Discovery and development of first in class antifungal caspofungin (CANCIDAS®)--a case study.

Covering: 1985 to 2001.This paper describes a fifteen year journey from concept to clinical discovery and development of the first in class caspofungin acetate (CANCIDAS®) a parenteral antifungal agent. Caspofungin is a semisynthetic derivative of pneumocandin B0, a naturally occurring, lipophilic cyclic peptide isolated from the fungus, Glarea lozoyensis.

Advances in antifungal therapy.

The prevalence of invasive fungal infections (IFIs) has increased over the past three decades owing to the increasing numbers of immunocompromised hosts. These infections are associated with significant morbidity and mortality. Recent significant advances in antifungal therapy include the broad-spectrum triazoles (voriconazole and posaconazole) and a new class of antifungals, the echinocandins (caspofungin, micafungin, and anidulafungin).

Invasive candidiasis treated in the intensive care unit: observations from a randomized clinical trial.

Objectives: The objectives of this study were to contrast risk factors, microbiology, and outcomes in patients with invasive candidiasis treated in an intensive care unit (ICU) with those in patients with invasive candidiasis treated outside an ICU and to describe therapeutic results with caspofungin in ICU patients.

Materials And Methods: We retrospectively identified patients with documented invasive candidiasis who received their first dose of the study drug in the ICU as part of a double-blind randomized trial. Participants were not stratified at entry by their ICU status.

Pharmacokinetics, safety, and tolerability of caspofungin in children and adolescents.

Caspofungin is a parenteral antifungal that inhibits beta-1,3-D-glucan synthesis. Although licensed for adult use, the appropriate caspofungin dosing regimen in pediatric patients is not yet known. We therefore investigated the pharmacokinetics and safety of caspofungin in pediatric patients.

Invasive candidiasis in cancer patients: observations from a randomized clinical trial.

Background: Invasive candidiasis is a common and serious complication of cancer and its therapy.

Methods: We retrospectively identified patients with malignancies enrolled in a double-blind randomized trial of caspofungin (50 mg/day after a 70 mg loading dose) vs. conventional amphotericin B (0.

Salvage therapy with caspofungin for invasive aspergillosis: results from the caspofungin compassionate use study.

Objectives: The objective was to prospectively assess the efficacy and safety of caspofungin as salvage therapy for invasive aspergillosis in patients enrolled in the caspofungin compassionate-use study.

Methods: Forty-eight patients with invasive Aspergillus infections (36 with pulmonary infection, 12 with extrapulmonary or disseminated infection) were enrolled in this study. All patients were refractory to or intolerant of intravenous amphotericin B or a lipid amphotericin formulation(s).

Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy.

Background: Invasive aspergillosis (IA) is an important cause of morbidity and mortality among immunocompromised patients. Echinocandins are novel antifungal molecules with in vitro and in vivo activity against Aspergillus species.

Methods: We investigated the efficacy and safety of caspofungin in the treatment of IA.

Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia.

Background: Patients with persistent fever and neutropenia often receive empirical therapy with conventional or liposomal amphotericin B for the prevention and early treatment of invasive fungal infections. Caspofungin, a member of the new echinocandin class of compounds, may be an effective alternative that is better tolerated than amphotericin B.

Methods: In this randomized, double-blind, multinational trial, we assessed the efficacy and safety of caspofungin as compared with liposomal amphotericin B as empirical antifungal therapy.

Second-line therapy with caspofungin for mucosal or invasive candidiasis: results from the caspofungin compassionate-use study.

Objectives: To prospectively assess the efficacy and safety of caspofungin as second-line therapy for mucosal or invasive candidiasis in patients enrolled in the caspofungin compassionate-use study.

Materials And Methods: Thirty-seven patients with mucosal or invasive candida infections (17 oesophageal, four oropharyngeal and 16 invasive candidiasis) were enrolled in the caspofungin compassionate-use study. All patients were refractory to or intolerant of intravenous amphotericin B or lipid amphotericin formulation(s).

Efficacy of caspofungin in the treatment of esophageal candidiasis resistant to fluconazole.

Caspofungin is a new echinocandin drug with comparable in vitro activity against azole-susceptible and -resistant isolates of that could provide a less toxic alternative to amphotericin B for the management of esophageal candidiasis with clinical or laboratory evidence of decreased susceptibility to fluconazole. The authors retrospectively analyzed its efficacy in adults with endoscopically documented esophagitis from four Phase II and III studies using two definitions of resistance to fluconazole: 1) clinically refractory infection based on failure of esophageal symptoms to improve despite at least 1 week of >or=200 mg/d of fluconazole; or 2) microbiologically resistant infection with either "susceptible dose-dependent" or "resistant" isolates based on MICs of 16 to 32 and >or=64 microg fluconazole/mL, respectively. A favorable response required resolution of all symptoms and substantial improvement in endoscopic findings.

A randomized double-blind study of caspofungin versus fluconazole for the treatment of esophageal candidiasis.

Background: Candida esophagitis remains an important cause of morbidity in patients with advanced human immunodeficiency virus (HIV) infection. Fluconazole is widely regarded as the treatment of choice for this condition.

Methods: The efficacy and safety of caspofungin were compared with fluconazole in adult patients with Candida esophagitis in a double-blind randomized trial.

Response and relapse rates of candidal esophagitis in HIV-infected patients treated with caspofungin.

Caspofungin is a new antifungal drug of the echinocandin class. We analyzed the clinical efficacy of caspofungin (50 mg/day) in the treatment of HIV-infected adults with endoscopically documented Candida esophagitis and enrolled in four clinical trials of caspofungin. Symptoms were evaluated daily; a favorable outcome required complete resolution of all esophageal symptoms assessed at the time of discontinuation of therapy.

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

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.