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Clinical significance of topoisomerase-II expression in patients with advanced non-small cell lung cancer treated with amrubicin.

ABSTRACT: BACKGROUND:Amrubicin chemotherapy is a treatment option for patients with non-small cell lung cancer (NSCLC) after third-line treatment in Japan. Although topoisomerase-II (Topo-II), a target of amrubicin, has been reported to be a prognostic or predictive marker for chemosensitivity and clinical outcomes in various types of malignancies, its effects in the Japanese population remain unknown. METHODS:Data regarding 44 patients with advanced NSCLC treated with amrubicin between April 2004 and May 2014 were retrospectively analyzed. We evaluated the expression levels of Topo-II by immunohistochemical staining of tumor specimens obtained via biopsy or surgical resection. RESULTS:The majority of enrolled patients were men (68%) with a median age of 67 (range, 43-78) years. The most common histological type was adenocarcinoma (70%). High Topo-II expression was observed in 13 (30%) of the 44 patients. The median progression-free survival and overall survival (OS) durations were 1.8 and 8.8 months, respectively. While there was no significant association between Topo-II expression and progression-free survival, patients with low Topo-II expression had significantly longer OS than did those with high Topo-II expression. Good performance status and low expression of Topo-II were all significantly associated with a favorable OS. CONCLUSION:Low expression of Topo-II was identified as an independent prognostic factor for longer survival in patients with NSCLC receiving amrubicin, a Topo-II inhibitor. KEY POINTS:Significant findings of the study The median progression-free survival and overall survival (OS) durations were 1.8 and 8.8 months, respectively. While there was no significant association between Topo-II expression and progression-free survival, patients with low Topo-II expression had significantly longer OS than did those with high Topo-II expression. Good performance status and low expression of Topo-II were all significantly associated with a favorable OS. What this study adds This study is the first to assess the effects of topoisomerase-II (Topo-II), a target of amrubicin, as a prognostic or predictive marker for chemosensitivity and clinical outcomes in the Japanese population.

SUBMITTER: Sakurai R

PROVIDER: S-EPMC6997014 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Clinical significance of topoisomerase-II expression in patients with advanced non-small cell lung cancer treated with amrubicin.

Sakurai Reiko R Kaira Kyoichi K Miura Yosuke Y Sunaga Noriaki N Saito Ryusei R Oyama Tetsunari T Hisada Takeshi T Yamada Masanobu M

Thoracic cancer 20200103 2

<h4>Background</h4>Amrubicin chemotherapy is a treatment option for patients with non-small cell lung cancer (NSCLC) after third-line treatment in Japan. Although topoisomerase-II (Topo-II), a target of amrubicin, has been reported to be a prognostic or predictive marker for chemosensitivity and clinical outcomes in various types of malignancies, its effects in the Japanese population remain unknown.<h4>Methods</h4>Data regarding 44 patients with advanced NSCLC treated with amrubicin between Apr ...[more]

PMID: 31901017

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Project description:BackgroundBevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF)-A, has shown efficacy in patients with advanced nonsquamous non-small cell lung cancer (NSCLC). There are no identified or clinically validated biomarkers to determine the efficacy of bevacizumab. In this study, we assessed the adequacy of chemokine (C-X-C motif) ligand 16 (CXCL16) as a biomarker for patients treated with bevacizumab-containing chemotherapy regimen.MethodsPatients diagnosed histologically with NSCLC were enrolled. Serial serum CXCL16 levels during treatment were measured by enzyme-linked immunosorbent assay. The relationship between serum CXCL16 levels before and after treatment, progression-free survival, and overall survival were analyzed. CXCL16 and VEGF-A expressions in lung cancer tissue were also evaluated by immunohistochemical tests.ResultsThe median serum level of CXCL16 in these patients was 3.4 ng/mL, which was significantly higher than that in age-matched healthy adults (2.2 ng/mL). Immunohistochemistry results showed that CXCL16 was predominantly localized in the tumor stroma, whereas VEGF was expressed in tumor cells. Including bevacizumab with chemotherapy led to lower CXCL16 levels post-chemotherapy, which correlated with better response rates. In addition, evaluation of differences in serum CXCL16 levels before and after the first-line chemotherapy showed that longer overall survival was achieved in patients who showed a larger decrease in serum CXCL16 levels.ConclusionsAccording to our findings, serum CXCL16 level was identified as a potential biomarker for the efficacy of therapy, including anti-VEGF.Key pointsSignificant findings of the study Patients with NSCLC whose serum CXCL16 levels decreased below 0.07 ng/mL after chemotherapy, showed longer overall survival than those without this decrease. Moreover, low CXCL16 levels corresponded to better response rates among patients with advanced NSCLC treated with bevacizumab-containing chemotherapy. What this study adds Previously there were no identifiable predictive biomarkers to determine the efficacy of bevacizumab. Data from our findings identified serum CXCL16 level as a potential biomarker for the efficacy of bevacizumab-containing chemotherapy.

Dataset Information

Clinical significance of topoisomerase-II expression in patients with advanced non-small cell lung cancer treated with amrubicin.

Publications

Clinical significance of topoisomerase-II expression in patients with advanced non-small cell lung cancer treated with amrubicin.

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