Xin-Min Zhao1,2, Jing Zhao3, Xiang-Hua Wu1,2, Zhi-Guo Luo1,2, Hui-Jie Wang1,2, Hui Yu1,2, Jian-Hua Chang1,2, Jia-Lei Wang4,5. 1. Department of Medical Oncology, Fudan University Shanghai Cancer Center, No. 270 Dong-An Road, Shanghai, 200032, China. 2. Department of Oncology, Shanghai Medical College, Fudan University, No. 270 Dong-An Road, Shanghai, 200032, China. 3. Department of Medical Oncology, Shanghai Pulmonary Hospital Affiliated to Tongji University, Tongji University Medical School Cancer Institute, No. 507 Zhengmin Road, Shanghai, 200433, China. 4. Department of Medical Oncology, Fudan University Shanghai Cancer Center, No. 270 Dong-An Road, Shanghai, 200032, China. m18017312369@163.com. 5. Department of Oncology, Shanghai Medical College, Fudan University, No. 270 Dong-An Road, Shanghai, 200032, China. m18017312369@163.com.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
BACKGROUND: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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.