Arora Nivedita, Gupta Arjun, Singh Preet Paul
Department of Internal Medicine, University of Texas Southwestern Medical Centre, Dallas, TX, USA.
Division of Hematology/Oncology, Springfield Clinic Cancer Center, Springfield, Illinois, USA.
J Gastrointest Oncol. 2017 Jun;8(3):485-498. doi: 10.21037/jgo.2017.01.07.
Biological therapy comprises agents that by virtue of their unique mechanisms of action, are able to specifically incite a response against or target malignant cells. They differ from conventional chemotherapy with regard to mechanisms of action, indications and side effect profile. Biologic agents have revolutionized therapy for a number of malignancies. In the setting of gastrointestinal (GI) malignancies, agents targeting vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (Her2/Neu) and epidermal growth factor receptor (EGFR) have proven to be invaluable additions to chemotherapy. However, these agents bring with them a set of side effects attributable to their unique mechanisms of action. The anti VEGF agents-bevacizumab, aflibercept and ramucirumab, can result in renal and vascular complications such as hypertension, arterial thrombotic events (ATE), proteinuria and GI perforations. The anti EGFR agents classically cause dermatological toxicities, in addition to hypomagnesemia, which can be dose limiting for patients. Trastuzumab, a monoclonal antibody that targets Her2/Neu, is known to cause cardiotoxicity, especially when used with anthracyclines. Use of immunotherapy agents such as nivolumab is associated with the development immune related adverse events (irAEs). The use of these agents is expected to increase over the next few years and it is crucial that patients and practitioners are aware of their adverse effects and current management strategies. This review highlights the adverse events associated with the use of biologic and immunologic therapies in GI cancers, their incidence and current management strategies.
生物疗法包含一些药物,这些药物凭借其独特的作用机制,能够特异性地激发针对恶性细胞的反应或靶向恶性细胞。它们在作用机制、适应证和副作用方面与传统化疗有所不同。生物制剂已经彻底改变了多种恶性肿瘤的治疗方法。在胃肠道恶性肿瘤的治疗中,靶向血管内皮生长因子(VEGF)、人表皮生长因子受体2(Her2/Neu)和表皮生长因子受体(EGFR)的药物已被证明是化疗中非常有价值的补充。然而,这些药物也带来了一系列归因于其独特作用机制的副作用。抗VEGF药物——贝伐单抗、阿柏西普和雷莫西尤单抗,可导致肾脏和血管并发症,如高血压、动脉血栓形成事件(ATE)、蛋白尿和胃肠道穿孔。抗EGFR药物除了可导致低镁血症外,还常引起皮肤毒性,而低镁血症对患者来说可能是剂量限制性的。曲妥珠单抗是一种靶向Her2/Neu的单克隆抗体,已知会引起心脏毒性,尤其是与蒽环类药物联合使用时。使用免疫治疗药物如纳武单抗与发生免疫相关不良事件(irAE)有关。预计在未来几年这些药物的使用将会增加,患者和从业者了解其不良反应及当前的管理策略至关重要。本综述重点介绍了胃肠道癌症中使用生物疗法和免疫疗法相关的不良事件、其发生率及当前的管理策略。