贝伐珠单抗致胃肠道穿孔的临床特点、机制与防治

The clinical characteristics, mechanism and prevention of gastrointestinal perforation due to bevacizumab

贝伐珠单抗为血管内皮细胞生长因子单克隆抗体，临床用于治疗结直肠癌、肺癌、乳腺癌、肾癌、恶性胶质瘤等。胃肠道穿孔（GIP）是贝伐珠单抗严重而少见的不良反应。GIP发生率因肿瘤种类不同而不一。GIP的临床症状与发生穿孔部位有关，主要为腹痛、恶心呕吐、发热等，也可出现盆腔疼痛，或因形成结肠．输尿管瘘而出现腹泻与泌尿系统感染症状。贝伐珠单抗致GIP的危险因素包括患者年龄、用药剂量、既往史、原发肿瘤类型和合并用药。贝伐珠单抗致GIP的机制包括抑制凝血因子、抑制肠壁细胞增殖和愈合、诱导肿瘤细胞死亡、降低肠壁稳定性等。对贝伐珠单抗致GIP的患者可采取手术或非手术（给予抗生素、全胃肠外营养）治疗。发生GIP的患者不能再使用贝伐珠单抗。

Bevacizumab, a monoclonal antibody to vascular endothelial growth factor,has been used in the treatment of eolorectal cancer, lung cancer, breast cancer, kidney cancer, and glioblastoma, etc. Gastrointestinal perforation （GIP） is a serious and unusual adverse reaction induced by bevacizumab. The incidence of GIP is different due to different types of tumor. The clinical manifestations of GIP are related to perforation site. The main symptoms include abdominal pain, nausea, vomiting, fever, pelvic pain, diarrhea and symptoms of urinary tract infection due to colon - ureter fistula. The risk factors of GIP induced by bevaeizumab include age, dosage, history of past illness, primary tumor type and combination of medications. The mechanisms of GIP induced by bevacizumab are inhibition of clotting factors, inhibition of intestinal wall cells＇ proliferation and healing, inducing tumor cell death, and reducing intestinal stability. The treatment of GIP induced by bevaeizumab are surgical or non-surgical therapy, the latter include antibiotics and total parenteral nutrition. The patient with GIP cannot receive bevacizumab again.