Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein/Utrecht, The Netherlands.
Department of Clinical Pharmacy, Division of Laboratories, Pharmacy and Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
Thorac Cancer. 2020 Dec;11(12):3634-3640. doi: 10.1111/1759-7714.13683. Epub 2020 Oct 19.
Platinum-based chemotherapy is currently the most frequently applied first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) without targetable mutations or high PD-L1 expression. Unfortunately, chemotherapy-induced toxicity is prevalent and may affect patients' quality of life to a considerable extent. Presumably, genetic variants of genes, coding for proteins involved in the processes of the development of toxicity, may be of interest as predictors of benefits and harms of platinum-based chemotherapy. The primary objective of the study is to investigate the influence of genetic variants on the incidence of chemotherapy-induced toxicity in patients with NSCLC undergoing first-line platinum-based chemotherapy. The main secondary objectives are to study the association between genetic variants and treatment response and to study the association between skeletal muscle mass (SMM) as well as patient-reported health-related quality of life (HRQOL) and treatment response and toxicity.
In this multicenter prospective follow-up study, a total of 350 patients with NSCLC (stage II-IV) undergoing first-line platinum-based chemotherapy will be included. Blood samples for DNA isolation and genotyping, questionnaires and data on patients risk factors and disease stage will be recorded. The primary endpoint is chemotherapy-induced (non-)hematological toxicity, comprising; nephrotoxicity, neuropathy, esophagitis, ototoxicity, pneumonitis, gastrointestinal toxicity, anemia, leukocytopenia, neutropenia and thrombocytopenia. Secondary endpoints include dose-limiting toxicity, HRQOL, and treatment response (radiological response [RECIST 1.1] and overall survival [OS]).
Results of the PGxLUNG study will be primarily used to determine the influence of genetic variants on the incidence of chemotherapy-induced toxicity in patients with NSCLC undergoing first-line platinum-based chemotherapy.
铂类化疗目前是无靶向突变或高 PD-L1 表达的晚期非小细胞肺癌（NSCLC）患者最常应用的一线治疗方法。不幸的是，化疗诱导的毒性很常见，可能在相当大的程度上影响患者的生活质量。推测，编码毒性发生过程中涉及的蛋白质的基因的遗传变异可能是预测铂类化疗的获益和危害的有用指标。该研究的主要目的是研究遗传变异对接受一线铂类化疗的 NSCLC 患者化疗诱导毒性发生率的影响。主要次要目的是研究遗传变异与治疗反应之间的关系，以及研究骨骼肌质量（SMM）以及患者报告的健康相关生活质量（HRQOL）与治疗反应和毒性之间的关系。
在这项多中心前瞻性随访研究中，将纳入 350 名接受一线铂类化疗的 NSCLC（II-IV 期）患者。将记录用于 DNA 分离和基因分型的血液样本、问卷以及患者危险因素和疾病分期的数据。主要终点是化疗诱导的（非）血液学毒性，包括肾毒性、神经病变、食管炎、耳毒性、肺炎、胃肠道毒性、贫血、白细胞减少症、中性粒细胞减少症和血小板减少症。次要终点包括剂量限制毒性、HRQOL 和治疗反应（影像学反应[RECIST 1.1]和总生存期[OS]）。
PGxLUNG 研究的结果将主要用于确定遗传变异对接受一线铂类化疗的 NSCLC 患者化疗诱导毒性发生率的影响。
