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Quantification of circulating endothelial cells as a predictor of response to chemotherapy with platinum and pemetrexed in patients with advanced non-squamous non-small cell lung carcinoma

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Abstract

Introduction

Circulating endothelial cells (CEC) play an important role in tumor neovascularization and may have prognostic value in cancer patients. This study was designed to investigate the role of CEC as a marker for predicting platinum plus pemetrexed first-line chemotherapy efficacy in advanced non-squamous non-small cell lung cancer (NSCLC).

Methods

A prospective study was performed whose main objective was to study whether the numbers of CEC at baseline and prior to the second and third cycle of chemotherapy were response predictors. Sixty-nine patients received cisplatin plus pemetrexed, and peripheral blood samples were performed at baseline and after second and third cycle. Separation and CEC count were performed using inmunomagnetic separation (CellSearch).

Results

The CEC count in 4 mL of peripheral blood was obtained prior to the first, second, and third cycle of treatment. Baseline levels and evolution of CEC were correlated with response to treatment according to RECIST criteria after three cycles of treatment. Sixty-nine patients were included: 43 (64.2 %) received cisplatin/pemetrexed and 24 (35.8 %) carboplatin/pemetrexed. Range of baseline CEC: 8–965 (mean of 153 cel/4 mL). The results after 3 cycles were: 25 partial responses (36.2 %), 17 cases of stabilization of disease (24.6 %), 16 of progressive disease (23.2 %) and 11 non-evaluables (16 %). No significant relationship between the baseline CEC count and response was found (p value = 0.831). Increase >50 % between the first and second cycle was correlated significantly with progression disease (p = 0.008). Patients who had a baseline CEC count greater than the mean (>153 cells/4 mL) showed longer progression-free survival and global survival without statistical significance.

Conclusions

In this homogeneous group of patients with NSCLC, there is no correlation between response to treatment and CEC baseline levels. The increase in CEC numbers after the first cycle could be a negative predictive factor.

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Acknowledgments

Funding for this study was provided by Eli Lilly and Company; Eli Lilly and Company as such had no role in data collection, analysis or evaluation. CRO Pivotal provided advice to properly handle and submit the paper. Kavita Gandhi has reviewed and edited the manuscript language.

Conflict of interest

None author has any actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations that could inappropriately influence (bias) their work.

Ethical standard

Ethics committees have been informed regarding all of this study procedures. Patients were properly informed and signed an informed consent.

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Correspondence to Alfredo Sánchez Hernández.

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On behalf of Grup ďinvestigació i divulgació en Oncologia (GIDO).

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Sánchez Hernández, A., José Juan, O., Vidal Martínez, J. et al. Quantification of circulating endothelial cells as a predictor of response to chemotherapy with platinum and pemetrexed in patients with advanced non-squamous non-small cell lung carcinoma. Clin Transl Oncol 17, 281–288 (2015). https://doi.org/10.1007/s12094-014-1223-5

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  • DOI: https://doi.org/10.1007/s12094-014-1223-5

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