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"Congener of FLUOROURACIL with comparable antineoplastic action. It has been suggested especially for the treatment of breast neoplasms." (MeSH 2013)

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Latest Research Publications

Web Resources: Tegafur-uracil (5 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Chen J, Wang J, Xu T
Comparison of efficacy and safety of S-1 and capecitabine in patients with metastatic colorectal carcinoma: A systematic review and meta-analysis.
Medicine (Baltimore). 2019; 98(30):e16667 [PubMed] Related Publications
BACKGROUND: This study aimed to compare the efficacy and safety of S-1 and capecitabine in patients with metastatic colorectal carcinoma (mCRC).
METHODS: Eligible prospective clinical trials were searched and available data were extracted. Odds ratio and hazard ratio of available outcomes including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were pooled for analysis.
RESULTS: A total of 6 studies including 828 patients were included. The results of pooled analysis showed no statistical difference in short-term efficacy including ORR (95% confidence interval [CI]: 0.68-1.19; P = .48) or DCR (95% CI: 0.65-1.29; P = .61), or long-term efficacy including PFS (95% CI: 0.75-1.08; P = .26) or OS (95% CI: 0.78-1.13; P = .50). Symptoms of diarrhea at any grade were more prevalent (95% CI: 1.21-2.29; P = .002) in patients treated with S-1, while hand-foot syndrome (HFS) at any grade (95% CI: 0.24-0.48; P < .0001) or high grade (95% CI: 0.09-0.48; P < .0001) was more frequent in capecitabine group. AEs including leucopenia, neutropenia, anemia, thrombocytopenia, vomiting, oral mucositis, stomatitis, elevated alanine transaminase, or peripheral neuropathy showed no statistical difference between S-1 and capecitabine group (all P > .05).
CONCLUSIONS: This meta-analysis reveals that S-1 has comparable efficacy, lower risk of HFS and higher incidence of diarrhea compared to capecitabine for treatment in patients with mCRC.

Ito T, Honma Y, Hirano H, et al.
S-1 Monotherapy After Failure of Platinum Plus 5-Fluorouracil Chemotherapy in Recurrent or Metastatic Esophageal Carcinoma.
Anticancer Res. 2019; 39(7):3931-3936 [PubMed] Related Publications
BACKGROUND/AIM: Platinum plus 5-fluorouracil (FP) is a first-line regimen of palliative chemotherapy for recurrent or metastatic esophageal squamous cell carcinoma (RM-ESCC). In this retrospective study, we evaluated the efficacy and safety of S-1 monotherapy as a salvage line treatment for RM-ESCC, focusing on the reasons for discontinuation of prior FP.
MATERIALS AND METHODS: The subjects of this study had RM-ESCC and received S-1 after failure of FP.
RESULTS: Eleven patients were enrolled. Nine patients were refractory and two were intolerant to prior FP. The median progression-free survival and overall survival time were 3.0 and 11.7 months, respectively. Overall response rate was 22.2% and disease control rate of the 11 patients was 36.4%. Median relative dose intensity of 5-FU was 100% (range=85-100%).
CONCLUSION: S-1 efficacy in RM-ESCC when given after FP was modest. Favorable OS may be attributed to good local control rather than to the efficacy of S-1 monotherapy.

Xiao C, Qian J, Zheng Y, et al.
A phase II study of biweekly oxaliplatin plus S-1 combination chemotherapy as a first-line treatment for patients with metastatic or advanced gastric cancer in China.
Medicine (Baltimore). 2019; 98(20):e15696 [PubMed] Free Access to Full Article Related Publications
Oxaliplatin plus S-1 (SOX) was a first-line regimen for advanced gastric cancer. The continuous administration of S-1 for 3 weeks can result in unacceptable gastrointestinal and hematological toxicities. Therefore, an alternative regimen (administration of S-1 for 1-week followed by 1-week rest) is warrant for improved tolerability and noninferiority efficacy. We conducted a study to evaluate the efficacy and safety of biweekly SOX as the first-line chemotherapy in patients with metastatic or advanced gastric cancer in China.Patients with metastatic or previously untreated advanced gastric cancer were enrolled. Oxaliplatin was administered intravenously at a dose of 85 mg/m on day 1, while S-1 was administered orally in doses of 80, 100, or 120 mg/day depending on different body surface areas of <1.25 m, 1.25-1.5 m, or >1.5 m respectively; the total dose of S-1 was administered twice daily on days 1-7 followed by a 7-day rest. This schedule was repeated every 2 weeks until disease progressed or intolerable toxicity occurred.Forty-six patients (M/F = 33/13) received biweekly oxaliplatin and S-1 as first-line chemotherapy. A total of 257 treatment cycles were administered and the median number of cycles administered was 6. Thirty-six patients (78.3%) received second-line chemotherapy. The median progression free survival and median overall survival was 4.4 months (95% CI, 3.37-5.36 months) and 10.3 months (95% CI, 8.88-11.3 months), respectively. The 1-year and 2-year survival rate was 41% and 13%. The objective response rate was 30.43%, and the disease control rate was 76.08%. The observed adverse events of Grade 3/4 included were leukocytopenia (13.04%); anemia (13.04%); neutropenia (15.22%); neurological toxicity (2.17%); diarrhea (2.17%).The biweekly SOX regimen as first-line treatment was active and well tolerated in Chinese patients with metastatic or advanced gastric cancer.

