CLINICAL-TRIAL OF TACROLIMUS VERSUS CYCLOSPORINE IN LUNG TRANSPLANTATION

Background. A prospective clinical trial was undertaken to compare the efficacy of tacrolimus (FK 506) versus cyclosporine as the primary im munosuppressive agent after lung transplantation. Methods. Between Oct ober 1991 and May 1994, 133 single-lung and bilateral-lung recipients were randomized to receive either cyclosporine (n = 67) or tacrolimus (n = 66). The two groups were similar in age, sex, and underlying dise ase.Results. One-year and 2-year survival rates were similar in the tw o groups, although the trend was toward increased survival with tacrol imus. Acute rejection episodes per 100 patient-days were fewer (p = 0. 07) in the tacrolimus group (0.85) than in the cyclosporine group (1.0 9). Obliterative bronchiolitis developed in significantly fewer patien ts in the tacrolimus group (21.7%) compared with the cyclosporine grou p (38%) (p = 0.025), and there was greater freedom from obliterative b ronchiolitis over time for patients receiving tacrolimus (p < 0.03). S ignificantly more cyclosporine-treated patients (n = 13) required cros sover to tacrolimus than tacrolimus-treated patients to cyclosporine ( n = 2) (p = 0.02). The switch to tacrolimus controlled persistent acut e rejection in 6 of 9 patients. The overall incidence of infections wa s similar in the two groups, although bacterial infections were more c ommon with cyclosporine (p = 0.0375), whereas the risk of fungal infec tion was higher with tacrolimus (p < 0.05). Conclusions. This trial de monstrates the advantage of tacrolimus in reducing the risk of obliter ative bronchiolitis, the most important cause of long-term morbidity a nd mortality after lung transplantation.