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BRAF 和 MEK 抑制剂致 BRAF V600E 突变型非小细胞肺癌相关药物性结肠炎:病例报告。

Drug-induced colitis on BRAF and MEK inhibitors for BRAF V600E-mutated non-small cell lung cancer: a case report.

机构信息

Medical Oncology Unit, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy.

Department of Specialized, Experimental and Diagnostic Medicine, University of Bologna, Bologna, Italy.

出版信息

Invest New Drugs. 2022 Feb;40(1):190-193. doi: 10.1007/s10637-021-01166-7. Epub 2021 Aug 26.

Abstract

INTRODUCTION

The combination of BRAF and MEK inhibitors has deeply changed the treatment of BRAF V600-mutant non-small cell lung cancer patients. These agents demonstrated high antitumor activity as well as safe and manageable toxicity profile. Hypertension, pyrexia and increased liver enzymes are the most common adverse events. Gastrointestinal toxicities are rare, and mainly consist of mild grade vomiting and diarrhea.

CASE REPORT

We report the case of 70-year-old man affected by BRAF V600-mutant NSCLC with bilateral lung and bone metastases. First-line treatment with encorafenib (450 mg once daily) and binimetinib (45 mg twice daily) was administered within a clinical trial. At the first radiological assessment, computed tomography (CT) scan showed a partial response and signs of intestinal inflammation were reported. The investigational treatment was timely withheld. The subsequent colonoscopy demonstrated the presence of ulcerative lesions at the caecal tract, and the histological diagnosis suggested a drug-induced colitis. No specific treatment was given as the patient did not report abdominal disturbances. Forty-five days after treatment interruption a new CT scan showed the resolution of bowel inflammation and investigational treatment was resumed at the same doses. The patient is still alive and free of toxicity recurrence after 11 months from treatment initiation. Conclusion. Severe gastrointestinal toxicities are uncommon with BRAF and MEK inhibitors, although cases of colitis and intestinal perforation have already been reported in literature. The pathogenesis seems to be related to the MAPK pathway inhibition performed by MEK inhibitors. These adverse events should be accounted given the potential to evolve into life-threatening conditions.

摘要

介绍

BRAF 和 MEK 抑制剂的联合应用深刻改变了 BRAF V600 突变型非小细胞肺癌患者的治疗模式。这些药物具有高抗肿瘤活性,同时具有安全且可管理的毒性特征。高血压、发热和肝酶升高是最常见的不良反应。胃肠道毒性罕见,主要为轻度呕吐和腹泻。

病例报告

我们报告了一例 70 岁男性 BRAF V600 突变型非小细胞肺癌患者,该患者存在双肺和骨转移。在临床试验中,给予患者 encorafenib(450mg,每日一次)和 binimetinib(45mg,每日两次)一线治疗。首次影像学评估时,计算机断层扫描(CT)显示部分缓解,并报告存在肠道炎症迹象。及时停用了研究性治疗。随后的结肠镜检查显示盲肠部位存在溃疡性病变,组织学诊断提示药物诱导性结肠炎。由于患者未报告腹部不适,未给予特定治疗。治疗中断 45 天后,新的 CT 扫描显示肠道炎症已缓解,恢复相同剂量的研究性治疗。自治疗开始后 11 个月,患者仍然存活且无毒性复发。

结论

BRAF 和 MEK 抑制剂罕见出现严重胃肠道毒性,但文献中已报道过结肠炎和肠穿孔病例。发病机制似乎与 MEK 抑制剂抑制 MAPK 通路有关。应考虑这些不良反应,因为它们有可能发展为危及生命的情况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c15/8763820/aaeda800c581/10637_2021_1166_Fig1_HTML.jpg

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