Background: Voriconazole is an investigational antifungal agent with a good safety profile with fungicidal activity against Aspergillus Methods: Protocol 150-604 was an open label, noncomparative, phase III trial of voriconazole for salvage treatment of invasive fungal infections including aspergillosis. The study was conducted at > 60 sites in the US and Canada from 9/9712/99. Definite (invasive) aspergillosis was confirmed by a positive culture or evidence of tissue invasion from a biopsy sample. In subjects with allo BMT or prolonged neutropenia, probable aspergillosis was supported by a positive culture or cytology from a BAL sample. Subjects were treated with intravenous and/or oral voriconazole for up to 12 weeks. Global response at end of treatment was assessed by the investigator as complete, partial, stable or failure compared to baseline. Results: As of May, 1999, 51 subjects with aspergillosis who failed treatment with other antifungals were recruited. Antifungal treatment including lipid formulations of ampho B, was given for at least 5 days prior to entry. Most subjects had hematological conditions or malignancies, often with allo BMT, GVHD, prolonged neutropenia, or relapsed malignancy. Diagnosis of aspergillosis was confirmed as definite in 73%, probable in 27%. Sites of infection were: pulmonary (51 % ), sinus (20'/0), skin/subcutaneous (12 % ), and cerebral (6%). Satisfactory response rate (complete or partial) at end of treatment was 41%. Median survival on treatment was 57 days (1-196). There were 20 deaths, with 7 occurring within the first week of treatment. Six subjects discontinued voriconazole because of AE s or lab abnormalities. AE s reported by > l0% of all subjects treated with voriconazole in protocol 604 included: abnormal vision, rash, headache, fever, sepsis, hypotension, nausea, vomiting, diarrhea, peripheral edema, respiratory disorder, and urinary tract infection. Conclusion: Based on the results of this open-label trial, voriconazole is potentially beneficial for the treatment of invasive aspergillosis in patients with hematological malignancies and conditions who have failed other treatments including lipid formulations of ampho B.
Full conference title:
- IDSA 38th