Caspofungin is an echinocandin antifungal with a spectrum of activity that includes Candida albicans, non-albicans Candida spp., and Aspergillus spp. The echinocandins have a unique mechanism of action and inhibit the synthesis of 1,3-β-D-glucan in the fungal cell wall; there is no cross resistance expected with azoles and polyene antifungals. Caspofungin has a half-life of 9 to 11 hours, and because of its very low oral bioavailability can only be administered intravenously. The initial clinical evaluation of caspofungin was in 1996. There were several considerations in selecting the first study in patients. As an IV only agent, it was important that the fungal infection that was serious enough so that intravenous therapy was appropriate. However, there were no clinical data on treatment of any fungal infection with an echinocandin, so it was important that the infection that was not life threatening in case treatment was found to be ineffective. Another consideration was that the fungal infections potentially treatable by caspofungin were relatively uncommon, so it was also important that the disease selected had standardized criteria for diagnosis and response to treatment so that a multinational trial was feasible.
The initial clinical trial of caspofungin was conducted in patients with esophageal candidiasis. This was a double-blind, randomized, comparative, dose ranging study in which doses of caspofungin were compared to treatment with amphotericin B. The design and conduct of this initial trial will be reviewed and the key features of the subsequent development of caspofungin will be highlighted.