Kaira K, Imai H, Souma R, et al.
An Exploratory Randomized Phase II Trial Comparing CDDP Plus S-1 With Bevacizumab and CDDP Plus Pemetrexed With Bevacizumab Against Patients With Advanced Non-squamous Non-small Cell Lung Cancer.
Anticancer Res. 2019; 39(5):2483-2491 [PubMed] Related Publications
BACKGROUND/AIM: It remains unclear which chemotherapeutic regimens are better for the addition of bevacizumab. We conducted an exploratory randomized phase II trial comparing first-line S-1 plus cisplatin with bevacizumab and pemetrexed plus cisplatin with bevacizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC).
PATIENTS AND METHODS: Chemotherapy-naïve patients received S-1 (80 mg/m
RESULTS: Forty-eight patients were enrolled in this study, and eligible patients were randomly assigned at 1:1 ratio to receive SCB (n=24) or PCB (n=24). The median number of chemotherapy and maintenance therapy for SCB and PCB was 4 (range, 1-6 cycles) and 4 (range, 2-6 cycles), and 5 (range, 0-39 cycles) and 5 (range, 0-28 cycles), respectively. The overall response rate (ORR) for PCB and SCB were 54.2% and 83.3%, respectively (p=0.06). The median progression-free survival (PFS) and overall survival (OS) for PCB and SCB were 406 and 351 days, (p=0.96), and 678 and 1190 days, respectively (p=0.23). The mild adverse events were observed in both regimens. TS expression was more predictive of the chemotherapeutic response in SCB compared to PCB, but not for PFS.
CONCLUSION: The combination regimen of SCB was identified as having a similar activity and tolerability to that of PCB in patients with advanced non-squamous NSCLC.

Morita Y, Sakaguchi T, Kitajima R, et al.
Body weight loss after surgery affects the continuity of adjuvant chemotherapy for pancreatic cancer.
BMC Cancer. 2019; 19(1):416 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Postoperative chemotherapy is beneficial for many pancreatic cancer patients. However, some patients require dose reduction or the discontinuation of adjuvant chemotherapy because of adverse treatment-related effects. In this study, we aimed to evaluate two main outcomes. First, we evaluated the clinicopathological factors affecting patient disease-free survival (DFS) and overall survival (OS) following upfront surgery. Second, we evaluated the factors that influence the continuity of adjuvant chemotherapy.
METHODS: Fifty-four patients with resected pancreatic cancer were enrolled. First, we evaluated the clinicopathological factors affecting postoperative survival using the Kaplan-Meier method and Cox regression method. Next, factors affecting the continuity of adjuvant chemotherapy were analyzed using multiple logistic regression analysis.
RESULTS: Univariate and multivariate analyses revealed that positive LN metastasis (HR (95% CI) 6.329 (2.381-16.95); p < 0.001) and relative dose intensity (RDI) < 80% for adjuvant chemotherapy (HR (95% CI) 5.154 (1.761-15.15); p = 0.003) were independent predictive factors for DFS. Regarding OS, extended dissection of the nerve plexus around the superior mesenteric artery (SMA) (HR (95% CI) 4.504 (1.721-11.76); p = 0.002), positive microscopic surgical margin (HR (95% CI) 5.565 (1.724-17.96); p = 0.004), and adjuvant chemotherapy of RDI < 80% (HR (95% CI) 3.534 (1.135-2.667); p = 0.029) were also independent predictive factors. Moreover, the level of RDI significantly correlated with DFS and OS. Multiple logistic regression analysis revealed that low RDI was significantly associated with postoperative body weight loss (BWL) ≥ 10%.
CONCLUSIONS: The following factors were significantly associated with poor survival: extended dissection of the nerve plexus around the SMA, lymph node metastasis, residual tumor, and RDI of the adjuvant chemotherapy. Patient's prognosis with adjuvant chemotherapy of RDI < 80% was worse. BWL ≥10% was the most important factor affecting the continuity of adjuvant chemotherapy. Perioperative nutritional intervention is necessary for patients who receive adjuvant chemotherapy for advanced pancreatic cancer.

Yasui H, Kawakami T, Kashiwagi H, et al.
Pharmacokinetics of S-1 monotherapy in plasma and in tears for gastric cancer patients.
Int J Clin Oncol. 2019; 24(6):660-665 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: S-1 is an oral anticancer drug composed of tegafur (FT), which is a prodrug of 5-FU, 5-chloro-2,4-dihydroxypyridine (CDHP), and potassium oxonate. Recently, some studies have been reported on watering eyes caused by S-1. However, the mechanism of watering eyes caused by S-1 is still unclear. The aim of this study was to investigate the correlation between tears and plasma concentrations of FT, 5-FU, and CDHP, which are components and active modulator of S-1.
METHODS: We prospectively investigated the pharmacokinetics (PK) of FT, 5-FU, and CDHP in plasma and in tears of gastric cancer patients who were treated with S-1 monotherapy at the dose of 80 mg/m
RESULTS: Total of eight patients were enrolled. All the FT, 5-FU and CDHP were detected both in plasma and in tears, and their PK parameters were measured. There was a positive correlation between the concentrations of FT, 5-FU and CDHP in the plasma and those in the tears on day 1 and day 14 (correlation coefficients r, right eye/left eye: r = 0.882/0.878, 0.877/0.890, and 0.885/0.878, respectively).
CONCLUSION: There was a positive correlation between the concentrations of FT, 5-FU and CDHP in the plasma and those in the tears. The result is expected to facilitate the further investigation into the causes of watering eyes and the establishment of the effective methods for the prevention and the treatment.

Yoshida Y, Beppu T, Kinoshita K, et al.
Five-year Recurrence-free Survival After Surgery Followed by Oral Chemotherapy for Gastric Cancer With Portal Vein Tumor Thrombosis.
Anticancer Res. 2019; 39(4):2233-2238 [PubMed] Related Publications
Gastric cancer with portal vein tumor thrombosis (GC-PVTT) is a rare condition with a very poor prognosis. A 64-year-old man with GC-PVTT was admitted to our hospital. His carcinoembryonic antigen level was slightly elevated (17.4 ng/ml). Upper gastrointestinal endoscopy showed a type-2 gastric lesion (45 mm × 40 mm) in the gastric antrum. The PVTT originated from the main gastric tumor and continued to the superior mesenteric vein. Fluorodeoxyglucose-positron emission tomography showed high uptake both by the main tumor and PVTT. A distal gastrectomy with D2 lymphadenectomy was performed with simultaneous removal of the PVTT. Pathological examination showed a poorly differentiated adenocarcinoma with neuroendocrine differentiation. Adjuvant chemotherapy with S-1 was administered for 1 year. The patient survived for >5 years with no recurrence. Surgical gastrectomy and complete removal of the PVTT followed by S-1 chemotherapy could be a treatment option that offers improved long-term survival for patients with GC-PVTT.

