In this study, the efficacy data for CANCIDAS in neutropenic patients with candidemia were limited. In a separate compassionate use study, 4 patients with hepatosplenic candidiasis received prolonged therapy with CANCIDAS following other long-term antifungal therapy; three of these patients had a favorable response.
14.3 Esophageal Candidiasis (and information on oropharyngeal candidiasis)
The safety and efficacy of CANCIDAS in the treatment of esophageal candidiasis was eva luated in one large, controlled, noninferiority, clinical trial and two smaller dose-response studies.

In all 3 studies, patients were required to have symptoms and microbiological documentation of esophageal candidiasis; most patients had advanced AIDS (with CD4 counts <50/mm3).

Of the 166 patients in the large study who had culture-confirmed esophageal candidiasis at baseline, 120 had Candida albicans and 2 had Candida tropicalis as the sole baseline pathogen whereas 44 had mixed baseline cultures containing C. albicans and one or more additional Candida species.

In the large, randomized, double-blind study comparing CANCIDAS 50 mg/day versus intravenous fluconazole 200 mg/day for the treatment of esophageal candidiasis, patients were treated for an average of 9 days (range 7-21 days). Favorable overall response at 5 to 7 days following discontinuation of study therapy, which required both complete resolution of symptoms and significant endoscopic improvement. The definition of endoscopic response was based on severity of disease at baseline using a 4-grade scale and required at least a two-grade reduction from baseline endoscopic score or reduction to grade 0 for patients with a baseline score of 2 or less.

The proportion of patients with a favorable overall response was comparable for CANCIDAS and fluconazole as shown in Table 13.

TABLE 13: Favorable Response Rates for Patients with Esophageal Candidiasis *   CANCIDAS Fluconazole % Difference†
(95% CI)
*
Analysis excluded patients without documented esophageal candidiasis or patients not receiving at least 1 day of study therapy.
†
Calculated as CANCIDAS – fluconazole 
Day 5-7 post-treatment 66/81 (81.5%) 80/94 (85.1%) -3.6 (-14.7, 7.5)

The proportion of patients with a favorable symptom response was also comparable (90.1% and 89.4% for CANCIDAS and fluconazole, respectively). In addition, the proportion of patients with a favorable endoscopic response was comparable (85.2% and 86.2% for CANCIDAS and fluconazole, respectively).

As shown in Table 14, the esophageal candidiasis relapse rates at the Day 14 post-treatment visit were similar for the two groups. At the Day 28 post-treatment visit, the group treated with CANCIDAS had a numerically higher incidence of relapse; however, the difference was not statistically significant.

TABLE 14: Relapse Rates at 14 and 28 Days Post-Therapy in Patients with Esophageal Candidiasis at Baseline   CANCIDAS Fluconazole % Difference*
(95% CI)
*
Calculated as CANCIDAS – fluconazole 
Day 14 post-treatment
Day 28 post-treatment 7/66 (10.6%)
18/64 (28.1%) 6/76 (7.9%)
12/72 (16.7%) 2.7 (-6.9, 12.3)
11.5 (-2.5, 25.4)

In this trial, which was designed to establish noninferiority of CANCIDAS to fluconazole for the treatment of esophageal candidiasis, 122 (70%) patients also had oropharyngeal candidiasis. A favorable