Chaudhary Preeti, Gajra Ajeet
Department of Medicine, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
Cardiovasc Hematol Agents Med Chem. 2010 Jul;8(3):156-63. doi: 10.2174/187152510791698370.
Molecular inhibition of the epidermal growth factor receptor (EGFR) is a promising anticancer strategy and monoclonal antibodies (mAbs) to EGFR are undergoing extensive evaluation in preclinical and clinical trials. EGFR is frequently over expressed in many types of human malignancy and may be associated with prognosis, disease stage and survival. Therefore, EGFR represents an attractive target for cancer therapy. Two such agents that inhibit EGFR signaling by interfering with ligand-binding are cetuximab (Erbitux) and panitumumab (Vectibix). Common toxicities of agents targeting the EGFR differ from those associated with traditional chemotherapy. Although rare, cardiac toxicity is a significant complication associated with cetuximab and the clinical spectrum of these toxicities can range from subclinical abnormalities to being catastrophic, life-threatening and sometimes fatal events. This review aims to highlight an important albeit inadequately studied toxicity related to EGFR mAbs. We shall review preclinical and clinical literature to ascertain the etiology, incidence and management of cardiovascular complications of monoclonal antibodies to EGFR. As the potential clinical applications for these agents increase, clinicians using these agents need to remain vigilant regarding cardiovascular complications, especially in view of an aging cancer population.
对表皮生长因子受体(EGFR)进行分子抑制是一种很有前景的抗癌策略,针对EGFR的单克隆抗体(mAb)正在临床前和临床试验中接受广泛评估。EGFR在多种人类恶性肿瘤中经常过度表达,可能与预后、疾病分期和生存期有关。因此,EGFR是癌症治疗中一个有吸引力的靶点。西妥昔单抗(爱必妥)和帕尼单抗(维克替比)是两种通过干扰配体结合来抑制EGFR信号传导的药物。靶向EGFR药物的常见毒性与传统化疗相关毒性不同。心脏毒性虽然罕见,但却是与西妥昔单抗相关的一种严重并发症,这些毒性的临床谱范围可从亚临床异常到灾难性、危及生命甚至有时是致命事件。本综述旨在强调一种与EGFR单克隆抗体相关的重要但研究不足的毒性。我们将回顾临床前和临床文献,以确定针对EGFR单克隆抗体的心血管并发症的病因、发生率和处理方法。随着这些药物潜在临床应用的增加,使用这些药物的临床医生需要对心血管并发症保持警惕,尤其是考虑到癌症患者群体老龄化的情况。