title: Salvage therapy with voriconazole for invasive fungal infections in patients failing or intolerant to standard antifungal therapy.
abstract: BACKGROUND
  Invasive fungal infections (IFI), particularly those caused by Aspergillus and other angioinvasive molds, are associated with an excessive mortality despite therapy.
  
  
  METHODS
  Voriconazole was prescribed on a compassionate basis to patients with IFI who were intolerant to or who had progressed despite standard therapy. Outcome was determined by protocol-based criteria as established by the consensus definitions (complete response [CR], partial response [PR], stable disease, failure, and intolerance).
  
  
  RESULTS
  Forty-five patients were enrolled in a compassionate release program (29 [64%] because of failure of response to standard therapy), between 1998 and 2002. Of the 45 patients enrolled, 35 (78%) had invasive Aspergillus, 3 (7%) had Fusarium, and 2 (4%) had Scedosporium infections. Underlying illnesses were as follows: 13 (29%) solid-organ transplant (SOT), 11 (24%) BMT, and 7 (13%) hematologic malignancy. Site of infection was as follows: 26 (58%) pulmonary, 9 (20%) disseminated, 5 (11%) central nervous system (CNS), and 3 (7%) sinus. Overall response rates were as follows: 9 (20%) CR, 17 (38%) PR, 15 (33%) failure, and 4 (9%) intolerant. Seven of the eight (88%) patients with sinus or CNS disease demonstrated stabilization of the IFI. The median duration of voriconazole therapy was 79 days with 9 (20%) patients receiving over 1 year of therapy. Nine thousand one hundred twenty-eight days of therapy were given with only four serious adverse events in two cases considered possibly or probably drug related.
  
  
  CONCLUSIONS
  In this population of severely immunocompromised patients with life-threatening IFI who have failed or were intolerant to standard antifungal therapy, voriconazole demonstrated substantial efficacy and an acceptable level of toxicity.
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA 02215, USA. lbaden@partners.org
authors.forename: L R
authors.initials: LR
authors.lastname: Baden
authors.forename: J T
authors.initials: JT
authors.lastname: Katz
authors.forename: J A
authors.initials: JA
authors.lastname: Fishman
authors.forename: C
authors.initials: C
authors.lastname: Koziol
authors.forename: A
authors.initials: A
authors.lastname: DelVecchio
authors.forename: M
authors.initials: M
authors.lastname: Doran
authors.forename: R H
authors.initials: RH
authors.lastname: Rubin
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002648:Child; D025141:Drug Resistance, Fungal; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications; D006801:Humans; D016867:Immunocompromised Host; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy* / Q000209:etiology; D009369:Neoplasms / Q000150:complications; D011743:Pyrimidines / Q000627:therapeutic use*; D016879:Salvage Therapy / Q000379:methods*; D014180:Transplantation / Q000009:adverse effects; D017211:Treatment Failure; D014230:Triazoles / Q000627:therapeutic use*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole