Multicenter, noncomparative study of caspofungin in combination with other antifungals as salvage therapy in adults with invasive aspergillosis

BACKGROUND: Caspofungin inhibits synthesis of beta-1,3-glucan, an essential component of the Aspergillus cell wall. This echinocandin has demonstrated efficacy (45% success) as salvage monotherapy of invasive aspergillosis (IA). Interest remains as to whether caspofungin, in combination with other antifungal classes, can improve the efficacy against IA. METHODS: The study involved 53 adults with documented IA who were refractory to or intolerant of standard antifungal therapy and received caspofungin and 1 other mold-active antifungal agent (at the investigator's discretion). Efficacy was assessed by signs, symptoms, and radiographs at the end of combination therapy and Day 84 after combination therapy initiation. Favorable (complete or partial) responses required significant clinical and radiographic improvement. Diagnoses and outcomes were assessed by an independent expert. RESULTS: Among the 53 patients enrolled the most common underlying diseases were acute leukemia (53%), lymphoma (11%), and chronic leukemia (6%). Pulmonary aspergillosis (81%) was the most common site, and most patients (87%) were refractory to prior therapy. Success at the end of combination therapy and Day 84 was 55% (29/53) and 49% (25/51), respectively. Fifty-seven percent of patients with neutropenia and 54% who received an allogeneic hematopoietic stem cell transplant responded favorably. Survival at Day 84 was 55%. Combination therapy, dosed on average for 31.3 days, was well tolerated. Two (4%) serious drug-related adverse events, both attributed to voriconazole, occurred. None of the patients discontinued caspofungin due to toxicity. CONCLUSIONS: Caspofungin in combination with a triazole or polyene was an effective alternative as salvage therapy for patients with recalcitrant Aspergillus infections.