Liu JB, Jian T, Yue C, et al.
Chemo-resistant Gastric Cancer Associated Gene Expression Signature: Bioinformatics Analysis Based on Gene Expression Omnibus.
Anticancer Res. 2019; 39(4):1689-1698 [PubMed] Related Publications
BACKGROUND/AIM: This study aimed to identify biomarkers for predicting the prognosis of advanced gastric cancer patients who received docetaxel, cisplatin, and S-1 (DCS).
MATERIALS AND METHODS: Gene expression profiles were obtained from the Gene Expression Omnibus database (GSE31811). Gene-Ontology-enrichment and KEGG-pathway analysis were used for evaluating the biological functions of differentially-expressed genes. Protein-protein interaction (PPI) network and Kaplan-Meier survival analyses were employed to assess the prognostic values of hub genes.
RESULTS: A total of 1,486 differentially expressed genes (DEGs) were identified, including 13 up-regulated and 1,473 down-regulated genes. KEGG pathways such as metabolic pathways, cell adhesion molecules (CAMs), PI3K-Akt signaling pathway and pathways in cancer were significantly represented. In the PPI network, the top ten hub genes ranked by degree were GNG7, PLCB1, CALML5, FGFR4, GRB2, JAK3, ADCY7, ADCY9, GNAS and KDR. Five DEGs, including ANTXR1, EFNA5, GAMT, E2F2 and NRCAM, were associated with relapse-free survival and overall survival.
CONCLUSION: ANTXR1, EFNA5, GAMT, E2F2 and NRCAM are potential biomarkers and therapeutic targets for DCS treatment in GC.

Han L, Wei ZX, Lv YF, Jiang AY
Efficacy of carboplatin plus S-1 for the treatment of non-small cell lung cancer: A protocol for a systematic review of randomized controlled trial.
Medicine (Baltimore). 2019; 98(14):e15099 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common lung cancer. Numerous clinical studies have reported that the combination of carboplatin and S-1 (CS) can be used to treat NSCLC effectively. However, no systematic review has been conducted to assess its efficacy and safety for NSCLC. This systematic review aims to evaluate the efficacy and safety of CS for treatment of patients with NSCLC.
METHODS: This study will retrieve the following electronic databases from inception to the February 1, 2019: Cochrane Library, EMBASE, MEDILINE, CINAHL, AMED, and 4 Chinese databases without any language limitations. This systematic review will include randomized controlled trials (RCTs) and case-control studies for assessing the efficacy and safety of CS for the treatment of NSCLC. Cochrane risk of bias will be used as methodological quality assessment for each qualified study. The RevMan V.5.3 software will be utilized to synthesize the data and conduct the meta-analysis if it is allowed. The data will be pooled by using the random-effects model or fixed-effects model.
RESULTS: The primary outcome is overall response rate. The secondary outcomes are overall survival, progression-free survival, the disease control rate, and any adverse events.
CONCLUSION: It will provide latest evidence to determine the efficacy and safety of CS for treatment of patients with NSCLC.
ETHICS AND DISSEMINATION: No research ethic approval is needed in this study because this study will not analyze individual patient data. The results are expected to disseminate through peer-reviewed journals.

Liang D, Yang B
Short-term efficacy of oral low-dose Tegafur chemotherapy after transarterial chemoembolization in primary hepatic carcinoma.
J BUON. 2019 Jan-Feb; 24(1):171-177 [PubMed] Related Publications
PURPOSE: To observe the short-term efficacy of oral low-dose Tegafur chemotherapy after transarterial chemoembolization (TACE) in primary hepatic carcinoma (PHC).
METHODS: 120 PHC patients undergoing TACE treatment for the first were randomly divided into the Tegafur group and the TACE group. Patients in TACE group received TACE only, whereas those in the Tegafur group received TACE and postoperative oral low-dose Tegafur chemotherapy. All patients were followed up for 4 to 20 months. Clinical efficacy, liver function changes, progression-free survival (PFS), and adverse reactions were compared between the two groups.
RESULTS: The disease control rate (DCR) and clinical benefit rate (CBR) of the Tegafur group were significantly higher than those of TACE group (p<0.05). Moreover, higher PFS was found in the Tegafur group than that of the TACE group after 18 months of follow-up (p<0.05). Before treatment, serum levels of ALT, AST, TBIL and DBIL in the two groups were not statistically significant (p>0.05). After treatment, the above-mentioned indicators were remarkably increased in both groups. In particular, the indicators were lower in the Tegafur group than those of the TACE group (p<0.05).
CONCLUSIONS: TACE combined with low-dose Tegafur for treating PHC can slow down the tumor progression and prolong the PFS. This approach is safe and effective.

