840:Deoxycholic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D004338:Drug Combinations; D005334:Fever / Q000209:etiology; D006801:Humans; D007262:Infusions, Intravenous; D017964:Itraconazole / Q000008:administration & dosage* / Q000009:adverse effects; D009181:Mycoses / Q000150:complications / Q000188:drug therapy*; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy; D009503:Neutropenia / Q000276:immunology*; D009894:Opportunistic Infections / Q000150:complications / Q000188:drug therapy*; D012307:Risk Factors; D017211:Treatment Failure
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D004338:Drug Combinations; D003840:Deoxycholic Acid; D017964:Itraconazole; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination