Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-Minamimachi, Chuo-Ku, Kobe, 650-0047, Japan.
Department of Diagnostic Pathology, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-Minamimachi, Chuo-Ku, Kobe, 650-0047, Japan.
Invest New Drugs. 2021 Dec;39(6):1702-1706. doi: 10.1007/s10637-021-01135-0. Epub 2021 May 23.
Gastrointestinal perforation related to mitogen-activated protein kinase kinase (MEK) inhibitors has been reported previously; however, there has been no case report of such a condition in patients with non-small cell lung cancer (NSCLC). Herein, we report a case of small intestinal perforation secondary to dabrafenib and trametinib administration, but not related to tumor regression. A 62-year-old man with non-small cell lung cancer harboring BRAF V600E mutation was treated with dabrafenib and trametinib. Four months after the initiation of treatment, a small intestinal perforation was diagnosed. Dabrafenib and trametinib rechallenge was performed after gastrointestinal perforation. The patient responded well to therapy and did not experience recurrence of gastrointestinal perforation. To the best of our knowledge, this is the first report of gastrointestinal perforation in a patient with NSCLC treated with a MEK inhibitor. The mechanism and risk factors of trametinib-induced perforation are currently unknown. Physicians should be aware of such severe gastrointestinal side effects of trametinib.
先前已有文献报道与丝裂原活化蛋白激酶激酶（MEK）抑制剂相关的胃肠道穿孔；然而，在非小细胞肺癌（NSCLC）患者中尚未有此类情况的病例报告。在此，我们报告一例继发于达拉非尼和曲美替尼治疗的小肠穿孔，但与肿瘤退缩无关。一名 62 岁男性，患有携带 BRAF V600E 突变的非小细胞肺癌，接受达拉非尼和曲美替尼治疗。治疗开始后 4 个月，诊断为小肠穿孔。在发生胃肠道穿孔后再次使用达拉非尼和曲美替尼。患者对治疗反应良好，未再次发生胃肠道穿孔。据我们所知，这是首例报道的 NSCLC 患者使用 MEK 抑制剂后发生胃肠道穿孔。曲美替尼诱导穿孔的机制和危险因素目前尚不清楚。医生应注意曲美替尼的这种严重胃肠道副作用。