Huang J, Xu B, Liu Y, et al.
Irinotecan plus S-1 versus S-1 in patients with previously treated recurrent or metastatic esophageal cancer (ESWN 01): a prospective randomized, multicenter, open-labeled phase 3 trial.
Cancer Commun (Lond). 2019; 39(1):16 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The benefit of systemic treatments in esophageal squamous cell carcinoma (ESCC) which has progressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been established. We aimed to compare the efficacy of irinotecan plus S-1 with S-1 monotherapy in recurrent or metastatic ESCC patients who had resistance to platinum- or taxane-based chemotherapy.
METHODS: We conducted a prospective randomized, multicenter, open-label, phase 3 trial in 15 centers across China. Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC, and were randomly assigned (ratio, 1:1) to receive either irinotecan plus S-1 (intravenous infusion of irinotecan [160 mg/m
RESULTS: Between December 23, 2014 and July 25, 2016, we screened 148 patients and randomly assigned 123 patients to receive either irinotecan plus S-1 regimen (n = 61) or S-1 monotherapy (n = 62). After a median follow-up of 29.2 months (95% confidence interval [CI] 17.5-40.9 months), the median PFS was significantly longer in the irinotecan plus S-1 group than in the S-1 monotherapy group (3.8 months [95% CI 2.9-4.3 months] vs. 1.7 months [95% CI 1.4-2.7 months], hazard ratio = 0.58, 95% CI 0.38-0.86, P = 0.006). The objective response rates were 24.6% in the irinotecan plus S-1 group and 9.7% in the S-1 monotherapy group (P = 0.002). The patients in the irinotecan plus S-1 group presented with increased rates of grade 3-4 leukopenia (16.4% vs. 0%), neutropenia (14.8% vs. 1.6%), and nausea (4.9% vs. 0%). No significant difference in grade 3-4 diarrhea and no treatment-related deaths were observed in both groups.
CONCLUSIONS: The combination of irinotecan with S-1 was similarly tolerable but significantly prolonged PFS compared to S-1 monotherapy as a second- or third-line treatment in patients with recurrent or metastatic ESCC. Clinical Trial Registration NCT02319187. Registered on December 9, 2014.

Kojima Y, Yoshie R, Kawamoto H, et al.
Trastuzumab Emtansine (T-DM1) Plus S-1 in Patients with Trastuzumab-Pretreated HER2-Positive Advanced or Metastatic Breast Cancer: A Phase Ib Study.
Oncology. 2019; 96(6):309-317 [PubMed] Related Publications
BACKGROUND: In treating human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, the efficacy of capecitabine combined with HER2-directed agents such as trastuzumab and lapatinib is supported by some evidence. The combination of T-DM1 and S-1, another oral 5-FU, may be a safe alternative treatment for metastatic breast cancer.
OBJECTIVES: The optimal dose of S-1 was evaluated in combination with T-DM1 for patients with HER2-positive advanced or metastatic breast cancer. The safety and clinical response of this combination treatment were also assessed.
METHODS: This 3 + 3 dose-escalation study of S-1 given for the first 2 of 3 weeks, in combination with T-DM1 (3.6 mg/kg given every 3 weeks) to patients with trastuzumab-pretreated HER2-positive advanced or metastatic breast cancer was designed to evaluate the dose-limiting toxicity (DLT) occurrence in the first cycle. We also evaluated the safety and clinical activity of this combination treatment in multiple cycles. Two different dose levels of S-1 (65 and 80 mg/m2/day) were planned, although the capecitabine arm was abandoned because of slow recruitment.
RESULTS: Twelve out of the 13 patients enrolled were evaluable for DLT. One DLT (grade ≥3 non-hematological adverse events) occurred at dose level 0, leading to the expansion of this cohort to 6 patients, with an additional DLT (≥7 days discontinuation of medication), while no DLT occurred at dose level 1. As a result, the maximum tolerable dose of S-1 was determined to be 80 mg/m2/day for 14 days with T-DM1 3.6 mg/kg, repeated every 3 weeks. Two patients had grade 3 thrombocytopenia at dose level 0, and 1 patient at dose level 1.
CONCLUSIONS: S-1 can be safely combined with the clinically relevant dose of T-DM1 in patients with HER2-positive advanced or metastatic breast cancer. Further evaluation with a larger sample size is required for efficacy assessment.

Sugawara S, Nakagawa K, Yamamoto N, et al.
Japanese subgroup analysis of a phase III study of S-1 versus docetaxel in non-small cell lung cancer patients after platinum-based treatment: EAST-LC.
Int J Clin Oncol. 2019; 24(5):485-493 [PubMed] Free Access to Full Article Related Publications
INTRODUCTION: The East Asia S-1 Trial in Lung Cancer (EAST-LC) was a randomized phase III study conducted in East Asia that demonstrated the non-inferiority of S-1 to docetaxel in previously treated patients with advanced non-small cell lung cancer (NSCLC). Here, we reported the results of the Japanese subgroup treated with docetaxel 60 mg/m
PATIENTS AND METHODS: Patients were randomized 1:1 to receive either S-1 or docetaxel. The primary endpoint was overall survival (OS); the secondary endpoints included progression-free survival (PFS), response rate (RR), quality of life (QOL), and safety.
RESULTS: Patient characteristics in the Japanese subgroup (n = 724) were similar to those in the overall EAST-LC population. Median OS was 13.4 months in the S-1 group and 12.6 months in the docetaxel group. In pemetrexed-pretreated patients, OS with S-1 was similar to that with docetaxel. Median PFS was 2.9 and 3.0 months in the S-1 and docetaxel groups, respectively. RR was 9.4% and 10.3% in the S-1 and docetaxel groups, respectively. The QOL of patients treated with S-1 was better compared with that of patients treated with docetaxel. Decreased appetite and diarrhea were more common in the S-1 group, whereas the frequency of neutropenia and febrile neutropenia was markedly higher in the docetaxel group.
CONCLUSIONS: This Japanese subgroup analysis showed that S-1 had similar efficacy to docetaxel in patients with previously treated advanced NSCLC. These results are similar to those of the overall EAST-LC population.

