Background: Invasive fungal infection (IFI) is still the important problem causing substantial morbidity and mortality in patients with hematologic malignancy who develop neutropenia after receiving chemotherapy. To reduce the incidence of IFI, primary antifungal prophylaxis is recommended in many standard guidelines. However, there has been no randomized controlled study comparing voriconazole and placebo for primary antifungal prophylaxis in the patients with acute myeloid leukemia (AML) after receiving chemotherapy.
Material/methods: A prospective randomized controlled evaluator-blinded study was carried out to determine the efficacy and safety of voriconazole, in comparison with the placebo for primary antifungal prophylaxis in the patients with AML who had received chemotherapy for either induction or consolidation. All patients were randomly assigned in a block randomization of 1: 1 ratio. The primary endpoint was the incidence of proven or probable IFI during the hospital stay and within 30 days after receiving chemotherapy in the modified intention to treat population.
Results: A total of 40 patients with 44 courses of chemotherapy were enrolled: 22 in the voriconazole group and 22 in the placebo group. The incidence of proven or probable IFI was observed in 0 (0%) and 7 (18.18%) patients in the voriconazole and placebo group (absolute risk reduction 18.18, 95% confidence interval 0.01 to 0.36, P=0.036), respectively. The estimation of 6 patients would be needed to be treated with voriconazole, in comparison with placebo, in order to prevent 1 IFI. The mortality rate was 0% and 9% in the voriconazole and placebo group, respectively (95% confidence interval - 0.04 to 0.22, P=0.148). The median length of hospital stay was 32 (interquartile range 26, 36) and 28 (interquartile range 13, 38) days in the voriconazole and placebo group, respectively (P=0.510). Adverse events likely associated with the treatment was noted in 5 (23%) and 1 (4.5%) patients in the voriconazole and placebo group, respectively (P=0.049). The most common treatment-associated adverse effects were skin rash (2 patients, 9%) in the voriconazole group. No patients discontinued voriconazole treatment due to adverse effects.
Conclusions: Voriconazole was more effective than placebo in prevention of IFI in the patients with AML who developed neutropenia after receiving chemotherapy for induction or consolidation. There was no serious adverse effect associated with voriconazole prophylaxis
Figure: Kaplan Meier graph fig1. Time and Invasive fungal infection (Proven and Probable) fig2. Time and mortality rate