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Objective: To evaluate the effect and safety of low-dose of apatinib and S-1 combined with Jianpi Bushen Jiedu Decoction (JBJD) in patients with metastatic colorectal cancer (mCRC) who have failed second or above lines treatment, in order to provide more treatment option for mCRC patients by integrated medicine., Methods: Thirteen patients were selected from a single-arm, open-label clinical study from April 2019 to September 2020. The patients were treated with low-dose apatinib (250 mg, once a day) and S-1 (20 mg, twice a day) combined with JBJD for at least one cycle and were followed up to August 2021. The primary endpoint was disease progression-free survival (PFS). Disease control rate (DCR), objective response rate (ORR), and overall survival (OS) of patients were observed as the secondary endpoints. Adverse events were recorded as well., Results: The average age of the 13 patients was 56.5 ±13.0 years and 76.9% were male. The median PFS and median OS were 4.6 and 8.3 months, respectively. The ORR was 7.7% (1/13) while the DCR was 61.5% (8/13). The common adverse events were hypertension, proteinuria, elevated transaminase, and thrombocytopenia. One patient experienced thrombocytopenia of grade 3., Conclusions: Patients with mCRC after failure of the second or above lines of treatment may potentially benefit from the treatment of low-dose apatinib and S-1 combined with JBJD because of its similar effect as the standard dose of target therapy and relatively better safety. (Registration No. ChiCTR1900022673)., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: For decades, concurrent chemo-radiotherapy with cisplatin-based regimen has been a standard therapy for locally advanced stage III non-small-cell lung cancer (NSCLC). We conducted individual-participant-data (IPD) meta-analyses to compare S-1/cisplatin versus other third-generation anti-cancer medications plus cisplatin regimens with the goal of determining whether or not S-1/cisplatin was the ideal choice for treatment accompanied by radiotherapy (RT)., Methods: A thorough search was performed using multiple electronic databases. We integrated the IPD of each trial and analyzed the resulting meta-database. The primary endpoint was the overall survival (OS), and the secondary endpoints included the progression-free survival (PFS), objective response rate (ORR), toxicities, and treatment delivery. Subgroup analyses were conducted based on baseline characteristics. Statistical analyses were stratified by trials., Results: Three randomized control trials (WJOG5008L study, SPECTRA study, and TORG1018 study) were found. Of the 316 patients enrolled in those studies, 159 received S-1/cisplatin (SP), and 157 were assigned to other combination chemotherapy. The median OS for the SP arm was 48.2 months, and that of the non-SP arm was 42.4 months. The combined hazard ratio (HR) for the OS was 0.895 (95% confidence interval [CI] 0.638-1.256), and no heterogeneity was noted among the trials (test for heterogeneity, p = 0.87; I 2  = 0). The median PFS for the SP and non-SP arms was 12.8 and 14.0 months, respectively. The corresponding HR for the PFS was 1.022 (95% CI 0.776-1.347), and there was evidence of moderate heterogeneity among the trials (test for heterogeneity, p = 0.16; I 2  = 0.46). The ORRs were 69.7% (95% CI 62.1-76.7%) and 70.9% (95% CI 63.7-78.1%) in the SP and non-SP arms, respectively. The toxicity profile showed that SP caused significantly fewer instances of grade 3-4 leukopenia and neutropenia than non-SP regimens., Conclusion: No marked differences were detected in the OS, PFS, or ORR between the SP and non-SP arms. SP had significantly less myelosuppression and better treatment compliance as a chemotherapy regimen for concurrent chemoradiation in locally advanced NSCLC than non-SP regimens., (© 2022. The Author(s).)

Background Combination therapy of gemcitabine with cisplatin (GC) is a standard first-line therapy for unresectable or recurrent biliary tract cancer (BTC). S-1 is often used as a second-line therapy in clinical practice, based on the results of some clinical studies investigating its efficacy and safety following gemcitabine monotherapy. However, few studies have reported on the clinical outcomes of S-1 following GC. The purpose of this study was to elucidate the efficacy and safety of S-1 following GC for unresectable and recurrent BTC. Methods We retrospectively collected the data of 116 patients (pts) who were treated with S-1 as a second-line therapy following GC for unresectable or recurrent BTC at Shizuoka Cancer Center (November 2009 to July 2019). Results Of these 116 pts., 84 were assessable. Patient characteristics were as follows: intrahepatic bile duct/extrahepatic bile duct/gallbladder cancer, 30/23/31 pts.; metastatic/recurrent/locally advanced, 57/17/10 pts. The median time to treatment failure and overall survival were 2.5 and 6.0 months, respectively. Among 65 pts. with measurable lesions, the overall response rate was 3.1% (2/65 pts) and the disease control rate was 24.6% (19/65 pts). The common grade 3/4 toxicities included anemia (12%), neutropenia (4%), infections (16%), fatigue (6%), and diarrhea (4%). Dose reduction or treatment schedule modification of S-1 was required in 29 pts. (34.5%), and 17 pts. (20%) terminated S-1 due to adverse events. Conclusions The efficacy and safety of S-1 following GC were almost the same as those of S-1 following GEM monotherapy for unresectable or recurrent BTC., (© 2021. The Author(s).)

