Objectives: Efficacy and safety of posaconazole (POS), an extended-spectrum triazole, as prophylaxis for invasive fungal infections (IFIs) were evaluated in 2 large, randomised, active-controlled, parallel-group trials. The trials were conducted in 2 populations at high risk for IFI: allogeneic haematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) and neutropenic patients undergoing intensive chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). Methods: In study 1, HSCT recipients with GVHD received either oral POS 200 mg three times daily or oral fluconazole (FLU) 400 mg once daily for up to 16 weeks. In study 2, patients with newly diagnosed or first relapse of AML or MDS received oral POS 200 mg three times daily or oral standard azole [FLU 400 mg once daily or itraconazole (ITZ) solution 200 mg twice daily] with each cycle of chemotherapy until complete remission or for up to 12 weeks. The incidence of proven or probable IFI was the main endpoint in each study. IFI incidence was evaluated 7 days after the last dose of study drug and at predetermined times (ie, 112 and 100 days after randomization for studies 1 and 2, respectively). IFI diagnoses were adjudicated by blinded expert panels using EORTC/MSG criteria. Results: In study 1,600 patients were enrolled: 301 POS and 299 FLU. In study 2,602 patients were enrolled: 304 POS and 298 standard azole (240 FLU, 58 ITZ). In both studies, fewer IFIs occurred with POS; for almost all endpoints, the difference was significant (Table). Safety and tolerability between treatment arms were comparable within each study. In study 1, the 3 most common treatment-related adverse events (AEs) were nausea (7% vs. 9%), vomiting (4% vs. 5%), and diarrhoea (3% vs. 4%) in the POS and FLU groups, respectively. In study 2, the 3 most common treatment-related AEs were also nausea (7% vs. 8%), diarrhoea (7% vs. 7%), and vomiting (5% vs. 7%) in the POS and FLU/ITZ groups, respectively. Incidence of treatment-related AEs resulting in discontinuation was similar between POS and comparator therapy in both studies (3% for each arm in study 1; 7% vs. 6%, respectively, in study 2). Conclusion: These findings show POS is superior to standard azole therapy (FLU or ITZ) in preventing aspergillosis and other IFIs in HSCT recipients with GVHD and in AML and MDS patients with chemotherapeutic-induced neutropenia. Safety and tolerability of POS were comparable to standard azole therapy.
Full conference title:
16th European Congress of Clinical Microbiology and Infectious Diseases
- ECCMID 16th (2006)