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Previous Volume 356:348-359 January 25, 2007 Number 4 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set CME Exam Supplementary Material Editorial by De Pauw, B. E. 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 neutropenia resulting from chemotherapy for acute myelogenous leukemia or the myelodysplastic syndrome are at high risk for difficult-to-treat and often fatal invasive fungal infections.

Methods In this randomized, multicenter study involving evaluators who were unaware of treatment assignments, we compared the efficacy and safety of posaconazole with those of fluconazole or itraconazole as prophylaxis for patients with prolonged neutropenia. Patients received prophylaxis with each cycle of chemotherapy until recovery from neutropenia and complete remission, until occurrence of an invasive fungal infection, or for up to 12 weeks, whichever came first. We compared the incidence of proven or probable invasive fungal infections during treatment (the primary end point) between the posaconazole and fluconazole or itraconazole groups; death from any cause and time to death were secondary end points.

Results A total of 304 patients were randomly assigned to receive posaconazole, and 298 patients were randomly assigned to receive fluconazole (240) or itraconazole (58). Proven or probable invasive fungal infections were reported in 7 patients (2%) in the posaconazole group and 25 patients (8%) in the fluconazole or itraconazole group (absolute reduction in the posaconazole group, –6%; 95% confidence interval, –9.7 to –2.5%; P<0.001), fulfilling statistical criteria for superiority. Significantly fewer patients in the posaconazole group had invasive aspergillosis (2 [1%] vs. 20 [7%], P<0.001). Survival was significantly longer among recipients of posaconazole than among recipients of fluconazole or itraconazole (P=0.04). Serious adverse events possibly or probably related to treatment were reported by 19 patients (6%) in the posaconazole group and 6 patients (2%) in the fluconazole or itraconazole group (P=0.01). The most common treatment-related adverse events in both groups were gastrointestinal tract disturbances.

Conclusions In patients undergoing chemotherapy for acute myelogenous leukemia or the myelodysplastic syndrome, posaconazole prevented invasive fungal infections more effectively than did either fluconazole or itraconazole and improved overall survival. There were more serious adverse events possibly or probably related to treatment in the posaconazole group. (ClinicalTrials.gov number, NCT00044486 [ClinicalTrials.gov] .)

Source Information

From the University of Cologne, Cologne, Germany (O.A.C.); University Hospital Gasthuisberg, Leuven, Belgium (J.M.); University of California, Los Angeles, (D.J.W.); Duke University Medical Center, Durham, NC (J.P.); University of Mainz, Mainz, Germany (A.J.U.); National Cancer Institute, Bethesda, MD (T.J.W.); Weill Cornell Medical College, New York (D.H.); Silesian Medical University, Katowice, Poland (J.H.); Sahlgrenska University Hospital, Göteborg, Sweden (D.S.); Singapore General Hospital, Singapore, Singapore (Y.-T.G.); University of Pisa, Pisa, Italy (M.P.); and Schering-Plough Research Institute, Kenilworth, NJ (C.H., R.S., D.A.-G.).

Address reprint requests to Dr. Cornely at the Klinik I für Innere Medizin, Klinikum der Universität zu Köln, 50924 Cologne, Germany, or at oliver.cornely{at}uni-koeln.de.

Full Text of this Article

Related Letters:

Posaconazole Prophylaxis in Hematologic Cancer
Weiler S., Bellmann R., Kontoyiannis D. P., Lewis R. E., Krause D. S., van Nieuwkoop C., van Dissel J. T., Ullmann A. J., Chandrasekar P., Patino H., Cornely O. A., Ullmann A. J., Hardalo C.
Extract | Full Text | PDF  
N Engl J Med 2007; 356:2214-2218, May 24, 2007. Correspondence

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