Sun S, Yu H, Wang H, et al.
Phase II Study of S-1 plus Cisplatin as First-Line Therapy in Patients with Metastatic Esophageal Carcinoma.
Oncol Res Treat. 2019; 42(3):115-122 [PubMed] Related Publications
BACKGROUND: Patients with metastatic esophageal squamous cell cancer (ESCC) need safer and more efficacious treatments. The aim of this phase II study was to investigate the efficacy and safety of S-1 plus cisplatin as first-line therapy in metastatic ESCC.
PATIENTS AND METHODS: 50 patients with metastatic ESCC who had not received prior systemic chemotherapy for metastatic disease were enrolled. Patients received S-1 at 40 mg/m2 divided into 2 daily doses for 14 days and cisplatin at 75 mg/m2 on day 1 or 25 mg/m2 on days 1-3 intravenously, repeated every 21 days with a maximum of 6 cycles.
RESULTS: 47 patients were assessable for response and 18 patients achieved a partial response, giving an overall response rate of 38.3%. Among those who had objective responses, a large percentage (72.2%) quickly showed remarkable tumor shrinkage during the first 2 cycles. 18 (38.3%) patients had stable disease. The median progression-free survival was 5.6 months, and the median overall survival was 12.0 months. Toxicity was mild to moderate and generally tolerable.
CONCLUSION: The combination of S-1 plus cisplatin was a well-tolerated and convenient chemotherapy regimen with promising efficacy.

Tanioka H, Honda M, Tanaka C, et al.
Biweekly S-1 plus oxaliplatin (SOX) reintroduction in previously treated metastatic colorectal cancer patients (ORION 2 study): a phase II study to evaluate the efficacy and safety.
Int J Clin Oncol. 2019; 24(7):836-841 [PubMed] Related Publications
BACKGROUND: The reintroduction of oxaliplatin as a third-or-later-line regimen has been a promising option for patients with metastatic colorectal cancer (mCRC) who previously received chemotherapy including oxaliplatin. In this single-arm phase II study, we evaluated the efficacy of biweekly SOX, which is the combination of oxaliplatin reintroduction and S-1, as a third-or-later-line treatment.
METHODS: Patients with mCRC who had previously received prior chemotherapy including oxaliplatin and irinotecan and were planned to receive the reintroduction of oxaliplatin were enrolled. Oxaliplatin (85 mg/m
RESULTS: A total of 41 patients from 12 institutes were enrolled. The median PFS and OS survival were 3.3 months (95% confidence interval [CI] 2.7-4.2) and 10.1 months (8.3-14.6), and response rate and disease control rate were 10.0% and 65.0%, respectively. Grade 3 AEs included thrombocytopenia (5.0%), anorexia (5.0%), pneumonia (5.0%) and fatigue (5.0%). There were no cases of grade 4 AEs or treatment-related death.
CONCLUSION: Biweekly SOX regimen with reintroduction of oxaliplatin could be exploitable as the third- and/or later-line treatments for patients with mCRC.

Yokoi T, Minami S, Shiroyama T, et al.
A Phase II Study of Tailored-dose S-1 Plus Carboplatin Followed by Maintenance S-1 for Advanced Squamous Cell Lung Cancer: OSAKA-LCSG 1102.
Intern Med. 2019; 58(10):1405-1410 [PubMed] Free Access to Full Article Related Publications
Objective A subset analysis of the LETS study suggested that S-1 plus carboplatin was more beneficial than paclitaxel plus carboplatin in terms of the overall survival (OS) in squamous cell lung cancer. However, the benefit of maintenance therapy for squamous cell non-small cell lung cancer (NSCLC) patients is still unknown. We herein report a phase II study to evaluate the efficacy and safety of a tailored dose of S-1 plus carboplatin followed by maintenance S-1 in chemotherapy-naive advanced squamous cell NSCLC. Methods Patients received carboplatin on day 1 plus S-1 on days 1 to 14 every 21 days. The dose of S-1 was determined by the body surface area and creatinine clearance. After four cycles of induction, non-progressive patients continued to receive S-1 until disease progression or unacceptable toxicity occurred. The primary endpoint was an objective response rate (RR) with a threshold value of 15%. The secondary endpoints were the progression-free survival (PFS) and OS from enrollment, the PFS in the maintenance phase, and safety. Results In the 33 patients analyzed, the rate of patients who met the primary endpoint was 30.3% (95% confidence interval: 15.6-48.7%), and the disease control rate was 75.8%. The median PFS and OS were 3.5 and 11.3 months, respectively. Ten patients received maintenance S-1, and the median PFS from the beginning of induction treatment was 5.3 months. Grade 3/4 toxicities with a frequency of more than 5% were all controllable. Conclusion Tailored-dose S-1 plus carboplatin followed by maintenance S-1 is an effective and feasible treatment for advanced squamous cell NSCLC.

Endo S, Kurokawa Y, Gamoh M, et al.
Trastuzumab With S-1 Plus Cisplatin in HER2-positive Advanced Gastric Cancer Without Measurable Lesions: OGSG 1202.
Anticancer Res. 2019; 39(2):1059-1065 [PubMed] Related Publications
BACKGROUND/AIM: Trastuzumab with S-1 plus cisplatin was proved to be effective for human epidermal growth factor receptor type 2 (HER2)-positive advanced gastric cancer with measurable lesions. However, the efficacy and safety of this regimen in the absence of measurable lesions are unknown.
PATIENTS AND METHODS: Patients with HER2-positive gastric cancer without measurable lesions received cisplatin plus trastuzumab intravenously on day 1 and oral S-1 on days 1-14 of a 21-day cycle. The primary end-point was overall survival, and 40 patients were planned to be enrolled.
RESULTS: Fifteen patients were enrolled. The median overall survival was 14.4 months. The 1- and 3-year overall survival rates were 66.7 % and 26.7 %, respectively. Major grade 3-4 adverse events included neutropenia (47%), anemia (40%), diarrhea (20%), nausea (20%), and anorexia (20%).
CONCLUSION: Trastuzumab with S-1 plus cisplatin might be effective and tolerable for HER2-positive advanced gastric cancer without measurable lesions.

