Document 0319
 DOCN  M9490319
 TI    NIAID Mycoses Study Group Multicenter Trial of Oral Itraconazole Therapy
       for Invasive Aspergillosis.
 DT    9411
 AU    Denning DW; Lee JY; Hostetler JS; Pappas P; Kauffman CA; Dewsnup DH;
       Galgiani JN; Graybill JR; Sugar AM; Catanzaro A; et al; Department of
       Medicine, Santa Clara Valley Medical Center, San; Jose, California
       95128.
 SO    Am J Med. 1994 Aug;97(2):135-44. Unique Identifier : AIDSLINE
       MED/94337780
 AB    BACKGROUND: Invasive aspergillosis is the most common invasive mould
       infection 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.
       METHODS: A multicenter open study with strict entry criteria for
       invasive aspergillosis evaluated oral itraconazole (600 mg/d for 4 days
       followed by 400 mg/d) in patients with various underlying conditions.
       Response was based on clinical and radiologic criteria plus
       microbiology, histopathology, and autopsy data. Responses were
       categorized as complete, partial, or stable. Failure was categorized as
       an itraconazole failure or overall failure. RESULTS: Our study
       population consisted of 76 evaluable patients. Therapy duration varied
       from 0.3 to 97 weeks (median 46). At the end of treatment, 30 (39%)
       patients had a complete or partial response, and 3 (4%) had a stable
       response, and in 20 patients (26%), 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 other reasons including
       possible toxicity (7%) and death due to another cause but without
       resolution of aspergillosis (20%). Itraconazole failure rates varied
       widely according to site of disease and underlying disease group: 14%
       for pulmonary and tracheobronchial disease, 50% for sinus disease, 63%
       for central nervous system disease, and 44% for other sites; 7% in solid
       organ transplant, 29% in allogeneic bone marrow transplant patients, and
       14% in those with prolonged granulocytopenia (median 19 days), 44% in
       AIDS patients, and 32% in other host groups. The relapse rates among
       those who completed therapy and those who discontinued 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 apparently
       comparable to amphotericin B. Relapse in immunocompromised patients may
       be a problem. Controlled trials are necessary to fully assess the role
       of itraconazole in the treatment of invasive aspergillosis.
 DE    Administration, Oral  Agranulocytosis/DRUG THERAPY/MICROBIOLOGY
       Aspergillosis/*DRUG THERAPY  AIDS-Related Opportunistic Infections/DRUG
       THERAPY/MICROBIOLOGY  Central Nervous System Diseases/DRUG
       THERAPY/MICROBIOLOGY  Chi-Square Distribution  Female  Human
       Itraconazole/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/*THERAPEUTIC  USE
       Male  Middle Age  Organ Transplantation  Recurrence  Respiratory Tract
       Infections/DRUG THERAPY/MICROBIOLOGY  Support, Non-U.S. Gov't  Support,
       U.S. Gov't, P.H.S.  Treatment Outcome  CLINICAL TRIAL  JOURNAL ARTICLE
       MULTICENTER STUDY

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).