Department of Thoracic Oncology, Osaka International Cancer Institute, 3-1-69 Otemachi Chuo-ku, Osaka, 541-8567, Japan.
Department of Thoracic Malignancy, Osaka Habikino Medical Center, Habikino, Japan.
Invest New Drugs. 2018 Aug;36(4):696-701. doi: 10.1007/s10637-018-0581-1. Epub 2018 Mar 14.
Background Bevacizumab (Bev) is generally well-tolerated, and Bev-associated intestinal perforation (BAP) is a rare albeit serious side effect in cases of non-small cell lung cancer (NSCLC). Therefore, the present study aimed to identify clinical predictors of BAP to help predict and manage the development of life-threatening intestinal complications among patients receiving Bev. Methods This retrospective study evaluated demographic, clinical, and treatment factors for patients with NSCLC who were treated with Bev between February 2010 and August 2015 at our center. Results We identified 314 regimens (208 patients; median age: 65 years; 115 women) for analysis, which included 119 first-line regimens, 74 s-line regimens, and 121 third-line or later regimens. BAP occurred in 7 cases (2.23% among all regimens and 3.37% among all patients), which generally occurred during first- or second-line treatment and was caused by ulcerative colitis (1 case), colon diverticulitis (1 case), and idiopathic perforations (5 cases). Univariate analyses revealed that BAP was significantly associated with deteriorating PS during the first cycle of chemotherapy (odd ratio [OR]: 11.07, 95% confidence interval [CI]: 2.37-51.63, p = 0.0022), grade ≥ 3 diarrhea (OR: 11.37, 95% CI: 2.37-54.50, p = 0.0024), febrile neutropenia (OR: 9.16, 95% CI: 1.98-42.49, p = 0.0047), and stomatitis (OR: 4.60, 95% CI: 1.01-21.04, p = 0.0492). Conclusions Among patients with NSCLC, BAP was associated with deteriorating PS during the first cycle of chemotherapy, grade ≥ 3 diarrhea, febrile neutropenia, and stomatitis. Therefore, careful observation is needed for patients with NSCLC who receive Bev in any line of treatment, especially if they develop serious side effects that affect their PS or mucous membrane.
贝伐单抗(Bev)通常具有良好的耐受性,在非小细胞肺癌(NSCLC)患者中,贝伐单抗相关的肠穿孔(BAP)是一种罕见但严重的副作用。因此,本研究旨在确定 BAP 的临床预测因子,以帮助预测和管理接受贝伐单抗治疗的患者发生危及生命的肠道并发症。
本回顾性研究评估了 2010 年 2 月至 2015 年 8 月在本中心接受贝伐单抗治疗的 NSCLC 患者的人口统计学、临床和治疗因素。
我们共确定了 314 个方案(208 例患者;中位年龄:65 岁;115 例女性)进行分析,其中包括 119 个一线方案、74 个二线方案和 121 个三线或更后线方案。7 例(所有方案的 2.23%,所有患者的 3.37%)发生 BAP,通常发生在一线或二线治疗期间,病因分别为溃疡性结肠炎(1 例)、结肠憩室炎(1 例)和特发性穿孔(5 例)。单因素分析显示,BAP 与化疗第一周期 PS 恶化(比值比 [OR]:11.07,95%置信区间 [CI]:2.37-51.63,p=0.0022)、≥3 级腹泻(OR:11.37,95%CI:2.37-54.50,p=0.0024)、发热性中性粒细胞减少症(OR:9.16,95%CI:1.98-42.49,p=0.0047)和口腔炎(OR:4.60,95%CI:1.01-21.04,p=0.0492)显著相关。
在 NSCLC 患者中,BAP 与化疗第一周期 PS 恶化、≥3 级腹泻、发热性中性粒细胞减少症和口腔炎有关。因此,对于接受任何线治疗的 NSCLC 患者,尤其是出现影响 PS 或黏膜的严重不良反应的患者,需要密切观察。