Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia.

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].).

• Authors: Oliver A Cornely, Johan Maertens, Drew J Winston, John Perfect, Andrew J Ullmann, Thomas J Walsh, David Helfgott, Jerzy Holowiecki, Dick Stockelberg, Yeow-Tee Goh, Mario Petrini, Cathy Hardalo, Ramachandran Suresh, David Angulo-Gonzalez
• Journal: The New England journal of medicine (N Engl J Med) Vol. 356 Issue 4 Pg. 348-59 (Jan 25 2007) ISSN: 1533-4406 [Electronic] United States
• PMID: 17251531 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2007 Massachusetts Medical Society.

Chemical References

• Antifungal Agents
• Antineoplastic Agents
• Triazoles
• Itraconazole
• posaconazole
• Fluconazole

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antifungal Agents (adverse effects, therapeutic use)
• Antineoplastic Agents (adverse effects)
• Female
• Fluconazole (adverse effects, therapeutic use)
• Humans
• Itraconazole (adverse effects, therapeutic use)
• Kaplan-Meier Estimate
• Leukemia, Myeloid, Acute (complications, drug therapy, mortality)
• Male
• Middle Aged
• Mycoses (mortality, prevention & control)
• Myelodysplastic Syndromes (complications, drug therapy, mortality)
• Neutropenia (chemically induced, drug therapy, mortality)
• Opportunistic Infections (prevention & control)
• Single-Blind Method
• Treatment Outcome
• Triazoles (adverse effects, therapeutic use)