Division of Hematology Oncology, Massachusetts General Hospital, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Expert Rev Hematol. 2021 May;14(5):437-448. doi: 10.1080/17474086.2021.1924053. Epub 2021 May 13.
: Chemotherapy-induced thrombocytop enia (CIT) is a common complication of cancer treatment causing chemotherapy delays, dose reductions, and treatment discontinuation, negatively impacting treatment outcomes and putting patients at risk for bleeding complications. There is no FDA-approved agent available to manage CIT.: This article covers the diagnosis, definitions, and clinical challenges of CIT, and then focuses on the therapeutics developed to manage CIT. The first-generation thrombopoietic agents (oprelvekin and recombinant human thrombopoietins) are reviewed for critical background and context, followed by a detailed discussion of the data for the thrombopoietin receptor agonists (TPO-RAs) to manage CIT. Efficacy of TPO-RAs in treatment and prevention of CIT, as well as safety concerns such as the risk of thromboembolic complications, are reviewed in detail. For this review, a PubMed/MEDLINE literature search was undertaken for relevant articles published from 1995-2021.: After over two decades of drug development for CIT, multiple clinical trials and observational studies have found TPO-RAs, in particular romiplostim, to be safe and effective agents to manage patients with CIT, although no agent is yet FDA-approved for this indication. Active management of CIT with TPO-RAs is likely to improve oncologic outcomes, although additional data are needed. Phase 3 trials are ongoing.
化疗引起的血小板减少症(CIT)是癌症治疗的常见并发症,导致化疗延迟、剂量减少和治疗中断,对治疗结果产生负面影响,并使患者面临出血并发症的风险。目前尚无获得 FDA 批准的药物可用于治疗 CIT。
本文涵盖了 CIT 的诊断、定义和临床挑战,然后重点介绍了为管理 CIT 而开发的治疗方法。首先回顾了第一代促血小板生成素(oprelvekin 和重组人血小板生成素)的关键背景和情况,然后详细讨论了用于管理 CIT 的血小板生成素受体激动剂(TPO-RA)的数据。详细审查了 TPO-RA 在治疗和预防 CIT 中的疗效以及安全性问题,例如血栓栓塞并发症的风险。为了进行本次综述,对 1995 年至 2021 年期间发表的相关文章进行了 PubMed/MEDLINE 文献检索。
经过二十多年的 CIT 药物开发,多项临床试验和观察性研究发现,TPO-RA,特别是 romiplostim,是安全有效的治疗 CIT 患者的药物,尽管尚无药物获得 FDA 批准用于该适应症。积极使用 TPO-RA 治疗 CIT 可能会改善肿瘤学结果,但需要更多的数据。正在进行 3 期试验。