Pana, Z.D., Kourti, M., Vikelouda, K., Vlahou, A., Katzilakis, N., Papageorgiou, M., . . . Roilides, E. (2018). Voriconazole antifungal prophylaxis in children with malignancies: A nationwide study. Journal of Pediatric Hematology/Oncology, 40, 22-26.

To determine the safety of voriconazole (VRC) as antifungal prophylaxis (AFP) in pediatric hematology/oncology patients.

Patients received IV VRC 5-7 mg/kg every 12 hours as AFP, not as empiric treatment. Dosing and duration of VRC therapy was at the discretion of the treating physician. Median VRC dose = 7 mg/kg. Median duration of VRC = 17 days (range = 1-31 days). Median number of AFP courses = 1.7 (range = 1-6) per patient.

• N = 249   
• AGE: Median = 6; range not specified. Inclusion criteria states ages 0-17.
• MALES: 55%      
• FEMALES: 45%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Pediatric cancer patients (any malignancy), although the majority had acute lymphoblastic leukemia, non-Hodgkin lymphoma, or acute myeloid leukemia.
• OTHER KEY SAMPLE CHARACTERISTICS: Researchers assessed risk factors for IFIs in the two weeks prior to initiation of VRC treatment. These risk factors included corticosteroid use, severity of neutropenia, grading of mucositis, type of surgery, ICU transfer, chemotherapy, and previous antibiotic therapy.

• SITE: Multi-site   
• SETTING TYPE: Inpatient    
• LOCATION: Greece

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS: Pediatrics

Retrospective chart review

Researchers assessed the rate of breakthrough IFIs during AFP and tabulated the incidence, time of onset, and severity of all AEs related to VRC.

Only one breakthrough IFI was found in the 429 courses of VRC given to 249 unique patients. Median duration of AFP with VRC was 17 days (range = 1-31 days). Median number of courses of VRC was 1.7 (range = 1-6) per patient. Females required more courses of VRC (median = 2, range = 1-4) than males (median = 1, range = 1-6) (p > 0.05). The underlying malignancy had a significant effect on the number of courses of VRC, with patients with leukemia receiving a median of 2 courses (range = 1-6). Patients without leukemia required a median of one course (range = 1-4) (odds ratio = 0.47; 95% CI [0.047, 0.5]; p = 0.019).

Seventy AEs of any grade were reported (a rate of 16.3%). There was no significant correlation between age, sex, and type of AEs. Of the 70 AEs, 38.5% were grade I, 48.4% were grade II, and 12.8% were grade III. Severity of AEs was not impacted by sex (p = 0.745), age (p = 0.78), and type of AE (p = 0.365). None of the AEs was severe enough to warrant discontinuation of VRC.

VRC provides effective prophylaxis in pediatric hematology/oncology patients at risk for IFIs. AEs were tolerable and manageable. However, the pediatric population may not be able to report subjective AEs, which could result in underdiagnosis of AEs. The risk of long-term AEs remains unknown.

Risk of bias (no control group)

Although AFP with VRC is effective, safe, and fairly well-tolerated, nurses should monitor their patients for early signs of AEs.