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| |  Fixed Dose/Titration Strategy for Deferasirox Provides Clinically Acceptable Chelation in Patients With Iron Overload: Presented at ASH By Emma Hitt, PhD SAN FRANCISCO -- December 11, 2008 -- A fixed starting dose of deferasirox based on the patient's iron burden followed by ongoing dose titrations every 3 months appears to be an effective strategy for reducing iron burden in iron-overloaded patients, according to results from a study presented here at the American Society of Hematology (ASH) 50th Annual Meeting and Exposition. Investigator Maria Domenica Cappellini, MD, Department of Internal Medicine, University of Milan, Milan, Italy, discussed the findings from the Efficacy and Safety of Deferasirox (Exjade) in Patients With Transfusion-Dependent Anemias (EPIC) trial in a presentation on December 8. Deferasirox is an oral iron chelator taken once daily and is indicated for management of transfusional iron overload. In clinical trials, the starting dose of deferasirox was based on liver iron concentrations, which resulted in some patients not receiving adequate doses. The current study was designed to assess the efficacy and safety of fixed starting doses of deferasirox based on transfusion history, followed by subsequent dose titration based on serum ferritin levels. Dr. Cappellini reported on 1-year efficacy results in 1,744 patients with transfusion-dependent anaemia, including thalassaemia and myelodysplastic syndrome, sickle-cell disease, and aplastic anaemia and iron overload. The study evaluated an initial dose of 20 mg/kg/day for patients receiving 2 to 4 units of packed red blood cells per month. Patients receiving more frequent transfusions were considered for 30 mg/kg/day and those receiving less frequent transfusions were considered for 10 mg/kg/day. Dose adjustments were made in 5 to 10 mg/kg/day increments based on 3-month serum ferritin trends and safety markers. At 1 year of treatment with deferasirox, the 1,389 evaluable patients who completed the study had significantly reduced serum ferritin levels from baseline (median 264 ng/mL; P < .0001). Significant reductions in serum ferritin levels were noted in each of the dosing groups (average dose received of <20, 20 to <30, and >=30 mg/kg/day). In addition, patients in the >=30 mg/kg/day group experienced the greatest reductions. "The changes in serum ferritin from baseline observed in these dose categories were reflective of dosage adjustments and mean iron intake over the course of the study," the researchers noted. Reasons for discontinuing deferasirox included adverse events and abnormal laboratory values, lack of therapeutic effect, patient preference, protocol violation, and treatment no longer needed. Drug-related adverse events were mostly mild to moderate and included diarrhoea (14%), skin rash (10%), nausea (7.7%), and abdominal pain (5.6%). Serious adverse events deemed to be treatment-related were reported in 31 patients (59 events) and included rash, abdominal pain, and pyrexia. No progressive increases in serum creatinine levels were reported. Two consecutive alanine aminotransferase increases <5 times the limit of normal occurred in 6.9% of patients. "This large study supports the clinical approach of a fixed starting dose of deferasirox based on iron intake from ongoing blood transfusions and current iron burden, followed by prompt individual dose titration every 3 months according to serum ferritin trends and safety markers," the researchers concluded. The findings also confirmed that deferasirox is effective in reducing iron burden in iron-overloaded, regularly transfused patients with a wide range of underlying anaemias. Other results presented from the EPIC trial at the same session included the cardiac subgroup analysis, which showed that deferasirox was able to reduce cardiac iron in patients with beta-thalassaemia and to prevent cardiac iron overload in patients with beta-thalassaemia with normal cardiac iron levels at baseline. Funding for this research was provided by Novartis.
[Presentation title: Efficacy and Safety of Deferasirox (Exjade) in Patients With Transfusion-Dependent Anemias: 1-Year Results From the Large, Prospective, Multicenter EPIC Study. Abstract 3875]
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