title: Multicenter, noncomparative study of caspofungin in combination with other antifungals as salvage therapy in adults with invasive aspergillosis.
abstract: BACKGROUND
  Caspofungin inhibits synthesis of beta-1,3-glucan, an essential component of the Aspergillus cell wall. This echinocandin has demonstrated efficacy (45% success) as salvage monotherapy of invasive aspergillosis (IA). Interest remains as to whether caspofungin, in combination with other antifungal classes, can improve the efficacy against IA.
  
  
  METHODS
  The study involved 53 adults with documented IA who were refractory to or intolerant of standard antifungal therapy and received caspofungin and 1 other mold-active antifungal agent (at the investigator's discretion). Efficacy was assessed by signs, symptoms, and radiographs at the end of combination therapy and Day 84 after combination therapy initiation. Favorable (complete or partial) responses required significant clinical and radiographic improvement. Diagnoses and outcomes were assessed by an independent expert.
  
  
  RESULTS
  Among the 53 patients enrolled the most common underlying diseases were acute leukemia (53%), lymphoma (11%), and chronic leukemia (6%). Pulmonary aspergillosis (81%) was the most common site, and most patients (87%) were refractory to prior therapy. Success at the end of combination therapy and Day 84 was 55% (29/53) and 49% (25/51), respectively. Fifty-seven percent of patients with neutropenia and 54% who received an allogeneic hematopoietic stem cell transplant responded favorably. Survival at Day 84 was 55%. Combination therapy, dosed on average for 31.3 days, was well tolerated. Two (4%) serious drug-related adverse events, both attributed to voriconazole, occurred. None of the patients discontinued caspofungin due to toxicity.
  
  
  CONCLUSIONS
  Caspofungin in combination with a triazole or polyene was an effective alternative as salvage therapy for patients with recalcitrant Aspergillus infections.
authors.affiliation: Department of Hematology, University Hospital Gasthuisberg, Leuven, Belgium. johan.maertens@uz.kuleuven.ac.be
authors.forename: Johan
authors.initials: J
authors.lastname: Maertens
authors.forename: Axel
authors.initials: A
authors.lastname: Glasmacher
authors.forename: Raoul
authors.initials: R
authors.lastname: Herbrecht
authors.forename: Anne
authors.initials: A
authors.lastname: Thiebaut
authors.forename: Catherine
authors.initials: C
authors.lastname: Cordonnier
authors.forename: Brahm H
authors.initials: BH
authors.lastname: Segal
authors.forename: John
authors.initials: J
authors.lastname: Killar
authors.forename: Arlene
authors.initials: A
authors.lastname: Taylor
authors.forename: Nicholas
authors.initials: N
authors.lastname: Kartsonis
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Patterson
authors.forename: Michael
authors.initials: M
authors.lastname: Aoun
authors.forename: Denis
authors.initials: D
authors.lastname: Caillot
authors.forename: Carole
authors.initials: C
authors.lastname: Sable
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy* / Q000401:mortality; D000077336:Caspofungin; D004359:Drug Therapy, Combination; D054714:Echinocandins; D005260:Female; D006801:Humans; D055666:Lipopeptides; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D016879:Salvage Therapy; D017211:Treatment Failure
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D010456:Peptides, Cyclic; D000077336:Caspofungin