Center for Global Health, Baylor College of Medicine and Texas Children's Hospital, 1102 Bates Street, Houston, TX 77030, USA.
C R Biol. 2013 Mar;336(3):177-82. doi: 10.1016/j.crvi.2012.09.006. Epub 2012 Nov 9.
Due to its oral route of administration and mild toxicity profile, as well as its potent laboratory and clinical effects, hydroxyurea (or hydroxycarbamide) has been the primary focus of fetal hemoglobin (HbF) induction strategies for the treatment of children with sickle cell anemia (SCA). When administered orally once a day, hydroxyurea treatment is very well tolerated with little short-term toxicity. Hydroxyurea has documented laboratory efficacy with increases in Hb and HbF; treatment also significantly reduces the number of painful episodes, acute chest syndrome, transfusions, and hospitalizations. Most young patients reach a maximum tolerated dose of hydroxyurea at 25-30 mg/kg/d, where they will achieve key laboratory thresholds (Hb ≥ 9 g/dL and HbF ≥ 20%) without excessive myelosuppression. Potential long-term toxicities continue to be of great concern and should be monitored in all patients with SCA who receive hydroxyurea therapy. To date, however, no increases in stroke, myelodysplasia, or carcinogenicity have been detected in SCA patient cohorts, with drug exposure now reaching 15 years for some treated children. Taken together, available evidence suggests that hydroxyurea represents an inexpensive and effective treatment option that should be offered to most, if not all, patients with SCA. As countries in Africa develop newborn screening programs to identify SCA, the widespread use of hydroxyurea may prove to be a useful treatment to help ameliorate the disease in resource-limited settings. Hydroxyurea is the only currently available disease-modifying therapy for SCA, and is emerging as a safe and effective treatment for all patients with SCA, in both developed and developing countries.
由于羟脲（或羟基脲）具有口服途径和轻微的毒性特征，以及其在实验室和临床方面的强大效果，因此它一直是治疗镰状细胞贫血（SCA）儿童的胎儿血红蛋白（HbF）诱导策略的主要重点。当每天口服一次时，羟脲治疗的耐受性非常好，短期毒性很小。羟脲具有增加 Hb 和 HbF 的实验室功效；治疗还显著减少了疼痛发作、急性胸部综合征、输血和住院的次数。大多数年轻患者在 25-30 mg/kg/d 的剂量下达到最大耐受剂量，在此剂量下，他们将达到关键的实验室阈值（Hb≥9 g/dL 和 HbF≥20%），而不会出现过度的骨髓抑制。潜在的长期毒性仍然是一个非常令人关注的问题，应在所有接受羟脲治疗的 SCA 患者中进行监测。然而，迄今为止，在 SCA 患者队列中没有发现中风、骨髓增生异常或致癌性增加的情况，一些接受治疗的儿童的药物暴露现在已经达到 15 年。总的来说，现有证据表明，羟脲是一种廉价有效的治疗选择，应提供给大多数（如果不是全部）SCA 患者。随着非洲国家开发新生儿筛查计划以识别 SCA，羟脲的广泛使用可能被证明是一种在资源有限的环境中帮助改善疾病的有用治疗方法。羟脲是目前唯一可用的 SCA 疾病修饰治疗药物，正在成为发达国家和发展中国家所有 SCA 患者的安全有效治疗方法。
