title: Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial.
abstract: BACKGROUND
  Invasive aspergillosis is an important cause of morbidity and mortality in immunocompromised patients. Current treatments provide limited benefit. Posaconazole is an extended-spectrum triazole with in vitro and in vivo activity against Aspergillus species.
  
  
  METHODS
  We investigated the efficacy and safety of posaconazole oral suspension (800 mg/day in divided doses) as monotherapy in an open-label, multicenter study in patients with invasive aspergillosis and other mycoses who were refractory to or intolerant of conventional antifungal therapy. Data from external control cases were collected retrospectively to provide a comparative reference group.
  
  
  RESULTS
  Cases of aspergillosis deemed evaluable by a blinded data review committee included 107 posaconazole recipients and 86 control subjects (modified intent-to-treat population). The populations were similar and balanced with regard to prespecified demographic and disease variables. The overall success rate (i.e., the data review committee-assessed global response at the end of treatment) was 42% for posaconazole recipients and 26% for control subjects (odds ratio, 4.06; 95% confidence interval, 1.50-11.04; P=.006). The differences in response between the modified intent-to-treat treatment groups were preserved across additional, prespecified subsets, including infection site (pulmonary or disseminated), hematological malignancy, hematopoietic stem cell transplantation, baseline neutropenia, and reason for enrollment (patient was refractory to or intolerant of previous antifungal therapy). An exposure-response relationship was suggested by pharmacokinetic analyses.
  
  
  CONCLUSIONS
  Although the study predates extensive use of echinocandins and voriconazole, these findings demonstrate that posaconazole is an alternative to salvage therapy for patients with invasive aspergillosis who are refractory to or intolerant of previous antifungal therapy.
authors.affiliation: Immunocompromised Host Section, National Cancer Institute, Bethesda, MD 20892, USA. walsht@mail.nih.gov
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Walsh
authors.forename: Issam
authors.initials: I
authors.lastname: Raad
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Patterson
authors.forename: Pranatharthi
authors.initials: P
authors.lastname: Chandrasekar
authors.forename: Gerald R
authors.initials: GR
authors.lastname: Donowitz
authors.forename: Richard
authors.initials: R
authors.lastname: Graybill
authors.forename: Reginald E
authors.initials: RE
authors.lastname: Greene
authors.forename: Ray
authors.initials: R
authors.lastname: Hachem
authors.forename: Susan
authors.initials: S
authors.lastname: Hadley
authors.forename: Raoul
authors.initials: R
authors.lastname: Herbrecht
authors.forename: Amelia
authors.initials: A
authors.lastname: Langston
authors.forename: Arnold
authors.initials: A
authors.lastname: Louie
authors.forename: Patricia
authors.initials: P
authors.lastname: Ribaud
authors.forename: Brahm H
authors.initials: BH
authors.lastname: Segal
authors.forename: David A
authors.initials: DA
authors.lastname: Stevens
authors.forename: Jo-Anne H
authors.initials: JA
authors.lastname: van Burik
authors.forename: Charles S
authors.initials: CS
authors.lastname: White
authors.forename: Gavin
authors.initials: G
authors.lastname: Corcoran
authors.forename: Jagadish
authors.initials: J
authors.lastname: Gogate
authors.forename: Gopal
authors.initials: G
authors.lastname: Krishna
authors.forename: Lisa
authors.initials: L
authors.lastname: Pedicone
authors.forename: Catherine
authors.initials: C
authors.lastname: Hardalo
authors.forename: John R
authors.initials: JR
authors.lastname: Perfect
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy* / Q000382:microbiology; D001230:Aspergillus / Q000145:classification / Q000302:isolation & purification; D006801:Humans; D016015:Logistic Models; D016879:Salvage Therapy; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole