title: Efficacy of caspofungin as salvage therapy for invasive aspergillosis compared to standard therapy in a historical cohort.
abstract: In a non-comparative study, caspofungin was effective salvage therapy for approximately half of the patients refractory to or intolerant of standard antifungal agents for invasive aspergillosis. To establish a frame of reference for these results, we compared the response to caspofungin with responses to other antifungal agents in a historical cohort of similar patients. The efficacy could be evaluated in 83 patients who received caspofungin 50 mg daily after a 70-mg loading dose. The historical control group, identified through a retrospective review of medical records, included 214 evaluable patients possibly refractory to or intolerant of ≥1 week of standard antifungal therapy. All patients had documented invasive aspergillosis. Favorable response was defined as a complete or partial response to therapy. Underlying diseases, baseline neutropenia, corticosteroid use, and sites of infection were similar in both studies. Most patients had received amphotericin B formulations and/or itraconazole, and were refractory to standard therapy. Favorable response rates were 45% with caspofungin and 16% with standard therapy. The unadjusted odds ratio for a favorable response (caspofungin/standard therapy) was 4.1 (95% confidence interval: 2.2, 7.5). After adjusting for potential imbalances in the frequency of disseminated infection, neutropenia, steroid use, and bone marrow transplantation between groups, the odds ratio remained at 4.1 (2.1, 7.9). Although only tentative conclusions about relative efficacy can be drawn from retrospective comparisons, caspofungin appeared to be at least as efficacious as an amphotericin B formulation and/or itraconazole for the treatment of invasive aspergillosis in patients refractory to or intolerant of their initial antifungal therapy.
authors: Division of Hematology/Oncology, University of Florida College of Medicine, P.O. Box 100278, Gainesville, FL, 32610-0278, USA. john.hiemenz@medicine.ufl.edu
authors: J W
authors: JW
authors: Hiemenz
authors: I I
authors: II
authors: Raad
authors: J A
authors: JA
authors: Maertens
authors: R Y
authors: RY
authors: Hachem
authors: A J
authors: AJ
authors: Saah
authors: C A
authors: CA
authors: Sable
authors: J A
authors: JA
authors: Chodakewitz
authors: M E
authors: ME
authors: Severino
authors: P
authors: P
authors: Saddier
authors: R S
authors: RS
authors: Berman
authors: D M
authors: DM
authors: Ryan
authors: M J
authors: MJ
authors: Dinubile
authors: T F
authors: TF
authors: Patterson
authors: D W
authors: DW
authors: Denning
authors: T J
authors: TJ
authors: Walsh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage / Q000627:therapeutic use; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy* / Q000382:microbiology; D001230:Aspergillus / Q000187:drug effects; D000077336:Caspofungin; D025141:Drug Resistance, Fungal; D054714:Echinocandins / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D055744:Invasive Pulmonary Aspergillosis / Q000188:drug therapy* / Q000382:microbiology; D017964:Itraconazole / Q000008:administration & dosage / Q000627:therapeutic use; D055666:Lipopeptides; D008297:Male; D008875:Middle Aged; D009503:Neutropenia; D011379:Prognosis; D016879:Salvage Therapy; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D017964:Itraconazole; D000666:Amphotericin B; D000077336:Caspofungin