Motoi F, Kosuge T, Ueno H, et al.
Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP05).
Jpn J Clin Oncol. 2019; 49(2):190-194 [PubMed] Related Publications
A randomized, controlled trial has begun to compare neoadjuvant chemotherapy using gemcitabine and S-1 with upfront surgery for patients planned resection of pancreatic cancer. Patients were enrolled after the diagnosis of resectable or borderline resectable by portal vein involvement pancreatic cancer with histological confirmation. They were randomly assigned to either neoadjuvant chemotherapy or upfront surgery. Adjuvant chemotherapy using S-1 was administered for 6 months to patients with curative resection who fully recovered within 10 weeks after surgery in both arms. The primary endpoint is overall survival; secondary endpoints include adverse events, resection rate, recurrence-free survival, residual tumor status, nodal metastases and tumor marker kinetics. The target sample size was required to be at least 163 (alpha-error 0.05; power 0.8) in both arms. A total of 360 patients were required after considering ineligible cases. This trial began in January 2013 and was registered with the UMIN Clinical Trials Registry (UMIN000009634).

Mori M, Shuto K, Kosugi C, et al.
An increase in the neutrophil-to-lymphocyte ratio during adjuvant chemotherapy indicates a poor prognosis in patients with stage II or III gastric cancer.
BMC Cancer. 2018; 18(1):1261 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) are associated with poor prognoses in patients with gastric cancer; however, few studies have focused on the dynamic changes in these ratios during the treatment of patients with gastric cancer. Here, we assessed the clinical utility of changes in these ratios as prognostic indicators in patients with stage II or III gastric cancer who received adjuvant chemotherapy.
METHODS: We retrospectively reviewed 100 patients who received S-1 adjuvant chemotherapy at ≥70% of the relative dose intensity, and their NLRs and PLRs were evaluated at different times: prior to gastrectomy and upon commencement and termination of adjuvant chemotherapy. To assure the clinical utility of the changes in NLR and PLR as prognostic indicators, other clinical factors were assessed as well.
RESULTS: Disease recurred in 35 patients as follows: lymph node metastasis (17 patients, 17.0%), peritoneal metastasis (12 patients, 12.0%), and hematogenous metastasis (6 patients, 6.0%); 24 patients died. An increase in the NLR during adjuvant chemotherapy with S-1 was identified as an independent indicator associated with overall survival (hazard ratio [HR] 6.736, 95% confidence interval [CI] 2.420-18.748; P < 0.001), and relapse-free survival (HR 5.309, 95% CI 2.585-10.901; P < 0.001).
CONCLUSION: An increase in the NLR during S-1 adjuvant chemotherapy may be a useful prognostic indicator in patients with stage II or III gastric cancer.

Yang L, Wang X, Wang B, et al.
The clinical outcomes of S-1 plus cisplatin for patients with advanced gastric cancer: A meta-analysis and systematic review.
Medicine (Baltimore). 2018; 97(49):e12789 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: To evaluate the clinical outcomes of S-1 plus cisplatin (SC) for the treatment of patients with advanced gastric cancer (AGC).
METHODS: A systematic literature search was conducted by searching PubMed, the Cochrane Library, Embase, China Biology Medicine disc (CBMdisc), China National Knowledge Infrastructure (CNKI), and WanFang Database, for all year up to January 2017. Pooled analyses of overall survival (OS), progress-free survival rates, and adverse events were performed.
RESULTS: A total of 8 random controlled trails (RCTs) consisting of 2699 patients with AGC were selected and included in this meta-analysis. The results of our meta-analysis showed that AGC patients who treated with SC regimen receive a similar OS (HR = 1.01, 95%CI: 0.86-1.18, P = .928), PFS (HR = 0.89, 95%CI: 0.72-1.09, P = .263), and overall response rate (HR = 0.88, 95%CI: 0.70-1.11, P = .283). However, SC regimen may increase the risk of 1 to 2 grade (OR = 1.128, 95%CI: 1.075-1.184, P = .000) and 3 to 4 grade (OR = 1.24, 95%CI: 1.01-1.52, P = .039) adverse events.
CONCLUSION: SC chemotherapy showed no difference in survival compared with 5-FU- and S-1-based other therapy, but has a higher rate of adverse events compared with other chemotherapy regimens.

Yang H, Sui Y, Guo X, et al.
Endostar continuous intravenous infusion combined with S-1 and oxaliplatin chemotherapy could be effective in treating liver metastasis from gastric cancer.
J Cancer Res Ther. 2018; 14(Supplement):S1148-S1151 [PubMed] Related Publications
Objective: Endostar is a new vascular epithelial inhibitor, which is reported to be effective in treating liver metastasis from gastric cancer. However, the optimal therapeutic regimen of Endostar remains unclear. Thus, our study aimed to examine the efficacy and safety of Endostar continuous intravenous infusion combined with S-1 and oxaliplatin (SOX) chemotherapy in treating such patients.
Patients and Methods: A total of sixty patients with liver metastasis from gastric cancer admitted in our department were enrolled. The experimental group (n = 30) was treated with Endostar continuous intravenous infusion combined with SOX regimen chemotherapy, and the control group (n = 30) received SOX regimen chemotherapy alone. All patients received at least two cycles of treatment. The objective effective rate (ORR), disease control rate (DCR), progression-free survival (PFS), and adverse reactions were recorded and compared.
Results: The ORR of the experimental group and control group was 63.3% and 43.3% (P = 0.046), respectively. The DCR of the experimental group and the control group was 86.7% and 73.3% (P = 0.034). The median PFS in the experimental group was longer than that in the control group (15.3 months vs. 12 months). There was no significant difference in the incidence of common adverse reactions such as gastrointestinal reaction, bone marrow suppression, and cardiac toxicity between the two groups. No death was observed in the study period.
Conclusion: Continuous infusion of Endostar combined with SOX chemotherapy could be recommended for the treatment of liver metastasis from gastric cancer due to its high effective rate, and Endostar did not increase the incidence of adverse reactions.

