BACKGROUND:Bortezomib (Velcade), a dipeptide boronate proteasome inhibitor, is a novel anti-cancer agent registered for multiple myeloma (MM). It has also shown promising clinical activity in non-small cell lung cancer (NSCLC). Clinical experience with bortezomib so far indicates that overall incidence of cardiac failure associated with bortezomib therapy remains incidental. Nevertheless, acute development or exacerbation of congestive cardiac failure has been associated with bortezomib treatment. CASE PRESENTATION:We present here a case of severe, but reversible, congestive cardiac failure in a lung cancer patient who had no prior cardiac history, after receiving an experimental treatment of bortezomib combined with chemotherapy. Elevated levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), as retrospectively measured in archived serum samples, were suggestive of pre-existent (sub-clinical) left ventricular dysfunction. CONCLUSION:Based on literature, we hypothesize that baseline presence of sub clinical cardiomyopathy, characterized by a dysregulation of the ubiquitin-proteasome system, could have predisposed this patient for a cardiac side effect induced by systemic proteasome inhibition. Patients with heart disease or risk factors for it should be closely monitored when being submitted to treatment with proteasome inhibition therapy such as bortezomib. Caution is therefore warranted in lung cancer patients who often present with cardiac comorbidities.

译文

背景:硼替佐米(Velcade)是一种二肽硼酸盐蛋白酶体抑制剂,是一种注册于多发性骨髓瘤(MM)的新型抗癌药。它还在非小细胞肺癌(NSCLC)中显示出令人鼓舞的临床活性。迄今为止,硼替佐米的临床经验表明,与硼替佐米治疗相关的心力衰竭总发生率仍然是偶然的。然而,硼替佐米治疗已引起充血性心力衰竭的急性发展或加重。
病例介绍:在此我们接受了硼替佐米的实验治疗和化学疗法治疗后,没有既往心脏史的肺癌患者发生严重但可逆的充血性心力衰竭的病例。回顾性分析在存档的血清样本中,N端前B型利尿钠肽(NT-proBNP)的水平升高提示左心功能不全(先前存在)。
结论:基于文献,我们假设以亚临床心肌病为基线存在,其特点是泛素-蛋白酶体系统功能失调,可能使该患者易受系统性蛋白酶体抑制所致的心脏副作用。当患有蛋白酶体抑制疗法(如硼替佐米)时,应密切监测患有心脏病或有此危险因素的患者。因此,对于经常表现出心脏合并症的肺癌患者,应格外小心。

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