title: High-dose caspofungin as a component of combination antifungal therapy in 91 patients with neoplastic diseases and hematopoietic stem cell transplantation: a critical review of short-term and long-term adverse events.
abstract: The antifungal activity of echinocandins is concentration dependent. Previously, we demonstrated that high-dose caspofungin (HD-CSP; 100 mg daily) was well tolerated in 34 immunosuppressed patients with cancer and may have favorably influenced outcomes. We retrospectively assessed all 91 patients in whom HD-CSP was given for the treatment of invasive fungal disease (IFD). The median number of doses was 18.5 ± 21.5, and in 8 (9%) patients more than 40 doses were given. Most (62%) of the patients had leukemia. A total of 45 (49%) patients had undergone stem cell transplantation; 80% received allogeneic grafts and 47% had graft-versus-host disease. High-dose corticosteroids were given during antifungal therapy in 26 (29%) patients. In all, 8 (9%) patients had new elevation in serum bilirubin during HD-CSP therapy; normalization occurred after voriconazole and HD-CSP were discontinued in 4 patients each. No other short-term or delayed adverse events were observed. In all, 40 (44%) patients died of IFD. High-dose corticosteroids during HD-CSP (odds ratio [OR] 8, 95% confidence interval [CI] 2.1-30.4; P < .002) and starting HD-CSP in the critical care unit (OR 67.5, 95% CI 5.25-868.9; P < .001) were associated with death from fungal disease. Prolonged HD-CSP therapy was well tolerated. Drug-induced hyperbilirubinemia may pose a potential limitation for continued HD-CSP use in highly susceptible patients with hematologic neoplasms and stem cell transplantation.
authors.affiliation: Department of Medicine, NYU Langone Medical Center, New York, NY, USA amar.safdar@nyumc.org.
authors.forename: Amar
authors.initials: A
authors.lastname: Safdar
authors.affiliation: Department of Infectious Diseases, Infection Control and Employee Health, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Gilhen
authors.initials: G
authors.lastname: Rodriguez
authors.affiliation: Department of Infectious Diseases, Infection Control and Employee Health, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Zuniga
authors.affiliation: Department of Infectious Diseases, Infection Control and Employee Health, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Fadi
authors.initials: F
authors.lastname: Al Akhrass
authors.affiliation: Department of Infectious Diseases, Infection Control and Employee Health, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Anupam
authors.initials: A
authors.lastname: Pande
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000009:adverse effects*; D001663:Bilirubin / Q000097:blood; D000077336:Caspofungin; D004359:Drug Therapy, Combination; D054714:Echinocandins / Q000009:adverse effects*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D055666:Lipopeptides; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology*; D012189:Retrospective Studies
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077336:Caspofungin; D001663:Bilirubin
keywords: corticosteroids; critical care unit; fungemia; high-dose caspofungin; immune suppression; invasive candidiasis; invasive fungal disease; leukemia; pulmonary aspergillosis; stem cell transplantation