Departments of Infectious Diseases and Oncology, University Hospital Vall d'Hebron, Autonomous University of Barcelona, Barcelona, Spain.
Unit of Infectious Diseases, Hospital Universitario '12 de Octubre', Instituto de Investigación Hospital '12 de Octubre' (i + 12), School of Medicine, Universidad Complutense, Madrid, Spain; Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain.
Clin Microbiol Infect. 2018 Jun;24 Suppl 2:S41-S52. doi: 10.1016/j.cmi.2017.12.027. Epub 2018 Feb 7.
The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) consensus document on the safety of targeted and biologic therapies.
To review, from an infectious diseases perspective, the safety profile of therapies targeting cell surface receptors and associated signaling pathways among cancer patients and to suggest preventive recommendations.
Computer-based Medline searches with MeSH terms pertaining to each agent or therapeutic family.
Vascular endothelial growth factor (VEGF)-targeted agents (bevacizumab and aflibercept) are associated with a meaningful increase in the risk of infection, likely due to drug-induced neutropaenia, although no clear benefit is expected from the universal use of anti-infective prophylaxis. VEGF tyrosine kinase inhibitors (i.e. sorafenib or sunitinib) do not seem to significantly affect host's susceptibility to infection, and universal anti-infective prophylaxis is not recommended either. Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab or panitumumab) induce neutropaenia and secondary skin and soft tissue infection in cases of severe papulopustular rash. Systemic antibiotics (doxycycline or minocycline) should be administered to prevent the latter complication, whereas no recommendation can be established on the benefit from antiviral, antifungal or anti-Pneumocystis prophylaxis. A lower risk of infection is reported for anti-ErbB2/HER2 monoclonal antibodies (trastuzumab and pertuzumab) and ErbB receptor tyrosine kinase inhibitors (including dual-EGFR/ErbB2 inhibitors such as lapatinib or neratinib) compared to conventional chemotherapy, presumably as a result of the decreased occurrence of drug-induced neutropaenia.
With the exception of VEGF-targeted agents, the overall risk of infection associated with the reviewed therapies seems to be low.
本综述是欧洲临床微生物学和传染病学会（ESCMID）感染宿主研究组（ESGICH）关于靶向和生物治疗安全性的共识文件的一部分。
从传染病学的角度回顾针对癌症患者细胞表面受体及其相关信号通路的治疗方法的安全性概况，并提出预防建议。
针对每种药物或治疗药物家族的 MeSH 术语进行计算机检索。
血管内皮生长因子（VEGF）靶向药物（贝伐珠单抗和阿柏西普）与感染风险显著增加相关，这可能是由于药物引起的中性粒细胞减少，但普遍使用抗感染预防措施并不能带来明显的益处。VEGF 酪氨酸激酶抑制剂（即索拉非尼或舒尼替尼）似乎不会显著影响宿主对感染的易感性，也不建议普遍使用抗感染预防措施。抗表皮生长因子受体（EGFR）单克隆抗体（西妥昔单抗或帕尼单抗）在严重脓疱性皮疹的情况下会引起中性粒细胞减少和继发性皮肤和软组织感染。应给予全身抗生素（多西环素或米诺环素）预防后者的并发症，而抗病毒、抗真菌或抗肺孢子菌预防的益处尚无法确定。与传统化疗相比，抗 ErbB2/HER2 单克隆抗体（曲妥珠单抗和帕妥珠单抗）和 ErbB 受体酪氨酸激酶抑制剂（包括双重 EGFR/ErbB2 抑制剂，如拉帕替尼或奈拉替尼）的感染风险较低，这可能是由于药物引起的中性粒细胞减少发生率降低所致。
除了 VEGF 靶向药物外，所审查的治疗方法相关的总体感染风险似乎较低。
