Posaconazole vs. fluconazole as invasive fungal infection prophylaxis in China: a multicenter, randomized, open-label study.

Abstract

BACKGROUND:

Invasive fungal infection (IFI) is common in neutropenic patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). Posaconazole is a broad-spectrum triazole antifungal drug with efficacy in prevention of IFI; however, it has not been previously studied as prophylaxis in a Chinese population.

METHODS:

This multicenter, randomized study in China enrolled AML and MDS patients with persistent chemotherapy-induced neutropenia. Prophylaxis with posaconazole or fluconazole was administered for a maximum of 12 weeks, or until patients recovered from neutropenia and achieved complete remission or an IFI occurred. The primary endpoint was incidence of proven, probable, or possible IFI during treatment. Clinical failure rate, all-cause mortality and time to first systemic antifungal treatment were secondary endpoints.

RESULTS:

Patients were randomized to receive posaconazole (n = 129) or fluconazole (n = 123); 117 patients in each group were included in the statistical analysis. The incidence of proven, probable or 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 numerically lower in the posaconazole group (37/117 (31.6%; 95%CI: 23.3 - 40.9)) than in the fluconazole group (49/117 (41.88%; 95% CI: 32.8 - 51.4)) (p = 0.168). Patients receiving posaconazole had a later onset of first systematic antifungal treatment than those receiving fluconazole (p = 0.0139). The most common important adverse events were liver function abnormalities (11 patients (8.8%) on posaconazole and 6 (5.0%) on fluconazole (p = 0.221)).

CONCLUSIONS:

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

• Authors: Yang Shen, Xiao-Jun Huang, Jian-Xiang Wang, Jie Jin, Jian-Da Hu, Kang Yu, De-Pei Wu, Shu-Jie Wang, Li Yu, Xie-Qun Chen, Ting Liu, Ying-Ming Liang, Fang-Ping Chen, Yan Li, Zhi-Xiang Shen
• Journal: International journal of clinical pharmacology and therapeutics (Int J Clin Pharmacol Ther) Vol. 51 Issue 9 Pg. 738-45 (Sep 2013) ISSN: 0946-1965 [Print] Germany
• PMID: 23924680 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antifungal Agents
• Triazoles
• posaconazole
• Fluconazole

Topics

• Adolescent
• Adult
• Aged
• Antifungal Agents (therapeutic use)
• Female
• Fluconazole (adverse effects, therapeutic use)
• Humans
• Male
• Middle Aged
• Mycoses (prevention & control)
• Prospective Studies
• Triazoles (adverse effects, therapeutic use)