A Phase 1/2, Dose-Escalation Trial of Deferasirox for the Treatment of Iron Overload in HFE-Related Hereditary Hemochromatosis

摘要: Hereditary hemochromatosis (HH) is characterized by increased intestinal iron absorption that may result in overload. Although phlebotomy widely practiced, it poorly tolerated or contraindicated patients with anemias, severe heart disease, poor venous access, and compliance can vary. The once-daily, oral chelator, deferasirox (Exjade) provide an alternative treatment option. Patients HH carrying the HFE gene who were homozygous for Cys282Tyr mutation, serum ferritin levels of 300-2000 ng/mL, transferrin saturation ≥45%, no known history cirrhosis enrolled this dose-escalation study to characterize safety efficacy deferasirox, comprising a core extension phase (each 24 weeks). Forty-nine received starting doses 5 (n = 11), 10 15), 15 23) mg/kg/day. Adverse events generally dose-dependent, most common being diarrhea, headache, nausea 18, n 10, 8 1, 0 extension, respectively). More mg/kg/day than cohorts experienced increases alanine aminotransferase creatinine during 48-week period; six had >3× baseline greater upper limit normal range, eight >33% above on two consecutive occasions. After receiving 48 weeks, median decreased 63.5%, 74.8%, 74.1% 5, cohorts, respectively. In all <250 ng/mL. Conclusion: Deferasirox reduce burden HH. Based results, at appears be appropriate further patient population. (Hepatology 2010)