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Caspofungin Efficacious for Empirical Use in Febrile Neutropenia

For empirical antifungal therapy in patients with persistent febrile neutropenia, caspofungin is efficacious and better tolerated than liposomal amphotericin B.

Antifungal treatment plus broad-spectrum antibiotic therapy is the standard of care for managing persistent fever and neutropenia in patients undergoing cancer chemotherapy or hematopoietic stem-cell transplantation. However, which antifungal agent to select is unclear (see, for example, Journal Watch Infectious Diseases Feb 8 2002 and Oct 4 2001). In a recent industry-supported, multinational, randomized, double-blind trial, researchers compared the use of caspofungin and liposomal amphotericin B in 1095 such patients. The primary study endpoint was a favorable response, as determined by five criteria (successful treatment of baseline fungal infections; absence of breakthrough fungal infection; survival for 7 days after completion of therapy; no premature discontinuation of assigned treatment due to drug toxicity or lack of efficacy; resolution of fever). Patients were stratified upon enrollment according to relative risk of fungal disease and previous use of systemic antifungal prophylaxis.

Analysis of the primary endpoint, adjusted for strata, showed overall favorable responses in 33.9% of caspofungin recipients and 33.7% of liposomal amphotericin B recipients. Caspofungin was significantly better than liposomal amphotericin B with respect to three of the criteria: treatment of baseline infections, survival to 7-day follow-up, and discontinuation of study medication. No significant differences were seen between the two agents in rates of breakthrough fungal infections or resolution of fever during neutropenia.

Comment: These findings support using caspofungin as a less toxic alternative to liposomal amphotericin B in patients with fever and neutropenia. As noted by an editorialist, we now need a trial comparing caspofungin and voriconazole in such patients, as well as a means to determine who is most likely to benefit from empirical antifungal therapy.

— Richard T. Ellison III, MD

Published in Journal Watch Infectious Diseases October 25, 2004

Citation(s):

Walsh TJ et al. Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med 2004 Sep 30; 351:1391-402.

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Klastersky J. Antifungal therapy in patients with fever and neutropenia -- More rational and less empirical? N Engl J Med 2004 Sep 30; 351:1445-7.

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• Medline abstract (Free)