Yildiz Ibrahim
Department of Medical Oncology, Acibadem Mehmet Ali Aydinlar University Atakent Hospital, Istanbul, Turkey.
Case Rep Oncol. 2021 Feb 26;14(1):107-111. doi: 10.1159/000512829. eCollection 2021 Jan-Apr.
We report a patient with stage IV anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (primary lung signet ring cell adenocarcinoma) who received serial crizotinib, chemotherapy, and lorlatinib over more than 4 years. The patient discontinued crizotinib after approximately 4 months due to crizotinib-associated hepatotoxicity. Twenty-five days later, when transaminases had normalized, crizotinib was resumed. However, the patient's liver enzymes rapidly increased again, and crizotinib was discontinued. After 6 cycles of platinum-based chemotherapy, lorlatinib was initiated. Hepatotoxicity did not recur with lorlatinib, a next-generation ALK inhibitor, but grade 4 hypertriglyceridemia and acute pancreatitis were induced by lorlatinib after 4 months. To our knowledge, this is the first case report of acute pancreatitis with lorlatinib. Additionally, stereotactic body radiation therapy (SBRT) was performed for residual small primary lesions in the lung without stopping lorlatinib. Given the rarity of radiation pneumonitis, especially with the relatively small fields treated by SBRT, we suspect that lorlatinib enhanced the pulmonary toxicity. Physicians should be aware that ALK inhibitors, such as lorlatinib and crizotinib, have potentially lethal side effects.
我们报告了一名IV期间变性淋巴瘤激酶（ALK）重排的非小细胞肺癌患者（原发性肺印戒细胞腺癌），其在4年多的时间里接受了序贯克唑替尼、化疗和劳拉替尼治疗。该患者在大约4个月后因克唑替尼相关的肝毒性而停用克唑替尼。25天后，当转氨酶恢复正常时，重新开始使用克唑替尼。然而，患者的肝酶再次迅速升高，克唑替尼再次停用。在进行6个周期的铂类化疗后，开始使用劳拉替尼。作为新一代ALK抑制剂，劳拉替尼未再出现肝毒性，但4个月后引发了4级高甘油三酯血症和急性胰腺炎。据我们所知，这是首例使用劳拉替尼导致急性胰腺炎的病例报告。此外，在未停用劳拉替尼的情况下，对肺部残留的小原发灶进行了立体定向体部放射治疗（SBRT）。鉴于放射性肺炎罕见，尤其是SBRT治疗的野相对较小，我们怀疑劳拉替尼增强了肺部毒性。医生应意识到，劳拉替尼和克唑替尼等ALK抑制剂具有潜在的致命副作用。
