Efficacy and toxicity of caspofungin in combination with liposomal amphotericin B as primary or salvage treatment of invasive aspergillosis in patients with hematologic malignancies

Abstract
BACKGROUND Caspofungin (CAS) as salvage therapy for refractory invasive aspergillosis (IA) had a response rate of 45% among a heterogeneous group of patients. The use of CAS with other agents is appealing given its unique mechanism of action. Therefore, the authors retrospectively evaluated the efficacy and toxicity of CAS plus liposomal amphotericin B (LipoAMB) in patients with documented (definite or probable) or possible IA. METHODS Patients were evaluable for outcome if they received CAS/LipoAMB for at least 7 days. Patients who received CAS and LipoAMB sequentially were excluded. All patients were evaluable for toxicity. Outcome was assessed weekly and at the end of therapy. Stable disease and progression were considered treatment failures. RESULTS Forty‐eight patients with documented (n = 23) or possible (n = 25) IA were identified between March 2001 and December 2001. The majority of the patients (65%) received CAS/LipoAMB as salvage therapy for progressive IA despite 7 or more days of previous LipoAMB monotherapy. The overall response rate was 42%. No significant toxic effects were seen. Factors associated with failure at the end of therapy were documented IA (P = 0.03), significant steroid use before the study (P = 0.02), and duration of combination therapy for less than14 days (P =0.01). The response rate in patients with progressive documented IA was low (18%). CONCLUSIONS The CAS/LipoAMB combination is a promising preemptive therapy for IA and was generally well tolerated. This combination might have limited benefit as salvage therapy for documented IA. Cancer 2003;98:292–9. © 2003 American Cancer Society. DOI 10.1002/cncr.11479