Zhao Xin-Min, Zhao Jing, Wu Xiang-Hua, Luo Zhi-Guo, Wang Hui-Jie, Yu Hui, Chang Jian-Hua, Wang Jia-Lei
Department of Medical Oncology, Fudan University Shanghai Cancer Center, No. 270 Dong-An Road, Shanghai, 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, No. 270 Dong-An Road, Shanghai, 200032, China.
Cancer Chemother Pharmacol. 2017 Oct;80(4):851-860. doi: 10.1007/s00280-017-3399-1. Epub 2017 Jul 28.
Pemetrexed is the preferred chemotherapy agent in the management of non-squamous non-small cell lung cancer (non-sq-NSCLC), but lacks biomarkers predicting its efficacy. Dexamethasone, one of the premedications of pemetrexed, may downregulate p53 through the glucocorticoid receptor (GR). The purpose of our study was to explore the effect of GR in peripheral blood mononuclear cells (PBMC) and its role in predicting pemetrexed efficacy.
In all, 122 patients with stage IV non-sq-NSCLC who received first-line pemetrexed-containing chemotherapy were retrospectively reviewed. The expression of GR in PBMC was measured before treatment with pemetrexed using real-time PCR was used to detect the levels of GRα and GRβ.
The response rate for all patients was 38.5%, with a median progression-free survival (PFS) of 5.9 months and overall survival (OS) of 14.3 months. In univariate analyses, patients with a low GRα/GRβ ratio in PBMC had higher RR, better PFS, and better OS than those with a high GRα/GRβ ratio (RR: 48.2 vs. 30.3%, p = 0.043; mPFS: 6.9 vs. 4.0 months, p < 0.001; mOS: 18.7 vs. 12.2 months, p = 0.005). The baseline GRα/GRβ ratio was an independent factor for RR (odds ratio [OR] = 0.451, 95% CI 0.208-0.978; p = 0.044), PFS (HR = 1.584, 95% CI 1.094-2.295; p = 0.015), and OS (HR = 1.761, 95% CI 1.195-2.595; p = 0.004).
Baseline GRα/GRβ ratio in PBMC may play a role in predicting the efficacy of first-line pemetrexed-containing chemotherapy in stage IV non-sq NSCLC patients.
培美曲塞是治疗非鳞状非小细胞肺癌（non-sq-NSCLC）的首选化疗药物，但缺乏预测其疗效的生物标志物。地塞米松是培美曲塞的预处理药物之一，可能通过糖皮质激素受体（GR）下调p53。本研究的目的是探讨GR在外周血单个核细胞（PBMC）中的作用及其在预测培美曲塞疗效中的作用。
回顾性分析122例接受含培美曲塞一线化疗的IV期non-sq-NSCLC患者。在培美曲塞治疗前，采用实时PCR检测PBMC中GR的表达，以检测GRα和GRβ的水平。
所有患者的缓解率为38.5%，中位无进展生存期（PFS）为5.9个月，总生存期（OS）为14.3个月。在单因素分析中，PBMC中GRα/GRβ比值低的患者比GRα/GRβ比值高的患者具有更高的缓解率、更好的PFS和更好的OS（缓解率：48.2%对30.3%，p = 0.043；中位PFS：6.9个月对4.0个月，p < 0.001；中位OS：18.7个月对12.2个月，p = 0.005）。基线GRα/GRβ比值是缓解率（比值比[OR]=0.451，95%可信区间0.208-0.978；p = 0.044）、PFS（风险比[HR]=1.584，95%可信区间1.094-2.295；p = 0.015）和OS（HR=1.761，95%可信区间1.195-2.595；p = 0.004）的独立因素。
PBMC中的基线GRα/GRβ比值可能在预测IV期non-sq NSCLC患者含培美曲塞一线化疗的疗效中发挥作用。
