Randomized, double-blind, multicenter study of caspofungin versus amphotericin B for treatment of oropharyngeal and esophageal candidiases

Abstract

Caspofungin is an antifungal agent of the novel echinocandin class. We investigated its efficacy, safety, and tolerability as therapy for oropharyngeal and/or esophageal candidiasis in a phase II dose-ranging study. Patients were randomized in a double-blind manner to receive either caspofungin acetate (35, 50, or 70 mg) or amphotericin B (0.5 mg/kg of body weight) intravenously once daily for 7 to 14 days. A favorable response required both complete resolution of symptoms and quantifiable improvement of mucosal lesions 3 to 4 days after discontinuation of study drug. Efficacy was assessed using a modified intent-to-treat analysis. No hypothesis testing of efficacy was planned or performed. Of 140 enrolled patients, 63% had esophageal involvement and 98% were infected with the human immunodeficiency virus (HIV) (median CD4 count, 30/mm(3)). A modestly higher proportion of patients in each of the caspofungin groups (74 to 91%) achieved favorable responses compared to amphotericin B recipients (63%), but there was considerable overlap in the 95% confidence intervals surrounding these point estimates. Similar trends were found in the subgroups with esophageal involvement, a history of fluconazole failure, and CD4 counts of < or =50/mm(3). A smaller proportion of patients receiving any dose of caspofungin experienced drug-related adverse events compared to patients given standard doses of conventional amphotericin B (P < 0.01). Caspofungin provided a generally well-tolerated parenteral therapeutic option for HIV-infected patients with oropharyngeal and/or esophageal candidiasis in this study.

FIG. 1.

Combined favorable response rates in the caspofungin and amphotericin groups. Patients presenting with either esophageal or oropharyngeal candidiasis were treated with caspofungin (35, 50, and 70 mg) or amphotericin (0.5 mg/kg) daily for 7 to 14 days. Patients were evaluated 3 to 4 days after discontinuation of therapy. Numbers within the columns represent the total number of patients in each group included in the MITT analysis. Error bars represent the 95% confidence intervals.

FIG. 2.

Combined favorable response rates to caspofungin and amphotericin therapy by baseline CD4 lymphocyte count. CD4 cell counts were measured at screening. Numbers within the columns represent the total number of patients in each group. Error bars represent the 95% confidence intervals. The confidence interval was not calculated for the caspofungin 70-mg dose group having >50 CD4 cells/mm³ because the sample size was only seven patients.

FIG. 3.

Resolution of esophageal plaques caused by infection with C. albicans in two patients treated with caspofungin. Favorable endoscopic responses are illustrated for two representative patients with high-grade esophagitis 3 to 4 days after the conclusion of caspofungin therapy.