A Multicenter, Randomized, Open-Label Study to Evaluate Safety and Efficacy of Posaconazole Vs Fluconazole in the Prophylaxis of Invasive Fungal Infection in a Chinese Population

Invasive fungal infection (IFI) is a common and fatal complication in neutropenic patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

In this multicenter, randomized study, we enrolled patients with persistent neutropenia resulting from chemotherapy for the treatment of AML and MDS. Prophylaxis with either posaconazole or fluconazole was given to the patients to compare the efficacy and safety of the 2 drugs. The treatment was given with each cycle of chemotherapy until the patient recovered from neutropenia and had complete remission, an IFI occurred, or until the patient had received a maximum of 12 weeks of treatment. The primary end point was the incidence of possible, proven, or probable diagnosis of IFI during the treatment phase in *the 2 groups; clinical failure rate, all-cause mortality, and time to first systemic antifungal treatment were secondary end points.

A total of 252 patients were included in this study, and 7 patients were excluded due to withdrawal of informed consent or deviation of eligible criteria. Finally, 124 patients from the posaconazole group and 121 patients from the fluconazole group were included; and 234 patients (117 in each group) entered into statistical analysis, respectively. The incidence of proven, probable, and possible IFI was 9.4% (11/117) and 22.2% (26/117) in the posaconazole and fluconazole groups, respectively (P = 0.0114). The clinical failure rate was lower in the posaconazole group (31.6% [95% CI: 23.3–40.9], 37/117) than in the fluconazole group (41.88% [95% CI: 32.8–51.4], 49/117); however, statistical significance was not reached (P = 0.168). The patients receiving posaconazole had a later onset of first systematic antifungal therapy than those receiving fluconazole (P = 0.0139). The most common clinical adverse reactions were liver function abnormalities, with 11 cases (9.4%) in the posaconazole group and 6 cases (5.1%) in the fluconazole group (P = 0.221).

Posaconazole demonstrates efficacy as prophylaxis against IFI in high-risk neutropenic patients with AML and MDS undergoing chemotherapy and is well tolerated during long-term use. (ClinicalTrials.gov number, NCT00811928)

No relevant conflicts of interest to declare.