Ceritinib 可长期控制病情:临床观察

E. Reutova, K. Laktionov, M. A. Ardzinba
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摘要

ALK阳性非小细胞肺癌是展示精准医疗成功的绝佳模型。一种罕见的遗传性疾病--无性大细胞淋巴瘤基因重排,发生率为5%-7%,形成了患者特定的临床和形态特征。在 ALK 阳性的非小细胞肺癌中,脑部是一个常见的转移目标。尽管预后不良,但药物抗肿瘤治疗在这类非小细胞肺癌患者中取得的成就尤为显著--持续使用几代ALK抑制剂可使患者的中位总生存期达到约80个月。在俄罗斯联邦,有 4 种药物被批准用于治疗 ALK 阳性的非小细胞肺癌。其中一种是第二代 ALK 抑制剂--色瑞替尼,目前正积极用于一线治疗和克唑替尼治疗进展后的治疗。在 ASCEND-4 登记研究中,使用 Ceritinib 的中位进展时间是标准多化疗的两倍。然而,该药的初始日剂量为750毫克,会引起严重的胃肠道和肝脏毒性。后来,药物剂量减少到 450 毫克,治疗的耐受性明显改善,疗效却没有降低。下面介绍的临床病例表明,现代靶向疗法可以长期控制转移性ALK阳性非小细胞肺癌的病情。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Ceritinib as a long-term disease control: Clinical observation
ALK-positive non-small cell lung cancer is an excellent model demonstrating the success of precision medicine. A rare genetic disorder – a rearrangement of the anaplastic large cell lymphoma gene, occurring with a frequency of 5–7%, forms a certain clinical and morphological portrait of the patient. In ALK-positive non-small cell lung cancer, the brain is a frequent target for metastasis. But despite this negative prognosis factor, it is in this cohort of non-small cell lung cancer patients that the achievements of drug antitumor therapy are especially significant – the consistent use of ALK inhibitors of several generations allows to achieve a median overall survival of about 80 months. In the Russian Federation, 4 drugs have been approved for the treatment of ALK-positive non-small cell lung cancer. One of them is a second–generation ALK inhibitor – ceritinib is actively used both in the first line of therapy and after progression on crizotinib. In the ASCEND-4 registration study, the median time to progression on ceritinib was twice as long as on standard polychemotherapy. However, the initial daily dose of the drug 750 mg was associated with severe gastrointestinal and hepatotoxicity. Subsequently, the dose of the drug was reduced to 450 mg, which significantly improved the tolerability of treatment without reducing its effectiveness. The clinical case presented below demonstrates the possibility of modern targeted therapy to provide long-term disease control in metastatic ALK-positive nonsmall cell lung cancer.
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