Department of Respiratory Medicine, Lihuili Hospital, Ningbo Medical Center, No. 57, Xin'ning Road, Ningbo, 315041, China.
Department of Radiation Oncology, Lihuili Hospital, Ningbo Medical Center, Ningbo, 315041, China.
BMC Pulm Med. 2018 Jul 20;18(1):121. doi: 10.1186/s12890-018-0682-9.
Crizotinib is a multi-target inhibitor approved for the treatment of advanced non-small-cell lung cancer patients with a ROS1 rearrangement. However, interstitial lung disease is a rare but severe and fatal side effect of crizotinib that should lead to immediate discontinuation of the drug. Unfortunately, the pathophysiology, molecular mechanism and risk factors for crizotinib-induced interstitial lung disease remain poorly understood.
We first identified and reported interstitial lung disease induced de novo by crizotinib in a 47-year-old female patient who was diagnosed with advanced lung adenocarcinoma with a ROS1 rearrangement in a malignant pleural effusion. Subsequent next-generation sequencing analysis revealed both ROS1 rearrangement and an EGFR exon 19 deletion mutation in lung biopsy specimens, which were histologically confirmed to be interstitial lung disease. Although crizotinib treatment was ceased immediately and a shock treatment with high-dose methylprednisolone as well as other necessary treatment procedures was applied to reverse the interstitial lung disease process, the patient died.
The present case indicates that while treating non-small-cell lung cancer patients with crizotinib, it is important to constantly monitor any newly emerging respiratory symptoms and unexplained imaging changes, which may suggest an adverse effect related to drug-induced interstitial lung disease or even lethality. Histopathology and molecular pathological examination of lung biopsy specimens may help clinicians understand the development mechanism and exclude other causes.
克唑替尼是一种多靶点抑制剂，获批用于治疗 ROS1 重排的晚期非小细胞肺癌患者。然而，间质性肺病是克唑替尼罕见但严重且致命的副作用，应立即停止使用该药。不幸的是，克唑替尼诱导的间质性肺病的病理生理学、分子机制和危险因素仍知之甚少。
我们首先在一名 47 岁女性患者中发现并报告了由克唑替尼引起的新发间质性肺病，该患者在恶性胸腔积液中被诊断为晚期肺腺癌，存在 ROS1 重排。随后的下一代测序分析显示，肺活检标本中均存在 ROS1 重排和 EGFR 外显子 19 缺失突变，组织学证实为间质性肺病。尽管立即停止了克唑替尼治疗，并应用大剂量甲基强的松龙进行休克治疗以及其他必要的治疗措施来逆转间质性肺病进程，但患者仍死亡。
本病例表明，在使用克唑替尼治疗非小细胞肺癌患者时，重要的是要持续监测任何新出现的呼吸道症状和无法解释的影像学变化，这可能提示与药物诱导的间质性肺病相关的不良反应，甚至是致命性的。肺活检标本的组织病理学和分子病理学检查有助于临床医生了解发病机制，并排除其他原因。
