FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

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

	Full Text PDF PDA Full Text PowerPoint Slide Set 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

This article has been cited by other articles:

• Krishna, G., Ma, L., Vickery, D., Yu, X., Wu, I., Power, E., Beresford, E., Komjathy, S. (2009). Effect of Varying Amounts of a Liquid Nutritional Supplement on the Pharmacokinetics of Posaconazole in Healthy Volunteers. Antimicrob. Agents Chemother. 53: 4749-4752 [Abstract] [Full Text]  
• Harnicar, S., Adel, N., Jurcic, J. (2009). Modification of vincristine dosing during concomitant azole therapy in adult acute lymphoblastic leukemia patients. J Oncol Pharm Pract 15: 175-182 [Abstract]  
• Maschmeyer, G., Neuburger, S., Fritz, L., Bohme, A., Penack, O., Schwerdtfeger, R., Buchheidt, D., Ludwig, W.-D., on behalf of the Infectious Diseases Working Party, (2009). A prospective, randomised study on the use of well-fitting masks for prevention of invasive aspergillosis in high-risk patients. Ann Oncol 20: 1560-1564 [Abstract] [Full Text]  
• Portugal, R. D., Garnica, M., Nucci, M. (2009). Index to Predict Invasive Mold Infection in High-Risk Neutropenic Patients Based on the Area Over the Neutrophil Curve. JCO 27: 3849-3854 [Abstract] [Full Text]  
• Kolve, H., Ahlke, E., Fegeler, W., Ritter, J., Jurgens, H., Groll, A. H. (2009). Safety, tolerance and outcome of treatment with liposomal amphotericin B in paediatric patients with cancer or undergoing haematopoietic stem cell transplantation. J Antimicrob Chemother 64: 383-387 [Abstract] [Full Text]  
• Michallet, M., Ito, J. I. (2009). Approaches to the Management of Invasive Fungal Infections in Hematologic Malignancy and Hematopoietic Cell Transplantation. JCO 27: 3398-3409 [Abstract] [Full Text]  
• Dodds Ashley, E. S., Varkey, J. B., Krishna, G., Vickery, D., Ma, L., Yu, X., Malavade, D., Goodwin, M., Perfect, J. R., Power, E. (2009). Pharmacokinetics of Posaconazole Administered Orally or by Nasogastric Tube in Healthy Volunteers. Antimicrob. Agents Chemother. 53: 2960-2964 [Abstract] [Full Text]  
• Zarember, K. A., Cruz, A. R., Huang, C.-Y., Gallin, J. I. (2009). Antifungal Activities of Natural and Synthetic Iron Chelators Alone and in Combination with Azole and Polyene Antibiotics against Aspergillus fumigatus. Antimicrob. Agents Chemother. 53: 2654-2656 [Abstract] [Full Text]  
• Thompson, G. R. III, Rinaldi, M. G., Pennick, G., Dorsey, S. A., Patterson, T. F., Lewis, J. S. II (2009). Posaconazole Therapeutic Drug Monitoring: a Reference Laboratory Experience. Antimicrob. Agents Chemother. 53: 2223-2224 [Full Text]  
• Maschmeyer, G. (2009). Prevention of mould infections. J Antimicrob Chemother 63: i27-i30 [Abstract] [Full Text]  
• Segal, B. H. (2009). Aspergillosis. NEJM 360: 1870-1884 [Full Text]  
• Krishna, G., Moton, A., Ma, L., Medlock, M. M., McLeod, J. (2009). Pharmacokinetics and Absorption of Posaconazole Oral Suspension under Various Gastric Conditions in Healthy Volunteers. Antimicrob. Agents Chemother. 53: 958-966 [Abstract] [Full Text]  
• Morris, M. I. (2009). Posaconazole: A new oral antifungal agent with an expanded spectrum of activity. Am J Health Syst Pharm 66: 225-236 [Abstract] [Full Text]  
