Abstract
BackgroundAdjuvant chemotherapy after the resection of stage IB-IIIA non-small cell lung cancer (NSCLC) is now the standard of care based on large-scale phase III trials and a meta-analysis. However, chemotherapy has plateaued in terms of its efficacy, and the search for treatment prediction biomarkers is imperative for the further identification of treatable subgroups. Therefore, we investigated the significance of cyclooxygenase-2 (Cox-2) expression and the applicability of a Cox-2 inhibitor in patients who had received adjuvant chemotherapy.MethodsWe conducted a retrospective review of data from 97 patients who had received adjuvant chemotherapy. The adjuvant chemotherapy consisted of an oral tegafur agent (OT) or platinum-based chemotherapy (PB). The criteria for regimen selection were based on a discussion among the cancer board and enrollment in a clinical trial. Immunohistochemical staining (IHC) for Cox-2 was performed, and the correlation between Cox-2 expression and disease-free survival (DFS) was evaluated.ResultsIHC showed that 56 cases (57.7%) were positive for Cox-2. The rate of Cox-2 expression was similar for the PB and OT groups. Among the patients who received PB, the DFS of the patients with Cox-2 expression was significantly poorer than that of the patients without Cox-2 expression (P = 0.017), but there was no significant difference among the patients who received OT (P = 0.617). In a multivariate analysis, Cox-2 expression and lymph node metastasis were independent predictors of DFS among patients who received PB.ConclusionsCox-2 expression was a powerful predictor of DFS among patients who received PB as an adjuvant chemotherapy. Further study investigating the use of a Cox-2 inhibitor for adjuvant chemotherapy is needed.
Highlights
Adjuvant chemotherapy after the resection of stage IB-IIIA non-small cell lung cancer (NSCLC) is the standard of care based on large-scale phase III trials and a meta-analysis
We investigated the significance of Cox-2 expression among NSCLC patients who have received adjuvant chemotherapy
oral tegafur agent (OT) is widely used in Japan [19,20]. 5-Fluorouracil (5-FU)-derived agents, such as UFT and S1, are effective for patients with NSCLC who have a low expression of thymidylate synthase (TS) [21]
Summary
Adjuvant chemotherapy after the resection of stage IB-IIIA non-small cell lung cancer (NSCLC) is the standard of care based on large-scale phase III trials and a meta-analysis. We investigated the significance of cyclooxygenase-2 (Cox-2) expression and the applicability of a Cox-2 inhibitor in patients who had received adjuvant chemotherapy. The most effective treatment of early-stage non-small cell lung cancer (NSCLC) is surgical resection. Adjuvant chemotherapy after the resection of stage II-IIIA NSCLC is the standard of care based on three large-scale phase III trials and an individual patient meta-analysis [1,2,3,4]. Chemotherapy has Cyclooxygenase (Cox) is the key enzyme required for the conversion of arachidonic acid to prostaglandins (PGs). Two Cox isoforms have been identified and are referred to as constitutive Cox (Cox-1) and inducible Cox (Cox-2); Cox-2 is an inducible enzyme that is activated in response to extracellular stimuli, such as growth
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