Eltrombopag for the treatment of thrombocytopenia in patients with malignant and non-malignant hematologic disorders

埃尔特罗姆博帕格 医学 髓系白血病 骨髓增生异常综合症 内科学 肿瘤科 血小板生成素受体 临床试验 白血病 血小板 血小板生成素 免疫学 免疫性血小板减少症 造血 骨髓 干细胞 生物 遗传学
作者
Swati Pathak,Michael Roth,Amit Verma,Ulrich Steidl
出处
期刊:Expert Opinion on Drug Metabolism & Toxicology [Informa]
卷期号:9 (12): 1667-1675 被引量:10
标识
DOI:10.1517/17425255.2013.858119
摘要

Introduction: Eltrombopag (EP) is an orally bioavailable, non-peptide, thrombopoietin receptor (TPO-R) agonist developed to stimulate platelet production. EP is a small hydrazone molecule which interacts with the transmembrane domain of TPO-R and promotes megakaryopoiesis, and a subsequent increase in platelet number. To date, multiple large clinical trials have demonstrated the ability of EP to reduce the burden of thrombocytopenia and its associated side effects in patients with chronic immune thrombocytopenia purpura and patients with hepatitis-C related thrombocytopenia. Given these promising results and the morbidity associated with thrombocytopenia in cancer patients, there is significant interest in investigating the role of EP for thrombocytopenia secondary to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Areas covered: In this review, the authors address the potential utility of EP for patients with AML and MDS with thrombocytopenia. The review provides an overview of the rationale for the development of EP in AML and MDS, and the mechanism(s) of action of EP. The authors focus on preclinical data describing the effectiveness of EP as both a platelet-stimulating, and an anti-leukemia agent and describe the use of EP in clinical trials. Expert opinion: EP has the potential to be an effective supportive care agent, improving platelet counts and decreasing thrombocytopenia-related morbidity, in patients with AML and MDS. Large, randomized clinical trials are needed to assess the efficacy of EP in reducing the duration and severity of thrombocytopenia, as well assess the clinical utility of EP as an anti-leukemia agent.

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