• Conte, J. E. Jr., Golden, J. A., Krishna, G., McIver, M., Little, E., Zurlinden, E. (2009). Intrapulmonary Pharmacokinetics and Pharmacodynamics of Posaconazole at Steady State in Healthy Subjects. Antimicrob. Agents Chemother. 53: 703-707 [Abstract] [Full Text]  
• Hlava, N., Niemann, C. U., Gropper, M. A., Melcher, M. L. (2009). Analytic Reviews: Postoperative Infectious Complications of Abdominal Solid Organ Transplantation. J Intensive Care Med 24: 3-17 [Abstract]  
• Barnes, R A, White, P L, Bygrave, C, Evans, N, Healy, B, Kell, J (2009). Clinical impact of enhanced diagnosis of invasive fungal disease in high-risk haematology and stem cell transplant patients. J. Clin. Pathol. 62: 64-69 [Abstract] [Full Text]  
• Cornely, O. A., Bohme, A., Buchheidt, D., Einsele, H., Heinz, W. J., Karthaus, M., Krause, S. W., Kruger, W., Maschmeyer, G., Penack, O., Ritter, J., Ruhnke, M., Sandherr, M., Sieniawski, M., Vehreschild, J.-J., Wolf, H.-H., Ullmann, A. J. (2009). Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology. haematol 94: 113-122 [Abstract] [Full Text]  
• Collins, C. D., Ellis, J. J., Kaul, D. R. (2008). Comparative cost-effectiveness of posaconazole versus fluconazole or itraconazole prophylaxis in patients with prolonged neutropenia. Am J Health Syst Pharm 65: 2237-2243 [Abstract] [Full Text]  
• Ruping, M. J. G. T., Albermann, N., Ebinger, F., Burckhardt, I., Beisel, C., Muller, C., Vehreschild, J. J., Kochanek, M., Fatkenheuer, G., Bangard, C., Ullmann, A. J., Herr, W., Kolbe, K., Hallek, M., Cornely, O. A. (2008). Posaconazole concentrations in the central nervous system. J Antimicrob Chemother 62: 1468-1470 [Full Text]  
• Kishel, J. J, Sivik, J. (2008). Breakthrough invasive fungal infection in an immunocompromised host while on posaconazole prophylaxis: an omission in patient counseling and follow-up. J Oncol Pharm Pract 14: 189-193 [Abstract]  
• Ayari, S., Gastinne, T., Guillaume, T., Chevallier, P. Sr., le Gouill, S., Blin, N., Ma, X. Sr., Brissot, E., Harousseau, j. L., Moreau, P., Moreau, P., Mohty, M. Sr., Delaunay, J. (2008). Posaconazole as Prophylaxis in Immunocompromised Patients: A Single Center Experience. ASH ANNUAL MEETING ABSTRACTS 112: 4841-4841 [Abstract]  
• Pagano, L., Fianchi, L., Caira, M. (2008). Pulmonary aspergillosis in hematologic malignancies: lights and shadows. haematol 93: 1611-1616 [Full Text]  
• Rachwalski, E. J, Wieczorkiewicz, J. T, Scheetz, M. H (2008). Posaconazole: An Oral Triazole with an Extended Spectrum of Activity. The Annals of Pharmacotherapy 42: 1429-1438 [Abstract] [Full Text]  
• Lamaris, G. A., Ben-Ami, R., Lewis, R. E., Kontoyiannis, D. P. (2008). Does pre-exposure of Aspergillus fumigatus to voriconazole or posaconazole in vitro affect its virulence and the in vivo activity of subsequent posaconazole or voriconazole, respectively? A study in a fly model of aspergillosis. J Antimicrob Chemother 62: 539-542 [Abstract] [Full Text]  
• LONGWORTH, D. L. (2008). Update in infectious disease treatment. Cleveland Clinic Journal of Medicine 75: 584-590 [Abstract] [Full Text]  
• Spreghini, E., Maida, C. M., Tomassetti, S., Orlando, F., Giannini, D., Milici, M. E., Scalise, G., Barchiesi, F. (2008). Posaconazole against Candida glabrata Isolates with Various Susceptibilities to Fluconazole. Antimicrob. Agents Chemother. 52: 1929-1933 [Abstract] [Full Text]  
