Abstract
6735 Background: In patients with hematologic malignancies, invasive fungal infections, particularly aspergillosis, is a leading cause of infection and associated mortality. The availability of new agents with different mechanisms of action has renewed interest in developing combination strategies for these infections. In patients with acute leukemia monotherapy for invasive aspergillosis fails in many if not most cases. We recently published (Cancer 2003) our experience using combination caspofungin and liposomal amphotericin in patients with invasive fungal infections who failed monotherapy with amphotericin. Overall, 60% had a favorable response to combination antifungal therapy. Voriconazole is a new triazole antifungal approved for the treatment of invasive aspergillosis in patients who are intolerant or refractory to other agents. Since its introduction in September 2002, a group of patients with resistant fungal pneumonias have been treated with a combination of voriconazole and caspofungin. To our knowledge this abstract represents the first clinical data to be reported for combination antifungal therapy with voriconazole. Methods: We conducted a retrospective evaluation of patients with leukemia and invasive fungal infection treated with combination voriconazole and caspofungin between 9/02–7/03. Response to therapy was graded as either favorable (required both clinical and radiographic improvement) or unfavorable. Results: On preliminary analysis we have identified 27 patients (19 with AML and 8 with other leukemias). Patients received combination therapy for a median of 12 days (range 5–82 days). Survival was highly associated with response to antifungal therapy. Fourteen patients (52%) had a favorable response to combination therapy and 11 (79%) remain alive. Thirteen patients (48%) had an unfavorable response and only 1 (8%) is still alive (P=0.0003). In general unexpected toxicities were not seen. Conclusions: We conclude that combination therapy with voriconazole and caspofungin is safe in patients with leukemia and invasive fungal infections and that this combination appears to successfully salvage some patients who fail antifungal monotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer
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