Efficacy and Safety Profile of Caspofungin as a Salvage Therapy for Invasive Fungal Infections in Korean Patients with Hematologic Diseases

Choi, Su Mi; Park, Sun Hee; Lee, Dong Gun; Choi, Jung Hyun; Yoo, Jin Hong; Min, Woo Sung; Shin, Wan Shik; Kim, Chun Choo

Abstract

BACKGROUND: Invasive fungal infection (IFI) is an important cause of morbidity and mortality in patients with hematologic malignancy. Patients with IFI who fail to standard therapy have poor prognoses. We investigated the efficacy and safety of caspofungin (CAS) in Korean adults with hematologic diseases and IFI who did not respond to the conventional antifungal therapy.
MATERIALS AND METHODS
Patients with IFI refractory or intolerant to standard antifungal therapy received CAS 50 mg IV daily after 70 mg loading dose on day 1. Efficacy and safety of CAS were assessed in patients who received more than one dose. Favorable response [complete (CR) or partial (PR)] was defined as significant improvement of all clinical symptoms, signs, and radiologic abnormalities.
RESULTS
From Feb. 2004 to Feb. 2005, 55 patients who met the inclusion criteria were enrolled. There were 32 male and 23 female patients with mean age of 38.2 years (range, 16-65). Underlying diseases were acute leukemia (33 cases), myelodysplastic syndrome (12 cases), chronic myelogenous leukemia (3 cases), and other hematologic diseases (7 cases). Thirty-six patients were receiving chemotherapy and 13 patients were under hematopoietic stem cell transplantation (HSCT). The number of proven, probable, possible, and indeterminate IFI cases was 1, 5, 47, and 2, respectively. Conventional amphotericin B, intravenous itraconazole, and liposomal amphotericin B were administered for average of 14.9 days prior to administering CAS. Mean duration of CAS therapy was 12.8 days (range, 1-45). Twenty-three patients (41.8%) showed favorable responses (CR:PR=8:15) at the end of CAS therapy. Chemotherapy group, neutropenic state, remitted state of underlying disease, and no steroid therapy were significant prognostic factors for favorable response. Eight (14.5%) patients developed drug-related adverse events such as fever, skin eruption, and hepatic dysfunction which were reversible after discontinuation of CAS. Drug-related nephrotoxicity was not observed.
CONCLUSION
On the basis of our investigation, CAS was effective and safe as a salvage therapy of refractory IFI or as an alternative for patients intolerant to standard antifungal agents.