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Safety, plasma concentrations, and efficacy of high-dose fluconazole in invasive mold infections
E J Anaissie1, D P Kontoyiannis, C Huls
1Department of Medical Specialties, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Abstract:
A trial of the antifungal triazole fluconazole was conducted in cancer patients with presumed or proven mold infection. Groups of patients received fluconazole at four dosages (800, 1200, 1600, or 2000 mg/day). Adverse events, plasma levels, and clinical response were examined. Thirty-nine patients were enrolled. The 28 evaluable patients had presumed (13 patients) or proven (15) mold infection with Aspergillus (4) and Fusarium (3) species, Zygomycetes organisms (1), or nonspeciated mold (7). Adverse effects included elevated liver function test results (8 patients), nausea and vomiting (2), and erythema multiforme (1). Neurologic toxicity occurred in 3 patients receiving 2000 mg/day. Average steady-state peak plasma concentrations were 51.8, 74.4, and 91.8 mg/L for dosages 1200, 1600, and 2000 mg/day, respectively. Seven of 28 evaluable patients responded. Response did not appear to be related to dose. Fluconazole is well tolerated at total daily doses up to 1600 mg. The data suggest a linear plasma concentration-dose relationship. The activity of fluconazole in refractory mold infections seems to be limited.
Insights
This study evaluated fluconazole (an antifungal) in cancer patients with mold infections. Fluconazole showed limited effectiveness in refractory cases but was well-tolerated up to 1600 mg/day.
Area of Science:
- Mycology
- Clinical Pharmacology
- Oncology
Background:
- Mold infections pose a significant threat to immunocompromised cancer patients.
- Antifungal therapies are crucial for managing these infections.
- The efficacy and safety of fluconazole in treating mold infections require further investigation.
Purpose of the Study:
- To assess the safety, plasma levels, and clinical response of fluconazole in cancer patients with presumed or proven mold infections.
- To determine the relationship between fluconazole dosage, plasma concentration, and patient outcomes.
- To evaluate fluconazole's potential role in treating refractory mold infections.
Main Methods:
- A clinical trial involving 39 cancer patients with mold infections.
- Patients received fluconazole at dosages of 800, 1200, 1600, or 2000 mg/day.
- Adverse events, plasma concentrations, and clinical responses were monitored.
Main Results:
- Seven out of 28 evaluable patients showed a response to fluconazole, with no clear dose-response relationship observed.
- Elevated liver function tests were the most common adverse event (8 patients).
- Neurologic toxicity was observed in 3 patients receiving the highest dose (2000 mg/day).
- A linear relationship between fluconazole plasma concentration and dosage was suggested.
- Fluconazole was generally well-tolerated up to 1600 mg/day.
Conclusions:
- Fluconazole demonstrates limited activity against refractory mold infections in cancer patients.
- The antifungal triazole fluconazole is well-tolerated at daily doses up to 1600 mg.
- Higher doses (2000 mg/day) may be associated with increased toxicity.