盐酸阿那格雷胶囊治疗原发性血小板增多症的有效性和安全性——多中心、随机对照临床研究

Efficacy and safety of anagrelide in treatment of essential thrombocythemia： multicenter, randomized controlled clinical trial

目的 评价阿那格雷治疗原发性血小板增多症（ET）的有效性和安全性.方法 将符合WHO 2008诊断标准的ET患者随机分配到阿那格雷组和羟基脲组.阿那格雷由2mg/d始逐渐增加,最大剂量为10 mg/d,维持PLT（100～400）×109/L1个月后,逐渐减量维持.羟基脲由1 000 mg/d逐渐增加,维持PLT（100～400）×109/L1个月后,减量至10mg·kg-1·d-1维持.共观察12周.结果 17个中心共人组222例ET患者（阿那格雷组、羟基脲组分别为113、109例）,198例可评价疗效（阿那格雷组、羟基脲组分别为97、101例）.治疗12周,阿那格雷组血液学缓解率为87.63％（85/97）,羟基脲组为88.12％（89/101）,差异无统计学意义（P=0.174）.阿那格雷组治疗前中位PLT为827（562～1 657）×109/L,治疗12周为400（127～1 130）×109/L,差异有统计学意义（P＜0.001）.阿那格雷组治疗后PLT降低值中位数为393（-362～1 339）×109/L,羟基脲组为398（-579～1 846）×109/L,差异无统计学意义（P=0.982）.阿那格雷组、羟基脲组中位起效时间分别为7（3～14）、21（14～28）d,差异有统计学意义（P=0.003）.阿那格雷组不良事件发生率为65.49％（74/113）,包括心悸（36.28％）、头痛（21.24％）、乏力（14.16％）和头晕（11.50％）等,均为Ⅰ～Ⅱ级.结论 盐酸阿那格雷胶囊治疗ET的血液学缓解率与羟基脲相近,不良事件发生率相似,起效时间较短,无明显血液学毒性,安全性较好.

Objective To evaluate the efficacy and safety of anagrelide in essential thrombocythemia （ET）.Methods Patients who diagnosed as ET according to the World Health Organization classification were enrolled.Each patient was assigned to take anagrelide hydrochloride capsule or hydroxyurea tablet by random 1 ∶ 1 ratio.Dose of anagrelide started at 2 mg/d,then increased gradually and the maximum dose was 10 mg/d until the platelet counts dropped to （100-400）× 109/L,one month later gradually reduced to maintain dose.The dose of hydroxyurea was 1000 mg/d at beginning,then increased gradually,when platelet counts dropped to （100-400） × 109/L and kept for one month,reduced to maintain dose as 10 mg· kg-1· d-1.The observation period was 12 weeks.Results A total of 222 patients were enrolled in seventeen centers （including 113 patients treated with anagrelide and 109 with hydroxyurea）.Therapy efficacy can be evaluated in 198 patients （including 97 patients administered with anagrelide and 101 with hydroxyurea）.At 12～ weeks of therapy,the hematologic remission rate was 87.63% （85/97） in anagrelide group and 88.12% （89/107） in hydroxyurea group,the differences between the two groups were not significant （P=0.173）.Treatment with anagrelide lowered the platelet counts by a median of 393 （362-1 339） × 109/L from a median of 827 （562-1657） × 109/L at the beginning of the observation to 400 （127-1130） × 109/L after 12 weeks （P〈0.001）,which were similar to the treatment result of hydroxyurea by a median drop of 398 （597-1846）× 109/L （P=0.982）.The median time to achieving response of anagrelide group was 7 （3-14） days,superior to that of hydroxyurea for 21 （14-28） significantly （P=0.003）.Frequency of anagrelide related adverse events was 65.49 % （74/113）,including cardiopalmus （36.28%）,headache （21.24%）,fatigue （14.16%） and dizzy （11.50%）.Conclusion Anagrelide was effective in patients with ET which had similar hematologic remission rate to hydroxyurea and could take effect more quickly than hydroxyurea.Incidence of adverse events was undifferentiated between anagrelide and hydroxyurea,but anagrelide treatment had tolerable adverse effects and no hematologic toxicity.