• Chowdhry, R., Marshall, W. L. (2008). Analytical Reviews: Antifungal Therapies in the Intensive Care Unit. J Intensive Care Med 23: 151-158 [Abstract]  
• Penack, O., Rempf, P., Graf, B., Blau, I. W., Thiel, E. (2008). Aspergillus galactomannan testing in patients with long-term neutropenia: implications for clinical management. Ann Oncol 19: 984-989 [Abstract] [Full Text]  
• Cornely, O. A., Bohme, A., Reichert, D., Reuter, S., Maschmeyer, G., Maertens, J., Buchheidt, D., Paluszewska, M., Arenz, D., Bethe, U., Effelsberg, J., Lovenich, H., Sieniawski, M., Haas, A., Einsele, H., Eimermacher, H., Martino, R., Silling, G., Hahn, M., Wacker, S., Ullmann, A. J., Karthaus, M., on behalf of The Multinational Case Registry of th, (2008). Risk factors for breakthrough invasive fungal infection during secondary prophylaxis. J Antimicrob Chemother 61: 939-946 [Abstract] [Full Text]  
• Varga, J., Houbraken, J., Van Der Lee, H. A. L., Verweij, P. E., Samson, R. A. (2008). Aspergillus calidoustus sp. nov., Causative Agent of Human Infections Previously Assigned to Aspergillus ustus. Eukaryot Cell 7: 630-638 [Abstract] [Full Text]  
• Dungarwalla, M., Evans, S. O., Riley, U., Catovsky, D., Dearden, C. E., Matutes, E. (2008). High dose methylprednisolone and rituximab is an effective therapy in advanced refractory chronic lymphocytic leukemia resistant to fludarabine therapy. haematol 93: 475-476 [Abstract] [Full Text]  
• Spreghini, E., Maida, C. M., Milici, M. E., Scalise, G., Barchiesi, F. (2008). Posaconazole Activity against Candida glabrata after Exposure to Caspofungin or Amphotericin B. Antimicrob. Agents Chemother. 52: 513-517 [Abstract] [Full Text]  
• Pfaller, M. A., Messer, S. A., Boyken, L., Tendolkar, S., Hollis, R. J., Diekema, D. J. (2008). Selection of a Surrogate Agent (Fluconazole or Voriconazole) for Initial Susceptibility Testing of Posaconazole against Candida spp.: Results from a Global Antifungal Surveillance Program. J. Clin. Microbiol. 46: 551-559 [Abstract] [Full Text]  
• Barnes, R. A. (2008). Early diagnosis of fungal infection in immunocompromised patients. J Antimicrob Chemother 61: i3-i6 [Abstract] [Full Text]  
• Rogers, T. R. (2008). Treatment of zygomycosis: current and new options. J Antimicrob Chemother 61: i35-i40 [Abstract] [Full Text]  
• Robenshtok, E., Gafter-Gvili, A., Goldberg, E., Weinberger, M., Yeshurun, M., Leibovici, L., Paul, M. (2007). Antifungal Prophylaxis in Cancer Patients After Chemotherapy or Hematopoietic Stem-Cell Transplantation: Systematic Review and Meta-Analysis. JCO 25: 5471-5489 [Abstract] [Full Text]  
• Bulpa, P., Dive, A., Sibille, Y. (2007). Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. Eur Respir J 30: 782-800 [Abstract] [Full Text]  
• 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. (2007). Posaconazole Prophylaxis in Hematologic Cancer. NEJM 356: 2214-2218 [Full Text]  
• Smith, P. J., Olson, J. A., Constable, D., Schwartz, J., Proffitt, R. T., Adler-Moore, J. P. (2007). Effects of dosing regimen on accumulation, retention and prophylactic efficacy of liposomal amphotericin B. J Antimicrob Chemother 59: 941-951 [Abstract] [Full Text]  
• De Pauw, B. E., Donnelly, J. P. (2007). Prophylaxis and Aspergillosis -- Has the Principle Been Proven?. NEJM 356: 409-411 [Full Text]  
• (2007). Posaconazole Superior to Fluconazole for Preventing Aspergillosis. JWatch Infect. Diseases 2007: 1-1 [Full Text]