Cui S, Zhao Q, Ye M, et al.
Clinical efficacy and safety of S-1 monotherapy in the treatment of advanced breast cancer in elderly patients.
Pak J Pharm Sci. 2018; 31(5(Special)):2299-2302 [PubMed] Related Publications
To observe and analyze the therapeutic efficacy of S-1 monotherapy in the treatment of advanced breast cancer in elderly patients. A total of 180 elderly patients diagnosed as advanced breast cancer and treated at our hospital were enrolled. All patients were randomized into study group and control group, with 90 patients in each group. Of those, capecitabine monotherapy was administered in control group, while S-1 monotherapy was applied in study group. Clinical efficacy and safety of both groups were compared. By comparing recent therapeutic effects, results showed that the overall treatment efficacy was 51.11% in study group, while the value was 35.56% in control group, suggesting a higher therapeutic efficacy in study group (P<0.05). Also, the incidence of side effects was significantly lower in study group compared with control group (P<0.05). Moreover, quality of life was better preserved in study group (P<0.05). S-1 monotherapy was relatively effective and safe in the treatment of advanced breast cancer in elderly patients.

Liu Y, Zhou C, Zhang K, et al.
The combination of apatinib and S-1 for the treatment of advanced gastric cancer in China: A meta-analysis of randomized controlled trials.
Medicine (Baltimore). 2018; 97(47):e13259 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Apatinib-targeted therapy is considered a promising treatment option for malignancies. This study systematically evaluated the efficacy and safety of the combination of apatinib and S-1 for the treatment of patients with advanced gastric cancer (GC).
METHODS: Clinical trials were searched from the PubMed, Cochrane Library, Embase, CNKI, and Wanfang databases. Outcome measures including therapeutic efficacy, quality of life (QoL), and adverse events were extracted and evaluated.
RESULTS: Data from 8 trials including 393 patients with advanced GC were included. The results indicated that, compared with S-1 alone, the combination of apatinib with S-1 significantly improved patient partial response rate (odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.21-3.02, P = .005), overall response rate (ORR, OR = 2.40, 95% CI = 1.51-3.82, P = .0002), and disease control rate (DCR, OR = 2.78, 95% CI = 1.51-5.10, P = .0010), whereas the rates of complete response (CR, OR = 2.38, 95% CI = 0.93-6.12, P = .07) and stable disease (SD, OR = 0.99, 95% CI = 0.64-1.54, P = .97) and QoL (OR = 1.22, 95% CI = 0.51-2.92, P = .66) did not differ significantly. Moreover, the group receiving the combined therapy had higher rates of hand-foot syndrome (OR = 2.23, 95% CI = 1.19-4.17, P = .01), hypertension (OR = 8.85, 95% CI = 4.07-19.26, P < .00001), albuminuria (OR = 11.25, 95% CI = 3.32-38.06, P = .0001), and hemoglobin reduction (OR = 3.19, 95% CI = 1.32-7.67, P = .010), whereas analysis of other adverse events did not show significant differences (P > .05).
CONCLUSION: The combination of apatinib and S-1 is more effective for GC treatment than S-1 alone. However, this combined treatment could lead to increased hand-foot syndrome, hypertension, albuminuria, and hemoglobin reduction. Therefore, the benefits and risks should be considered before treatment.

Ishikawa T, Kawashima H, Ohno E, et al.
Randomized Phase II Study of Consecutive-Day versus Alternate-Day Treatment with S-1 as Second-Line Chemotherapy in Advanced Pancreatic Cancer.
Oncology. 2019; 96(1):1-7 [PubMed] Related Publications
OBJECTIVE: To evaluate the efficacy and safety of alternate-day administration of S-1 as second-line chemotherapy for unresectable pancreatic cancer in a multicenter, randomized, phase II study.
METHODS: Patients with histologically proven, unresectable pancreatic cancer treated with chemotherapy not including S-1 as first-line therapy were randomly assigned to receive either daily or alternate-day treatment with S-1. The primary end point was overall survival (OS), and the secondary end points were progression-free survival (PFS), time to treatment failure (TTF), response rate, and adverse events.
RESULTS: A total of 77 patients were enrolled, of which 75 were included in the final analysis. The median OS was 4.5 months in the daily group and 4.4 months in the alternate-day group (HR 1.178; 95% CI 0.741-1.875), with no significance in PFS and TTF. The response rate was 2.8% in the daily group and 0% in the alternate-day group. Grade 3 or higher adverse events occurred with significantly higher incidence in the daily group (47.2 vs. 25.6%, p = 0.044).
CONCLUSION: As a second-line chemotherapy for unresectable pancreatic cancer, although the efficacy in both groups was comparable and we can expect fewer toxicities with alternate-day administration of S-1, the noninferiority of alternate-day treatment to daily treatment with S-1 was not verified.

Zhu H, Yi C, Zhao Y, Gou H
Gemcitabine plus S-1 for metastatic pancreatic cancer.
Medicine (Baltimore). 2018; 97(41):e12836 [PubMed] Free Access to Full Article Related Publications
To investigate the treatment effects of gemcitabine plus S-1 (GS) for metastatic pancreatic cancer in our institution.Data from 41 patients with metastatic pancreatic cancer treated with GS regimen in West China Hospital, Sichuan University were reviewed. The therapeutic efficacy and toxicity were evaluated. The influencing factors of progression-free survival (PFS) and overall survival (OS) were also explored.At the last follow-up, all patients had died. The objective response rate was 22.0% (9/41) and the disease control rate was 65.9% (27/41). The median PFS and OS times were 5.1 (range, 1.5-21) and 10.6 months (range, 1.5-40), respectively. The 0.5-, 1-, and 2-year OS rates were 65.9%, 41.5%, and 9.8%, respectively. In multivariate analysis, body mass index and carbohydrate antigen 19-9 change were the significant influencing factors of PFS, compared to tumor site and chemotherapy cycles for OS. The adverse effects were moderate and tolerable.The effects of GS for metastatic pancreatic cancer in our institution were good. The adverse effects were moderate and tolerable. However, further investigation in future prospective clinical studies is warranted.

