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Significance of glucocorticoid receptor expression in patients with non-small cell lung cancer treated with pemetrexed-based chemotherapy

  • Clinical Trial Report
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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.

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Abbreviations

non-sq-NSCLC:

Non-small cell lung cancer glucocorticoid receptor

PBMC:

Peripheral blood mononuclear cells

PFS:

Progression-free survival

OS:

Overall survival

mPFS:

Median PFS

mOS:

Median OS

CI:

Confidence interval

PCFT:

Proton-coupled folate transporter

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Authors and Affiliations

  1. Department of Medical Oncology, Fudan University Shanghai Cancer Center, No. 270 Dong-An Road, Shanghai, 200032, China

    Xin-min Zhao, Xiang-hua Wu, Zhi-guo Luo, Hui-jie Wang, Hui Yu, Jian-hua Chang & Jia-lei Wang

  2. Department of Oncology, Shanghai Medical College, Fudan University, No. 270 Dong-An Road, Shanghai, 200032, China

    Xin-min Zhao, Xiang-hua Wu, Zhi-guo Luo, Hui-jie Wang, Hui Yu, Jian-hua Chang & Jia-lei Wang

  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

    Jing Zhao

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  1. Xin-min Zhao
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Contributions

WJL and ZXM conceived the study idea. ZXM and WXH involved in conducting the molecular studies. ZXM, ZJ, LZG, WHJ, YH, and CJH involved in interpretation of the histological data. ZXM, ZJ,and WJL were involved in preparation of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jia-lei Wang.

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Funding

This study was funded by the National Natural Science Foundation of China (No. 81302009 and 81401892), Shanghai Municipal Commission of Health and Family Planning (No. 201440423), Shanghai Science and Technology Committee Natural Science Foundation (No. 12ZR1406400), and Clinical Research Funds of Wu Jieping Medical Foundation (No.320.6750.14278).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Zhao, Xm., Zhao, J., Wu, Xh. et al. Significance of glucocorticoid receptor expression in patients with non-small cell lung cancer treated with pemetrexed-based chemotherapy. Cancer Chemother Pharmacol 80, 851–860 (2017). https://doi.org/10.1007/s00280-017-3399-1

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  • DOI: https://doi.org/10.1007/s00280-017-3399-1

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