Department of Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
Department of Pulmonary Medicine, Amphia Hospital, Breda, the Netherlands.
Thorax. 2021 Nov;76(11):1150-1153. doi: 10.1136/thoraxjnl-2020-216504. Epub 2021 Apr 15.
Patients with advanced non-small-cell lung cancer who are treated with pemetrexed display a wide variation in clinical response and toxicity. In this prospective, multicentre cohort study, we investigated the association with treatment effectiveness and toxicity of 10 polymorphisms in nine candidate genes, covering the folate pathway (), cell transport (), intracellular metabolism () and target enzymes () of pemetrexed. Adjusted for sex, ECOG performance score and disease stage, the association between (rs12995526) and overall survival (HR 1.59, 95% CI 1.06 to 2.39) was significant. Regarding toxicity, this polymorphism was significantly associated with severe laboratory (p=0.014) and clinical (p=0.016) chemotherapy-related adverse events, severe neutropenia (p=0.007) and all-grade diarrhoea (p=0.034) in multivariable analyses.
接受培美曲塞治疗的晚期非小细胞肺癌患者在临床反应和毒性方面存在很大差异。在这项前瞻性、多中心队列研究中，我们研究了 9 个候选基因中的 10 个多态性与培美曲塞治疗效果和毒性的相关性，这些基因涵盖了叶酸途径（）、细胞转运（）、细胞内代谢（）和培美曲塞的靶酶（）。调整性别、ECOG 表现评分和疾病分期后， （rs12995526）与总生存期（HR1.59，95%CI1.06-2.39）之间存在显著关联。关于毒性，该 多态性与严重的实验室（p=0.014）和临床（p=0.016）化疗相关不良事件、严重中性粒细胞减少症（p=0.007）和所有级别腹泻（p=0.034）显著相关。