He MM, Wang F, Jin Y, et al.
Phase II clinical trial of S-1 plus nanoparticle albumin-bound paclitaxel in untreated patients with metastatic gastric cancer.
Cancer Sci. 2018; 109(11):3575-3582 [PubMed] Free Access to Full Article Related Publications
The present study is the first phase II clinical trial aimed to evaluate the efficacy and safety of S-1 plus nanoparticle albumin-bound paclitaxel (Nab-PTX) as first-line chemotherapy for advanced gastric cancer (AGC). Previously untreated patients with metastatic gastric adenocarcinoma received S-1 in oral doses of 40 mg (BSA <1.25 m

Kimura K, Yamano T, Igeta M, et al.
UGT1A1 polymorphisms in rectal cancer associated with the efficacy and toxicity of preoperative chemoradiotherapy using irinotecan.
Cancer Sci. 2018; 109(12):3934-3942 [PubMed] Free Access to Full Article Related Publications
The purpose of the present study was to assess the efficacy and toxicity of preoperative chemoradiotherapy using irinotecan against locally advanced lower rectal cancer according to UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms. Between 2009 and 2016, 46 patients with resectable rectal cancer (T3-T4, N0-N2, M0) received preoperative chemoradiotherapy consisting of 80 mg/m

Sasaki T, Seto T, Yamanaka T, et al.
A randomised phase II trial of S-1 plus cisplatin versus vinorelbine plus cisplatin with concurrent thoracic radiotherapy for unresectable, locally advanced non-small cell lung cancer: WJOG5008L.
Br J Cancer. 2018; 119(6):675-682 [PubMed] Related Publications
BACKGROUND: Cisplatin-based chemoradiotherapy is the standard treatment for unresectable, locally advanced non-small-cell lung cancer (NSCLC). This trial evaluated two experimental regimens that combine chemotherapy with concurrent radiotherapy.
METHODS: Eligible patients with unresectable stage III NSCLC were randomised to either the SP arm (S-1 and cisplatin) or VP arm (vinorelbine and cisplatin), with early concurrent thoracic radiotherapy of 60 Gy, comprising 2 Gy per daily fraction. The primary endpoint was the overall survival rate at 2 years (2-year overall survival (OS)) (Study ID: UMIN000002420).
RESULTS: From September 2009 to September 2012, 112 patients were enroled. Of the 108 eligible patients, the 2-year OS was 75.6% (80% confidence interval (CI), 67-82%) in the SP arm and 68.5% (80% CI: 60-76%) in the VP arm. The hazard ratio (HR) for death between the two arms was 0.85 (0.48-1.49). The median progression-free survival was 14.8 months for the SP arm and 12.3 months for the VP arm with an HR of 0.92 (0.58-1.44). There were four treatment-related deaths in the SP arm and five in the VP arm.
CONCLUSIONS: The null hypotheses for 2-year OS were rejected in both arms. The West Japan Oncology Group will employ the SP arm as the investigational arm in a future phase III study.

Hayata K, Ojima T, Nakamori M, et al.
Neoadjuvant Chemotherapy with Docetaxel, Cisplatin and S-1 for Resectable Advanced Esophageal Cancer.
Anticancer Res. 2018; 38(9):5267-5273 [PubMed] Related Publications
BACKGROUND/AIM: Although the efficacy is limited, standard therapy for Stage II/III esophageal cancer in Japan includes neoadjuvant chemotherapy with cisplatin plus 5-fluorouracil. A phase II trial was conducted on patients with resectable advanced esophageal cancer obtaining neoadjuvant chemotherapy with docetaxel, cisplatin plus S-1 (DCS).
PATIENTS AND METHODS: A total of 40 patients were enrolled, each treated by the following DCS regimen: docetaxel 40 mg/m
RESULTS: Clinical response rate was 76% and the pathological response rate (Grade 2/3) was 33%. Hematological toxicities of Grade 3/4 were leukopenia 50%, neutropenia 68%, and febrile neutropenia 18%.
CONCLUSION: Neoadjuvant chemotherapy with DCS is a feasible therapeutic strategy for patients with advanced thoracic esophageal squamous cell carcinoma.

Namikawa T, Ishida N, Tsuda S, et al.
Pathological Complete Response by S-1 Chemotherapy in Advanced Gastric Cancer.
In Vivo. 2018 Sep-Oct; 32(5):1211-1216 [PubMed] Free Access to Full Article Related Publications
A pathological complete response (pCR) to treatment for gastric cancer is a rare event, even when powerful treatment regimens are used. Herein, a case of 61-year-old male referred to our hospital with advanced gastric cancer who achieved a pCR following chemotherapy using S-1, and subsequently underwent total gastrectomy is reported. His initial esophagogastroduodenoscopy (EGD) revealed an irregular, nodular, ulcerated lesion in the upper third of the stomach that was analyzed by biopsy to be a moderately differentiated adenocarcinoma. Abdominal contrast-enhanced computed tomography (CT) showed gastric wall thickening and lymph node swelling in the perigastric area. The patient was clinically diagnosed with cT3N1M0, stage IIB advanced gastric cancer. The patient decided against curative surgery due to his work circumstances and was started on S-1 (80 mg/m

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