奥希替尼超剂量致血小板减少症1例并文献分析

Thrombocytopenia Induced by Overdose of Osimertinib:A Case Report and Literature Analysis

目的为临床安全使用奥希替尼提供参考。方法回顾性分析山东第一医科大学附属省立医院收治的1例左肺腺癌伴表皮生长因子受体(EGFR)p.L858R基因突变患者超剂量使用奥希替尼致血小板减少的治疗过程。检索PubMed、中国知网、万方、维普等数据库(自建库起至2023年4月25日)相关文献探讨其发生机制及临床治疗对策。结果患者服用奥希替尼80 mg/d 2年余,发生脑膜转移后加量至160 mg/d,24 d后发生血小板减少症(3级)。考虑“很可能”为奥希替尼超量所致(诺氏不良反应评估量表评分为7分),遂停用奥希替尼,16 d后血小板计数恢复正常。分析文献可知,奥希替尼致血小板减少症可能的机制包括干扰血小板生成或激活过程,受到抑制的肿瘤细胞与血小板之间可能存在致病反馈通路,以及影响内源性血小板生成素水平。该药品不良反应发生时,需暂停或减量相关药物,推荐给予重组人白细胞介素11或重组人血小板生成素等治疗。结论对于脑膜转移患者,高剂量奥希替尼能有效提高血脑屏障通透率,最大限度地抑制肿瘤生长,但超剂量使用过程中,临床医务人员需更加关注血小板减少症的发生,增强安全用药意识,结合患者病情及时对症处理。

Objective To provide a reference for the safe use of osimertinib in clinical practice.Methods The treatment process of a patient with left lung adenocarcinoma and epidermal growth factor receptor(EGFR)p.L858R gene mutation experiencing thrombocytopenia induced by overdose of osimertinib in the Shandong Provincial Hospital Affiliated to Shandong First Medical University was retrospectively analyzed.The relevant literature in the PubMed,CNKI,WanFang,VIP and others from the inception of these databases to April 25,2023 was searched to explore the mechanism of this adverse drug reaction(ADR)and clinical countermeasures.Results After taking 80 mg/d of osimertinib for more than two years,the patient developed meningeal metastasis,and thrombocytopenia(grade three)occurred when she took at a more dosage of 160 mg/d for 24 d.The ADR was considered to be probably related to the overdose of osimertinib(the Naranjo′s ADR evaluation scale was seven points),so the osimertinib was discontinued,and then the patient′s platelet count returned to the normal after 16 d.Literature analysis showed that the possible mechanisms of thrombocytopenia induced by osimertinib included interference with platelet generation or activation,possible pathogenic feedback pathways between suppressed tumor cells and platelets,and effects on endogenous thrombopoietin level.When this ADR occurred,we should stop the relevant drugs or reduce the dosage,and give the treatment such as recombinant human interleukin-11 or recombinant human thrombopoietin.Conclusion For patients with meningeal metastasis,high-dose osimertinib can effectively improve blood-brain barrier permeability and inhibit tumor growth.However,during the overdose use of osimertinib,clinical medical personnel need to pay more attention to the occurrence of thrombocytopenia,enhance the awareness of safe medication,and give the timely and symptomatic treatment based on the patient′s condition.