Fan Yuanchun, Liu Shihao, Zhao Jiangjing, Fu Yawei, Yang Jiahui, Wang Chunyang, Zhang Hui
The Gynecology Department, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Medicine (Baltimore). 2025 Apr 11;104(15):e40473. doi: 10.1097/MD.0000000000040473.
Since the advent of immunotherapy in clinical practice, it has profoundly transformed the paradigm of cancer treatment and has been rapidly adopted in clinical settings. Concurrently, the combination of immunotherapy with anti-angiogenic therapy has shown great promise in clinical research. The inevitable joint application brings about a greater number of adverse reactions. These adverse reactions are often perplexing, with the uncertainty of whether they stem from immunotherapy, anti-angiogenic therapy, or both. This is a case report of adverse reactions occurring when immune drugs and anti-vascular drugs are used together. This case is analyzed to provide a warning for adverse reactions in the clinical application of anti-angiogenic therapy combined with immunotherapy.
A 52-year-old cervical cancer patient with metastases had abdominal pain and fever post-treatment with bevacizumab, pembrolizumab, and chemotherapy, suggesting intestinal perforation.
After 2 chemotherapy cycles with bevacizumab and pembrolizumab, the patient had fever up to 39°C and abdominal pain. Exam showed tenderness, rigidity, and weak bowel sounds. Blood tests revealed leukocytosis and neutrophilia. Imaging indicated pneumoperitoneum and possible intestinal obstruction.
Emergency laparotomy revealed a small intestine perforation with strictures, leading to resection and ileostomy due to edema.
The postoperative recovery was good. We consider intestinal perforation caused by bevacizumab. Therefore, the patient was subsequently discontinued from bevacizumab and continued to receive paclitaxel, cisplatin and pembrolizumab. At present, the patient has finished chemotherapy and is receiving pembrolizumab maintenance therapy with no significant gastrointestinal adverse reactions.
Anti-angiogenic drugs and immunotherapy drugs each have their own side effects, and the occurrence of adverse reactions becomes more complex when used in combination. In the clinical process of combined medication, more attention should be paid to adverse reactions, early identification of severe adverse reactions, and active management.
自免疫疗法在临床实践中出现以来，它深刻地改变了癌症治疗模式，并在临床环境中迅速得到应用。同时，免疫疗法与抗血管生成疗法的联合在临床研究中显示出巨大的前景。不可避免的联合应用带来了更多的不良反应。这些不良反应常常令人困惑，不确定它们是源于免疫疗法、抗血管生成疗法，还是两者皆有。这是一篇关于免疫药物和抗血管药物联合使用时发生不良反应的病例报告。对该病例进行分析，为抗血管生成疗法联合免疫疗法的临床应用中的不良反应提供警示。
一名52岁的宫颈癌伴转移患者在接受贝伐单抗、帕博利珠单抗和化疗后出现腹痛和发热，提示肠道穿孔。
在接受2个周期的贝伐单抗和帕博利珠单抗化疗后，患者发热至39°C并伴有腹痛。检查显示有压痛、肌紧张和肠鸣音减弱。血液检查显示白细胞增多和中性粒细胞增多。影像学检查提示气腹和可能的肠梗阻。
急诊剖腹探查发现小肠穿孔并伴有狭窄，因水肿导致行小肠切除和回肠造口术。
术后恢复良好。我们认为肠道穿孔是由贝伐单抗引起的。因此，患者随后停用贝伐单抗，继续接受紫杉醇、顺铂和帕博利珠单抗治疗。目前，患者已完成化疗，正在接受帕博利珠单抗维持治疗，未出现明显的胃肠道不良反应。
抗血管生成药物和免疫治疗药物各自都有其副作用，联合使用时不良反应的发生变得更加复杂。在联合用药的临床过程中，应更加关注不良反应，早期识别严重不良反应并积极处理。
