A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with β-thalassemia
A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with β-thalassemia
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DOI：
10.1182/blood-2005-08-3430
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发表时间：
2006-05-01
期刊：
影响因子：
20.3
通讯作者：
Alberti, D
中科院分区：
文献类型：
--
作者：
Cappellini, MD;Cohen, A;Alberti, D
地拉罗司（ICL 670）是一种每日一次口服铁螯合剂，用于治疗输血引起的慢性铁过载。进行了一项比较性3期试验，以证明地拉罗司在2岁或2岁以上定期输血的β-地中海贫血患者中的疗效。患者随机接受地拉罗司（n = 296）或去铁胺（n = 290）治疗，根据基线肝脏铁浓度（LIC）给药。主要终点是LIC的维持或降低;次要终点包括安全性和耐受性、血清铁蛋白水平的变化和净体铁平衡。在两组中，LIC值为7 mg Fe/g干重（dw）或更高的患者的LIC和血清铁蛋白呈显著且相似的剂量依赖性降低，并对净身体铁平衡产生影响。然而，总体人群中未达到主要终点，可能是由于LIC值小于7 mg Fe/g dw的患者给予的地拉罗司剂量相对于去铁胺按比例降低。最常见的不良事件包括皮疹、胃肠道紊乱和血清肌酐轻度非进行性升高。粒细胞缺乏症、关节病或生长障碍与地拉罗司给药无关。地拉罗司是一种很有前途的每日一次口服疗法，用于治疗输血性铁超载。
Deferasirox (ICL670) is a once-daily oral iron chelator developed for the treatment of chronic iron overload from blood transfusions. A comparative phase 3 trial was conducted to demonstrate the efficacy of deferasirox in regularly transfused patients with beta-thalassemia aged 2 years or older. Patients were randomized and received treatment with deferasirox (n = 296) or deferoxamine (n = 290), with dosing of each according to baseline liver iron concentration (LIC). The primary endpoint was maintenance or reduction of LIC; secondary endpoints included safety and tolerability, change in serum ferritin level, and net body iron balance. In both arms, patients with LIC values of 7 mg Fe/g dry weight (dw) or higher had significant and similar dose-dependent reductions in LIC and serum ferritin, and effects on net body iron balance. However, the primary endpoint was not met in the overall population, possibly due to the fact that proportionally lower doses of deferasirox relative to deferoxamine were administered to patients with LIC values less than 7 mg Fe/g dw. The most common adverse events included rash, gastrointestinal disturbances, and mild nonprogressive increases in serum creatinine. No agranulocytosis, arthropathy, or growth failure was associated with deferasirox administration. Deferasirox is a promising once-daily oral therapy for the treatment of transfusional iron overload.