NIAID MYCOSES STUDY-GROUP MULTICENTER TRIAL OF ORAL ITRACONAZOLE THERAPY FOR INVASIVE ASPERGILLOSIS

BACKGROUND: Invasive aspergillosis is the most common invasive mould i nfection and a major cause of mortality in immunocompromised patients. Response to amphotericin B, the only antifungal agent licensed in the United States for the treatment of aspergillosis, is suboptimal. METH ODS: A multicenter open study with strict entry criteria for invasive aspergillosis evaluated oral itraconazole (600 mg/d for 4 days followe d by 400 mg/d) in patients with various underlying conditions. Respons e was based on clinical and radiologic criteria plus microbiology, his topathology, and autopsy data. Responses were categorized as complete, partial, or stable. Failure was categorized as an itraconazole failur e or overall failure. RESULTS: Our study population consisted of 76 ev aluable patients. Therapy duration varied from 0.3 to 97 weeks (median 46). At the end of treatment, 30 (39%) patients had a complete or par tial response, and 3 (4%) had a stable response, and in 20 patients (2 6%), the protocol therapy was discontinued early (at 0.6 to 54.3 weeks ) because of a worsening clinical course or death due to aspergillosis (itraconazole failure). Twenty-three (30%) patients withdrew for othe r reasons including possible toxicity (7%) and death due to another ca use but without resolution of aspergillosis (20%). Itraconazole failur e rates varied widely according to site of disease and underlying dise ase group: 14% for pulmonary and tracheobronchial disease, 50% for sin us disease, 63% for central nervous system disease, and 44% for other sites; 7% in solid organ transplant, 29% in allogeneic bone marrow tra nsplant patients, and 14% in those with prolonged granulocytopenia (me dian 19 days), 44% in AIDS patients, and 32% in other host groups. The relapse rates among those who completed therapy and those who discont inued early for possible toxicity were 12% and 40%, respectively; all were still immunosuppressed. CONCLUSION: Oral itraconazole is a useful alternative therapy for invasive aspergillosis with response rates ap parently comparable to amphotericin B. Relapse in immunocompromised pa tients may be a problem. Controlled trials are necessary to fully asse ss the role of itraconazole in the treatment of invasive aspergillosis .