Efficacy and Safety Profile of Voriconazole as Salvage Therapy for Invasive Aspergillosis with Hematologic Diseases in Korea

Background: Invasive aspergillosis (IA) is associated with significant morbidity and mortality in patients with hematologic malignancies. We investigated the efficacy and safety of voriconazole (VCZ) when used as salvage therapy for IA in Korean adults with hematologic malignancies who had not responded to prior antifungal therapy. Materials and Methods: We retrospectively reviewed data, collected from January 2007 to October 2008, from patients with proven or probable cases of IA. All were probable IA cases, except for one proven case. All cases were refractory or intolerant to antifungal therapy prior to administration of VCZ. Efficacy and safety were assessed in patients treated with VCZ for more than 3 days and for more than one dose, respectively. A favorable response [complete (CR) or partial (PR)] was defined by significant improvement of all clinical symptoms, signs, and radiologic abnormalities. Results: Fifty patients who met the inclusion criteria were enrolled. There were 27 male and 23 female patients with mean age of 44.4 years (range, 15-65 years). Underlying diseases were acute leukemia (35 cases), chronic myelogenous leukemia (4 cases), myelodysplastic syndrome (3 cases), lymphoma (3 cases) and other hematologic diseases (5 cases). Twenty-two patients had received chemotherapy and 13 patients had undergone hematopoietic stem cell transplantation. The lung was the main infection site (94%) followed by the sinus (6%). Amphotericin B deoxycholate alone was the most frequent previous antifungal therapy. The mean duration of antifungal therapy prior to VCZ therapy was 13.9 +/- 8.8 days (2-44 days). The median duration of VCZ therapy was 19 days (interquartile range, 49 days). Sixteen patients (32.0%) showed favorable responses (CR: PR=8: 8) at the end of VCZ therapy. The numbers of patients with stable disease, progression and death were, 6 (12%), 6 (12%) and 22 (44%) respectively. Most of those with unfavorable responses had relapsed underlying malignancies or refractory graft versus host diseases. Twelve patients developed drugrelated adverse events but only one patient stopped VCZ treatment prematurely. Conclusions: VCZ demonstrated an acceptable level of toxicity in patients with hematologic malignancies but further studies are required to prove its efficacy as salvage therapy.