Cordonnier, C., Rovira, M., Maertens, J., Olavarria, E., Faucher, C., Bilger, K., . . . Infectious Diseases Working Party, European Group for Blood and Marrow Transplantation. (2010). Voriconazole for secondary prophylaxis of invasive fungal infections in allogeneic stem cell transplant recipients: results of the VOSIFI study. Haematologica, 95, 1762–1768.

To determine if voriconazole is a safe and effective antifungal prophylactic agent to be used for stem cell transplant (SCT) recipients.

All patients in the study received voriconazole prophylactically in one of two ways: either intravenously with maintenance doses of 4 mg/kg every 12 hours after receiving a loading dose of 6 mg/kg every 12 hours for two doses only or 200 mg of oral voriconazole every 12 hours after receiving a loading dose of 400 mg every 12 hours for two doses only. Loading doses were administered 48 hours after completion of conditioning chemotherapy for SCT and at least three days prior to SCT. Prophylactic voriconazole was to be continued up to 100 days posttransplant and could be continued for other specific medical conditions warranting additional coverage. The efficacy of prophylactic voriconazole was assessed during screening, baseline, and regular intervals during the study, which included posttransplant follow-ups.

• Forty-five adult patients (62% male, 38% female) were included.
• Age ranged from 22 to 72 years.
• Key disease characteristics were patients undergoing allogeneic SCT that included a conditioning regimen for any variety of hematological diseases.
• Patients had a proven or suspected history of invasive fungal infection in the prior 12 months.
   

• Multi-site  
• The study was conducted at 17 European healthcare sites, including locations in Belgium, France, Germany, Portugal, Spain, Sweden, Switzerland, and the United Kingdom.

Patients were undergoing the active treatment phase of care.

This study was a phase III, prospective, open-label, multicenter trial.

• Proportion of patients who developed a proven or probable invasive fungal infection between starting prophylaxis and the 12-month posttransplant follow-up evaluation 
• Proportion of patients who developed a proven or probable invasive fungal infection between the start of prophylaxis and the end of prophylaxis or the 6-month posttransplant follow-up evaluation 
• Time for a proven or probable invasive fungal infection to occur after initiation of prophylaxis
• Proportion of patients on prophylaxis who were free from a proven or probable invasive fungal infection 12 months posttransplant

Three of 42 patients who were given prophylactic voriconazole developed invasive fungal infections within six months of transplant (two were proven to be reoccurrences of old fungal infections and one was a probable new case).

In regard to the safety of voriconazole, the most common adverse events related to treatment included

• Hepatotoxicity in four patients
• Headache in three patients
• Visual hallucinations in three patients.

Other adverse events that were reported in the population were

• Mucosal inflammation
• Diarrhea
• Vomiting
• Pyrexia
• Headache
• Graft-versus-host disease
• Hypertension
• Febrile neutropenia
• Thrombocytopenia
• Abdominal pain
• Anemia
• Insomnia
• Nausea
• Rash.

Strictly based on this study, it appears as though voriconazole is safe and effective in the prevention of newly developing or reoccurring invasive fungal infection in patients undergoing SCT.

Small sample (<100)

Adherence to antifungal prophylactic regimens in SCT recipients is imperative to them achieving survival without developing invasive fungal disease. Study findings suggest that prophylaxis with antifungals for 100 days post SCT appears safe and may be of benefit in the prevention of invasive fungal infections in this population.