Shen, Y., Huang, X.J., Wang, J.X., Jin, J., Hu, J.D., Yu, K., . . . Shen, Z.X. (2013). Posaconazole vs. fluconazole as invasive fungal infection prophylaxis in China: A multicenter, randomized, open-label study. International Journal of Clinical Pharmacology and Therapeutics, 51, 738–745.

To compare the efficacy and safety of posaconazole and fluconazole in the prevention of invasive fungal infection (IFI) in Chinese patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) receiving chemotherapy

Patients in China with MDS or AML with persistent chemotherapy-induced neutropenia (expected to last longer than seven days) were enrolled. Posaconazole or fluconazole was administered for a maximum of 12 weeks, or until recovery from neutropenia and complete remission or until IFI was diagnosed. The endpoint was incidence of proven, probable, or possible IFI during treatment.

• N = 244  
• AGE = 18–70 years; median in posaconazole group was 40 years (range: 17–61 years), median in fluconazole was 40 years (range: 15–68 years)
• MALES: Posaconazole, 55%; fluconazole, 52%  
• FEMALES: Posaconazole, 62%; fluconazole, 65%
• KEY DISEASE CHARACTERISTICS: De novo AML (posaconazole, 56%; fluconazole, 60%; relapsed AML (posaconazole, 46%; fluconazole, 45%); MDS (posaconazole, 15%; fluconazole, 12%)
• OTHER KEY SAMPLE CHARACTERISTICS: Duration of neutropenia in posaconazole (less than two weeks, 52%; more than two weeks, 65%); in fluconazole (less than two weeks, 55%; more than two weeks, 62%)

• SITE: Multi-site   
• SETTING TYPE: Outpatient   
• LOCATION: China

• PHASE OF CARE: Active antitumor treatment

• Prospective, randomized study

• Fisher’s method was used for analyzing between-group comparison. 
• A Kaplan-Meier analysis was used to calculate time-related parameters, including the time to first onset of proven, probable, or possible IFI, and time to first use of empirical antifungal therapy (from day of randomization).
• Log-rank tests were used for comparison between groups.

Two hundred forty-five patients entered safety analysis (124 in posaconazole and 121 in fluconazole). After exclusions, 117 patients were included in each set. Incidence of IFI was 9.4% and 22.2% in the posaconazole and fluconazole groups, respectively. There was a difference in rates of -12.8% in favor of posaconazole. There was an incidence of 3.42% when only proven and probable diagnoses were considered. Noninferiority of posaconazole compared with fluconazole was established with a difference in incidence rate of -5.98%. The 100-day time to first onset of proven, probable, or possible IFI was 13.8 (SD = 3.5%) in the posaconazole group and 29.2 (SD = 4.6%) in the fluconazole/itraconazole group.

Antifungal prophylaxis has been shown to be a successful strategy in patients at high risk for IFI. Posaconazole showed significant advantage compared with fluconazole in reducing the incidence of IFI. The advantage of posaconazole in decreasing the incidence may translate into reduced need for systemic antifungal treatment.

The study raises awareness of the potential for use of posaconazole as a reasonable prophylactic medication for IFI. There is some evidence that second-generation azoles may be more effective for prophylaxis in high-risk patients.