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Abstract Background For chronic pain after thoracic surgery, optimal timing of its diagnosis and effective treatment remains unresolved, although several treatment options are currently available. We examined the efficacy and safety of mirogabalin, in combination with conventional pain therapy (nonsteroidal anti-inflammatory drugs and/or acetaminophen), for treating peripheral neuropathic pain (NeP) after thoracic surgery. Methods In this multicenter, randomized, open-label, parallel-group study, patients with peripheral NeP were randomly assigned 1:1 to mirogabalin as add-on to conventional therapy or conventional treatment alone. Results Of 131 patients of consent obtained, 128 were randomized (mirogabalin add-on group, 63 patients; conventional treatment group, 65 patients). The least squares mean changes (95% confidence interval [CI]) in Visual Analogue Scale (VAS) score for pain intensity at rest from baseline to Week 8 (primary endpoint) were − 51.3 (− 54.9, − 47.7) mm in the mirogabalin add-on group and − 47.7 (− 51.2, − 44.2) mm in the conventional group (between-group difference: − 3.6 [95% CI: − 8.7, 1.5], P = 0.161). However, in patients with Self-administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) score (used for the screening of NeP) ≥ 12 at baseline, the greater the S-LANSS score at baseline, the greater the decrease in VAS score in the mirogabalin add-on group, while no such trend was observed in the conventional treatment group (post hoc analysis). This between-group difference in trends was statistically significant (interaction P value = 0.014). Chronic pain was recorded in 7.9% vs. 16.9% of patients (P = 0.171) at Week 12 in the mirogabalin add-on vs. conventional treatment groups, respectively. Regarding activities of daily living (ADL) and quality of life (QOL), changes in Pain Disability Assessment Scale score and the EQ-5D-5L index value from baseline to Week 8 showed significant improvement in the mirogabalin add-on group vs. conventional treatment group (P

Abstract Background The current standard postoperative treatment for stage II-IIIA non-small cell lung cancer (NSCLC) is a regimen of platinum doublet adjuvant chemotherapy. These regimens, which are the same as for solid NSCLC tumors, often cause severe adverse reactions in the treated patients. Therefore, an effective treatment regimen with fewer side effects is needed. Methods/design The purpose of this study is to evaluate the effectiveness and safety of S-1 monotherapy (80 mg/m2 orally administrated twice daily, at day 1–14, 16 cycles) and cisplatin with vinorelbine combination therapy (cisplatin 80 mg/m2 at day 1,vinorelbine 25 mg/m2 at day 1, 8, 4 cycles) in patients with II/IIIA stage non-small-cell lung cancer who underwent a total resection. In addition, we will also evaluate the level of treatment side effects by assessing quality of life (QOL), work productivity and activity performance. The primary endpoint is a 2-year relapse free survival (RFS) and the second primary endpoints are 2-year overall survival (OS), rate of treatment completion, safety, work productivity and activity, and quality of adjusted life years (QALY). At the same time, we aim to obtain precise information required to perform future phase 3 randomized controlled trials. The study is designed to estimate the primary endpoint with accuracy determined as the width of its 95% confidence interval to be less than 20%. Recruitment started in May 2017 and is ongoing. Discussion This study has been conceived to establish a superior regimen for completely resected NSCLC based on efficacy, safety and QOL. Trial registration Registry number: UMIN000027435 . Registered May 22, 2017.

Background: It has been shown that epidermal growth factor receptor (EGFR) mutation status is associated with 5-fluorouracil (5-FU) sensitivity in non-small-cell lung cancer (NSCLC). However, the relationship between EGFR mutation status and dihydropyrimidine dehydrogenase (DPD), a 5-FU degrading enzyme, is unknown.Methods: We elucidated the crosstalk among the EGFR signal cascade, the DPD gene (DPYD), and DPD protein expression via the transcription factor Sp1 and the effect of EGFR mutation status on the crosstalk.Results: In the PC9 (exon19 E746-A750) study, EGF treatment induced up-regulation of both Sp1 and DPD; gefitinib, an EGFR-tyrosine kinase inhibitor (EGFR-TKI), and mithramycin A, a specific Sp-1 inhibitor, suppressed them. Among EGFR-mutated (PC9, HCC827; exon19 E746-A750 and H1975; exon21 L858R, T790M, gefitinib resistant) and -non-mutated (H1437, H1299) cell lines, EGF administration increased DPYD mRNA expression only in mutated cells (p < 0.05). Accordingly, gefitinib inhibited DPD protein expression only in PC9 and HCC827 cells, and mithramycin A inhibited it in EGFR-mutated cell lines, but not in wild-type. FU treatment decreased the level of cell viability more in gefitinib-treated EGFR-TKI sensitive cell lines. Further, combination treatment of FU and mithramycin A suppressed cell viability even in a gefitinib resistant cell line.Conclusions: The EGFR signal cascade regulates DPD expression via Sp1 in EGFR mutant cells. These results might be a step towards new therapies targeting Sp1 and DPD in NSCLC with different EGFR mutant status. [ABSTRACT FROM AUTHOR]