title: Caspofungin as salvage monotherapy for invasive aspergillosis in patients with haematological malignancies or following allogeneic stem cell transplantation: efficacy and concomitant cyclosporin A.
abstract: Caspofungin (CAS) has shown efficacy as salvage monotherapy for invasive aspergillosis (IA) in two open label non-comparative trials. The association between hepatotoxicity and concomitant use of CAS and cyclosporin A (CsA) has not been fully elucidated. We report results on CAS efficacy in the first cohort from outside Europe and USA and the interaction between CAS and CsA. We retrospectively reviewed the charts of all patients with haematological malignancies or postallogeneic haematopoietic stem cell transplant (HSCT) who received >/=1 dose of CAS as salvage monotherapy for IA as part of the Australian Special Access Scheme (4/2001-8/2002). Outcomes were assessed at the end of CAS therapy. Favourable response (FR) was defined as >50% clinical and radiological improvement. Risk factors for elevation of liver transaminases (LTs) were examined using multivariate models. 54 patients were included in the analysis with 47 neutropenic at study entry. Proven or probable IA occurred in 11 and refractory IA in 28. An FR occurred in 26 (48.1%) and predictors for a poor response to CAS were allogeneic HSCT, graft vs. host disease and treatment with CAS for <14 days. Concomitant CAS and CsA for >7 days was an independent risk factor for laboratory hepatoxicity. The CAS efficacy results from the Australian cohort confirm those of previous studies. Close monitoring of LTs is necessary on concomitant CAS and CsA but clinically relevant hepatotoxicity is rare.
authors: Infectious Diseases Unit, Alfred Hospital, Melbourne, Vic, Australia. o.morrissey@alfred.org.au
authors: C O
authors: CO
authors: Morrissey
authors: M A
authors: MA
authors: Slavin
authors: M A
authors: MA
authors: O'Reilly
authors: J R
authors: JR
authors: Daffy
authors: J F
authors: JF
authors: Seymour
authors: A P
authors: AP
authors: Schwarer
authors: J
authors: J
authors: Szer
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy* / Q000209:etiology; D000077336:Caspofungin; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D054714:Echinocandins / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D019337:Hematologic Neoplasms / Q000382:microbiology* / Q000628:therapy; D006801:Humans; D055666:Lipopeptides; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects*; D012189:Retrospective Studies; D016879:Salvage Therapy; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D016572:Cyclosporine; D000077336:Caspofungin