Itraconazole oral solution for primary prophylaxis of fungal infections inpatients with hematological malignancy and profound neutropenia: a randomized, double-blind, double-placebo, multicenter trial comparing itraconazoleand amphotericin B

Systemic and superficial fungal infections are a major problem among immuno compromised patients with hematological malignancy. A double-blind, double- placebo, randomized, multicenter trial was performed to compare the efficac y and safety of itraconazole oral solution (2.5 mg/kg of body weight twice a day) with amphotericin B capsules (500 mg orally four times a day) for pr ophylaxis of systemic and superficial fungal infection. Prophylactic treatm ent was initiated on the first day of chemotherapy and was continued until the end of the neutropenic period (>0.5 x 10(9) neutrophils/liter) or up to a maximum of 3 days following the end of neutropenia, unless a systemic fu ngal infection was documented or suspected. The maximum treatment duration was 56 days. In the intent-to-treat population, invasive aspergillosis was noted in 5 (1.8%) of the 281 patients assigned to itraconazole oral solutio n and in 9 (3.3%) of the 276 patients assigned to oral amphotericin B; of t hese, 1 and 4 patients died, respectively. Proven systemic fungal infection (including invasive aspergillosis) occurred in 8 patients (2.8%) who recei ved itraconazole, compared with 13 (4.7%) who received oral amphotericin B. Itraconazole significantly reduced the incidence of superficial fungal inf ections as compared to oral amphotericin B (2 [1%] versus 13 [5%]; P = 0.00 4), Although the incidences of suspected fungal infection (including fever of unknown origin) were not different between the groups, fewer patients we re administered intravenous systemic antifungals (mainly intravenous amphot ericin B) in the group receiving itraconazole than in the group receiving o ral amphotericin B (114 [41%] versus 132 [48%]; P = 0.066). Adequate plasma itraconazole levels were achieved in about 80% of the patients from 1 week after the start of treatment. In both groups, the trial medication was saf e and well tolerated. Prophylactic administration of itraconazole oral solu tion significantly reduces superficial fungal infection in patients with he matological malignancies and neutropenia. The incidence of proven systemic fungal infections, the number of deaths due to deep fungal infections, and the use of systemic antifungals tended to be lower in the itraconazole-trea ted group than in the amphotericin B-treated group, without statistical sig nificance. Itraconazole oral solution is a broad-spectrum systemic antifung al agent with prophylactic activity in neutropenic patients, especially for those at high risk of prolonged neutropenia.