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Thymidylate synthase expression as a predictive biomarker of pemetrexed sensitivity in advanced non-small cell lung cancer.

Chamizo C, Zazo S, Dómine M, Cristóbal I, García-Foncillas J, Rojo F, Madoz-Gúrpide J - BMC Pulm Med (2015)

Bottom Line: Although it has been suggested that a high level of thymidylate synthase (TYMS) gene expression in malignant tumors is related to reduced sensitivity to the antifolate drug pemetrexed, no direct evidence for such an association has been demonstrated in routine clinical samples from patients treated with the drug.The response rate for patients with low TYMS expression was 0.29 compared with 0.03 in patients with overexpression (P = 0.025).A significant benefit was observed in patients with low expression both in time to progression (average TTP = 56 vs. 23 months, P = 0.001) and in overall survival (average OS = 60 vs. 25 months, P = 0.002).

View Article: PubMed Central - PubMed

Affiliation: Cancer Biomarkers Research Group, Fundacion Jimenez Diaz University Hospital Health Research Institute, UAM, Madrid, Spain. cristina.chamizo@fjd.es.

ABSTRACT

Background: Although it has been suggested that a high level of thymidylate synthase (TYMS) gene expression in malignant tumors is related to reduced sensitivity to the antifolate drug pemetrexed, no direct evidence for such an association has been demonstrated in routine clinical samples from patients treated with the drug. The purpose of this study was to quantitatively assess the impact of TYMS gene expression in tumor cells as a predictor of the efficacy of pemetrexed therapy in patients with advanced non-small cell lung cancer (NSCLC) treated at our institution.

Methods: Sixty-two NSCLC patients were included in this study: 16 patients received platins-pemetrexed as first-line NSCLC, and 46 pemetrexed in monotherapy as second- or subsequent-line treatment. Total mRNA was isolated and the expression of TYMS was analyzed by RT-qPCR. TYMS levels were calibrated against expression in normal lung tissue.

Results: TYMS overexpression was detected in 61 % of patients and low expression in 39 %. The response rate for patients with low TYMS expression was 0.29 compared with 0.03 in patients with overexpression (P = 0.025). A significant benefit was observed in patients with low expression both in time to progression (average TTP = 56 vs. 23 months, P = 0.001) and in overall survival (average OS = 60 vs. 25 months, P = 0.002).

Conclusions: TYMS overexpression in tumor cells correlated with a reduced response to pemetrexed-containing chemotherapy and might be used as a predictive biomarker in advanced NSCLC patients.

No MeSH data available.


Related in: MedlinePlus

a Significant clinical-pathological correlations for TYMS expression in NSCLC patients. With respect to the type of response, tumors were categorized as either responding (CR, complete response or PR, partial response) or non-responding (SD, stable disease or PD, progressive disease). b Close-to-significance correlations
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Fig2: a Significant clinical-pathological correlations for TYMS expression in NSCLC patients. With respect to the type of response, tumors were categorized as either responding (CR, complete response or PR, partial response) or non-responding (SD, stable disease or PD, progressive disease). b Close-to-significance correlations

Mentions: The clinical characteristics of the patients are shown in Table 1. TYMS gene-overexpression analysis was performed in 62 cases for which complete clinical records were available. This analysis showed significant correlation with progression (P = 0.003) and response to pemetrexed (P = 0.025) (Fig. 2a). We categorized the tumors as either responding or non-responding. The non-responding group showed significantly higher levels of TYMS expression as compared to the responding group. TYMS overexpression analysis also showed a tendency toward correlation between overexpression smoking (P = 0.056) and histology (P = 0.071) (Fig. 2b), but was not associated with gender, performance status, or line of treatment.Table 1


Thymidylate synthase expression as a predictive biomarker of pemetrexed sensitivity in advanced non-small cell lung cancer.

Chamizo C, Zazo S, Dómine M, Cristóbal I, García-Foncillas J, Rojo F, Madoz-Gúrpide J - BMC Pulm Med (2015)

a Significant clinical-pathological correlations for TYMS expression in NSCLC patients. With respect to the type of response, tumors were categorized as either responding (CR, complete response or PR, partial response) or non-responding (SD, stable disease or PD, progressive disease). b Close-to-significance correlations
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC4623912&req=5

Fig2: a Significant clinical-pathological correlations for TYMS expression in NSCLC patients. With respect to the type of response, tumors were categorized as either responding (CR, complete response or PR, partial response) or non-responding (SD, stable disease or PD, progressive disease). b Close-to-significance correlations
Mentions: The clinical characteristics of the patients are shown in Table 1. TYMS gene-overexpression analysis was performed in 62 cases for which complete clinical records were available. This analysis showed significant correlation with progression (P = 0.003) and response to pemetrexed (P = 0.025) (Fig. 2a). We categorized the tumors as either responding or non-responding. The non-responding group showed significantly higher levels of TYMS expression as compared to the responding group. TYMS overexpression analysis also showed a tendency toward correlation between overexpression smoking (P = 0.056) and histology (P = 0.071) (Fig. 2b), but was not associated with gender, performance status, or line of treatment.Table 1

Bottom Line: Although it has been suggested that a high level of thymidylate synthase (TYMS) gene expression in malignant tumors is related to reduced sensitivity to the antifolate drug pemetrexed, no direct evidence for such an association has been demonstrated in routine clinical samples from patients treated with the drug.The response rate for patients with low TYMS expression was 0.29 compared with 0.03 in patients with overexpression (P = 0.025).A significant benefit was observed in patients with low expression both in time to progression (average TTP = 56 vs. 23 months, P = 0.001) and in overall survival (average OS = 60 vs. 25 months, P = 0.002).

View Article: PubMed Central - PubMed

Affiliation: Cancer Biomarkers Research Group, Fundacion Jimenez Diaz University Hospital Health Research Institute, UAM, Madrid, Spain. cristina.chamizo@fjd.es.

ABSTRACT

Background: Although it has been suggested that a high level of thymidylate synthase (TYMS) gene expression in malignant tumors is related to reduced sensitivity to the antifolate drug pemetrexed, no direct evidence for such an association has been demonstrated in routine clinical samples from patients treated with the drug. The purpose of this study was to quantitatively assess the impact of TYMS gene expression in tumor cells as a predictor of the efficacy of pemetrexed therapy in patients with advanced non-small cell lung cancer (NSCLC) treated at our institution.

Methods: Sixty-two NSCLC patients were included in this study: 16 patients received platins-pemetrexed as first-line NSCLC, and 46 pemetrexed in monotherapy as second- or subsequent-line treatment. Total mRNA was isolated and the expression of TYMS was analyzed by RT-qPCR. TYMS levels were calibrated against expression in normal lung tissue.

Results: TYMS overexpression was detected in 61 % of patients and low expression in 39 %. The response rate for patients with low TYMS expression was 0.29 compared with 0.03 in patients with overexpression (P = 0.025). A significant benefit was observed in patients with low expression both in time to progression (average TTP = 56 vs. 23 months, P = 0.001) and in overall survival (average OS = 60 vs. 25 months, P = 0.002).

Conclusions: TYMS overexpression in tumor cells correlated with a reduced response to pemetrexed-containing chemotherapy and might be used as a predictive biomarker in advanced NSCLC patients.

No MeSH data available.


Related in: MedlinePlus