| Background
Patients with neutropenia resulting from cytotoxic chemotherapy for acute myelogenous leukaemia or myelodysplastic syndrome are at high risk for invasive fungal infections. These infections are difficult to treat and often fatal.
Methods
This randomized, evaluator-blinded, multicentre study compared the efficacy and safety of posaconazole with that of standard azoles (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 or up to 12 weeks. Incidences of invasive fungal infections during treatment were compared, and 95 percent confidence intervals for the difference (posaconazole-standard azoles) were computed. All-cause mortality and time to death were secondary end points.
Results
The intention-to-treat population comprised 602 patients: 304 randomized to posaconazole, 298 randomized to standard azoles (240 fluconazole, 58 itraconazole). The incidences of proven and probable invasive fungal infections were 7 (2 percent) in the posaconazole group and 25 (8 percent) in the standard azoles group (95 percent confidence interval, –9.68 percent to –2.5 percent, P<0.001), fulfilling statistical criteria for superiority. Aspergillus was the most common pathogen. Significantly fewer cases of invasive aspergillosis occurred with posaconazole prophylaxis (2 [1 percent] vs. 20 [7 percent]; P<0.001). Survival was significantly greater in 3 recipients of posaconazole (P=0.035). Safety and tolerability of posaconazole were comparable to that of fluconazole.
Conclusions
Posaconazole is more effective than standard azoles in preventing invasive fungal infections in high-risk neutropenic patients. Posaconazole is well tolerated and improved overall survival rate in patients undergoing remission induction chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome.
This trial is registered at the National Library of Medicine with identifier NCT00044486.
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