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Previous Volume 351:1391-1402 September 30, 2004 Number 14 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by Klastersky, J. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background Patients with persistent fever and neutropenia often receive empirical therapy with conventional or liposomal amphotericin B for the prevention and early treatment of invasive fungal infections. Caspofungin, a member of the new echinocandin class of compounds, may be an effective alternative that is better tolerated than amphotericin B.

Methods In this randomized, double-blind, multinational trial, we assessed the efficacy and safety of caspofungin as compared with liposomal amphotericin B as empirical antifungal therapy. At study entry, patients were stratified according to risk and according to whether they had previously received antifungal prophylaxis. A successful outcome was defined as the fulfillment of all components of a five-part composite end point.

Results Efficacy was evaluated in 1095 patients (556 receiving caspofungin and 539 receiving liposomal amphotericin B). After adjustment for strata, the overall success rates were 33.9 percent for caspofungin and 33.7 percent for liposomal amphotericin B (95.2 percent confidence interval for the difference, –5.6 to 6.0 percent), fulfilling statistical criteria for the noninferiority of caspofungin. Among patients with baseline fungal infections, a higher proportion of those treated with caspofungin had a successful outcome (51.9 percent vs. 25.9 percent, P=0.04). The proportion of patients who survived at least seven days after therapy was greater in the caspofungin group (92.6 percent vs. 89.2 percent, P=0.05). Premature study discontinuation occurred less often in the caspofungin group than in the amphotericin B group (10.3 percent vs. 14.5 percent, P=0.03). The rates of breakthrough fungal infections and resolution of fever during neutropenia were similar in the two groups. Fewer patients who received caspofungin sustained a nephrotoxic effect (2.6 percent vs. 11.5 percent, P<0.001), an infusion-related event (35.1 percent vs. 51.6 percent, P<0.001), or a drug-related adverse event or discontinued therapy because of drug-related adverse events.

Conclusions Caspofungin is as effective as and generally better tolerated than liposomal amphotericin B when given as empirical antifungal therapy in patients with persistent fever and neutropenia.

Source Information

From the National Cancer Institute, National Institutes of Health, Bethesda, Md. (T.J.W.); Merck Research Laboratories, West Point, Pa. (H.T., M.R.B., R.J.L., C.A.S.); University of Virginia Health System, Charlottesville (G.R.D.); Universitaire Ziekenhuizen Leuven, Leuven, Belgium (J.A.M.); Brigham and Women's Hospital and Dana–Farber Cancer Institute — both in Boston (L.R.B.); Clinical Hospital No. 4, Lublin, Poland (A.D.); Klinikum der Universität zu Köln, Cologne, Germany (O.A.C.); and University Hospital St. Radboud, Nijmegen, the Netherlands (B.E.P.).

Address reprint requests to Dr. Walsh at the National Cancer Institute, Bldg. 10, Rm. 13N-240, 10 Center Dr., Bethesda, MD 20892.

Full Text of this Article

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Caspofungin versus Liposomal Amphotericin B for Empirical Therapy
Kontoyiannis D. P., Lewis R. E., Tattevin P., Bareau B., Camus C., Marty F. M., Lowry C. M., Schneemann M., Imhof A., Danaher P. J., Jones B. L., McLintock L. A., Walsh T. J., Donowitz G. R., dePauw B. E.
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N Engl J Med 2005; 352:410-414, Jan 27, 2005. Correspondence

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