Deferasirox: an update.

Cumulative data from prospective studies in over 3,000 patients with a range of transfusion dependent anemias have established key principles about the efficacy and safety of deferasirox (DFS). Pivotal preregistration studies established the relationship between dose, iron excretion, and tolerability using changes in liver iron concentration (LIC) to measure changes in body iron. The importance of the transfusional iron-loading rate to treatment response has been clearly demonstrated. Unwanted effects in these core studies included skin rash and gastrointestinal disturbances. Serum creatinine increments were initially seen in about one-third of patients but have not been progressive in study extensions up to 4.5 years. The proportion of patients with serum ferritin <1,000 microg/L has risen steadily without an increase in adverse events and doses >30 mg/kg/day have been given in >200 patients without an increase in adverse events. The large-scale EPIC trial involving >1,600 patients has revealed further insights about the interaction of dose with ferritin trends and safety markers. Cardiac substudies of this trial, in >100 patients with established mild to moderate myocardial iron loading by T2*, show a significant reduction in cardiac iron.