title: Application of the 2008 definitions for invasive fungal diseases to the trial comparing voriconazole versus amphotericin B for therapy of invasive aspergillosis: a collaborative study of the Mycoses Study Group (MSG 05) and the European Organization for Research and Treatment of Cancer Infectious Diseases Group.
abstract: BACKGROUND
  Strict definition of invasive aspergillosis (IA) cases is required to allow precise conclusions about the efficacy of antifungal therapy. The Global Comparative Aspergillus Study (GCAS) compared voriconazole to amphotericin B (AmB) deoxycholate for the primary therapy of IA. Because predefined definitions used for this trial were substantially different from the consensus definitions proposed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group in 2008, we recategorized the 379 episodes of the GCAS according to the later definitions.
  
  
  METHODS
  The objectives were to assess the impact of the current definitions on the classification of the episodes and to provide comparative efficacy for probable/proven and possible IA in patients treated with either voriconazole or AmB. In addition to original data, we integrated the results of baseline galactomannan serum levels obtained from 249 (65.7%) frozen samples. The original response assessment was accepted unchanged.
  
  
  RESULTS
  Recategorization allowed 59 proven, 178 probable, and 106 possible IA cases to be identified. A higher favorable 12-week response rate was obtained with voriconazole (54.7%) than with AmB (29.9%) (P < .0001). Survival was higher for voriconazole for mycologically documented (probable/proven) IA (70.2%) than with AmB (54.9%) (P = .010). Higher response rates were obtained in possible IA treated with voriconazole vs AmB with the same magnitude of difference (26.2%; 95% confidence interval [CI], 7.2%-45.3%) as in mycologically documented episodes (24.3%; 95% CI, 11.9%-36.7%), suggesting that possible cases are true IA.
  
  
  CONCLUSIONS
  Recategorization resulted in a better identification of the episodes and confirmed the higher efficacy of voriconazole over AmB deoxycholate in mycologically documented IA.
authors.affiliation: Department of Oncology and Hematology, Hôpital de Hautepierre and Université de Strasbourg, France.
authors.forename: Raoul
authors.initials: R
authors.lastname: Herbrecht
authors.affiliation: University of Texas Health Science Center and South Texas Veterans Health Care System, San Antonio.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Patterson
authors.affiliation: Peter MacCallum Cancer Center and University of Melbourne, Australia.
authors.forename: Monica A
authors.initials: MA
authors.lastname: Slavin
authors.affiliation: Infectious Diseases Service, Department of Medicine, Lausanne University Hospital (CHUV), Switzerland.
authors.forename: Oscar
authors.initials: O
authors.lastname: Marchetti
authors.affiliation: Universitaire Ziekenhuizen Leuven, Campus Gasthuisberg, KU Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Maertens
authors.affiliation: Public Health England Mycology Reference Laboratory and National Collection of Pathogenic Fungi, Bristol, United Kingdom.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Johnson
authors.affiliation: Pfizer Global Research and Development, New York, New York.
authors.forename: Haran T
authors.initials: HT
authors.lastname: Schlamm
authors.affiliation: Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: J Peter
authors.initials: JP
authors.lastname: Donnelly
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Pappas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use*; D002648:Child; D005260:Female; D006801:Humans; D055744:Invasive Pulmonary Aspergillosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D065819:Voriconazole / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B; D065819:Voriconazole
keywords: allogeneic hematopoietic stem cell transplantation; amphotericin B; neutropenia; preemptive therapy; voriconazole