Anidulafungin (Eraxis) As Effective As Fluconazole (Diflucan)

CAMDEN, N.J., June 14 -- In a head-to-head trial, anidulafungin (Eraxis) was at least as effective in treating invasive candidiasis as fluconazole (Diflucan), researchers here said.
The industry-sponsored randomized trial also found that adverse events were similar after treatment with the two drugs, according to Annette C. Reboli, M.D., of the University of Medicine and Dentistry of New Jersey, and colleagues.
A successful outcome was seen in 75.6% of the patients in the anidulafungin group, compared with 60.2% of the patients in the fluconazole group, they reported in the June 14 issue of the New England Journal of Medicine.
Although the percentage difference was high enough to suggest that the anidulafungin actually led to a significantly better response rate (at P=0.01), the finding should be treated "cautiously," the researchers said.
For one thing, they said, removing the study site with the highest enrollment reduced the difference in response, implying that there may be heterogeneity in the treatment effects. Also, they said, the robustness of the findings may be limited by the small size of the sample -- 245 patients.
The result will be "disappointing to those who sought a clear winner," said Jack Sobel, M.D., and Sanjay Revankar, M.D., both of Wayne State University School of Medicine in Detroit.
Drs. Sobel and Revankar, writing in an accompanying editorial, noted that there is a "paucity of data" comparing the new echinocandins and the azole drugs, specifically fluconazole.
What data there are, they said, form "absolutely no justification for abandoning fluconazole, given its safety, overall efficacy, and low cost." The prices of the echincocandins remain "several-fold higher" than generic fluconazole, they said.
In the study by Dr. Reboli and colleagues, patients with invasive candidiasis were randomized to intravenous treatment with either anidulafungin or fluconazole for 10 days, followed by oral fluconazole if needed.
The primary end point was both a clinical response and a microbiological response at the end of intravenous therapy and a successful outcome was achieved in 96 of 127 anidulafungin patients and in 71 of 118 fluconazole patients.
However, one of the 47 participating sites enrolled 25 patients -- or 10% of the intent-to-treat population -- and saw a 93.3% response to anidulafungin, compared to a 50% response to fluconazole.
When the data from that site was removed, Dr. Reboli and colleagues said, anidulafungin was no longer significantly better than fluconazole, although it remained non-inferior.
Their study is the first of two in the journal that deals with the treatment of Candida species. In a placebo-controlled randomized trial, Italian researchers found that prophylactic fluconazole reduced the incidence of invasive Candida infection in low-birth-weight babies.
Paolo Manzoni, M.D., of Sant'Anna Hospital in Turin, Italy, and colleagues of randomized 322 babies whose weight at birth was less than 1,500 grams to get either a placebo or fluconazole at either three or six milligrams per kilogram of bodyweight.
Treatment was continued for 30 days from birth or 45 days in the case of infants born weighing less than 1,000 grams.
The researchers found:
In the fluconazole group, only 9.8% of the infants getting six milligrams and 7.7% of those getting three milligrams were colonized by Candida, compared with 29.2% in the placebo group. The difference was significant at P<0.001 for both groups versus placebo. Of those in the placebo group, 13.2% had invasive fungal infection, compared with 2.7% in the six-milligram group and 3.8% in the three-milligram group. The differences were significant at P=0.005 and P=0.02, respectively. On the other hand, the use of the drug did not alter the progression from colonization to subsequent invasive disease, the researchers said. Mortality was similar in both groups. The study confirms previous work, according to editorialists Drs. Sobel and Revankar, and will probably not result in a change to the standard "wait and see and treat early" approach now used in neonatal intensive care units.

Primary source: New England Journal of MedicineSource reference: Manzoni P et al. "A Multicenter, Randomized Trial of Prophylactic Fluconazole in Preterm Neonates." N Engl J Med 2007;356:2483-95. Additional source: New England Journal of MedicineSource reference: Reboli AC et al. "Anidulafungin versus Fluconazole for Invasive Candidiasis." N Engl J Med 2007;356:2472-82. Additional source: New England Journal of MedicineSource reference: Sobel JD and Revankar SG. "Echinocandins -- First-Choice or First-Line Therapy for Invasive Candidiasis?" N Engl J Med 2007;356:2525-26.