The prognosis of patients with advanced pancreatic cancer is poor. In the present phase I/II study, we have evaluated the safety and the feasibility of Wilms' tumor 1 (WT1) and/or mucin1 (MUC1) peptide-pulsed dendritic cell (DC) vaccination in combination with chemotherapy in patients with advanced or relapsed pancreatic ductal adenocarcinoma (PDAC). Sixty-five eligible patients were enrolled. No severe adverse events related to the vaccinations were observed. Objective response rate and disease control rate was 12.3% and 50.8%, respectively. Median progression-free survival and overall survival were 4.9 and 9.6 months, respectively. DC vaccinations augmented WT1- and MUC1-specific immunity which might be related to clinical outcome. These results indicate that DC-based immunotherapy combined with a conventional chemotherapy is safe and feasible for patients in advanced stage of PDAC., (© 2021 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Introduction In preclinical data, the combination therapy with S-1 and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) had a synergistic antitumor effect on non-small cell lung cancer (NSCLC), regardless of the EGFR mutation status. Patients and Methods Patients with previously treated NSCLC and adequate organ function regardless of EGFR mutation status were eligible for the phase I study, with wild-type EGFR were eligible for the phase II study. Treatment consisted of erlotinib 150 mg/body orally once every day and S-1 60 mg/m 2 , 70 mg/m 2 , or 80 mg/m 2 (level 0, level 1, or level 2) orally on days 1-14 every three weeks. The primary endpoint for the phase I study was the determination of the recommended dose (RD), the phase II study was the overall response rate (ORR). Results A total of 7 patients with performance-status (PS) 0 or 1 were enrolled as subjects in phase I. Five of these subjects were EGFR-mutation positive. Four subjects were enrolled at S-1 dose level 1 and 3 were enrolled at S-1 dose level 2. No dose-limiting toxicities were observed in these subjects. The RD was decided as erlotinib 150 mg/body and S-1 80 mg/m 2 . In phase I, 5 subjects achieved partial response, and the ORR was 71.4%. A total of 10 patients with PS 0, 1, or 2 EGFR-wild type NSCLC were enrolled in phase II. In phase II, the ORR was 10.0%, and the disease control rate (DCR) was 40.0%. After the enrollment of 10 subjects, enrollment was stopped based on two treatment-related deaths. Conclusion The combination therapy of erlotinib plus S-1 was not feasible in the EGFR wild-type NSCLC at least and early stopped. Trial registration: UMIN-CTR Identifier: 000003421 (2010/03/31, phase I), 000003422 (2010/03/31, Phase II).

Background: This study aimed to determine the effect and mechanism of Xiaoaiping (XAP) injection combined with S-1 in inhibiting the invasion and metastasis of human GC cells., Methods: BGC-823 and MGC-803 cells were incubated in vitro, and the effects of treatment on the cytotoxicity and proliferation of BGC-823 and MGC-803 cells were evaluated by MTT assay. Cell adhesion tests and Transwell assays were used to detect the effects of Xiaoaiping injection combined with S-1 on the metastatic ability of BGC-823 and MGC-803 cells. The expression of VEGF, Metalloproteinases (MMPs) and proteins related to the Epithelial-Mesenchymal Transition (EMT) were detected by Western blotting. Meanwhile, a tumour model was established in nude mice, and the effect of XAP combined with S-1 on BGC-823 cells in vivo was studied., Results: Compared with the single drug group, the combination of XAP with S-1 increased the inhibition rate (P<0.05). The adhesion test showed that the combination group significantly inhibited the adhesion of BGC-823 and MGC-803 cells (P<0.05). The combination of XAP with S-1 reduced the migration and invasion potential of human GC BGC-823 and MGC-803 cells. Western blotting showed that the expression of VEGF, MMP-9, Ncadherin and vimentin was decreased and E-cadherin expression was increased in the combination group compared with these expression values in either the XAP or S-1 alone group (P<0.05). In vivo, we found that XAP combined with S-1 had a significant inhibitory effect on the growth of tumours compared with XAP or S-1 alone. Immunohistochemistry showed that XAP combined with S-1 was able to enhance the levels of E-cadherin and downregulate N-cadherin and vimentin., Conclusion: The combination of XAP with S-1 can enhance the inhibitory effect of a single drug on proliferation, invasion and metastasis. The mechanism may be related to the decrease in the expression of VEGF and MMP-9 proteins and the effect on EMT., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The evidence of combining neoadjuvant chemotherapy with targeted therapy for patients with locally advanced gastric cancer is inadequate. We conducted a single-arm phase II trial to evaluate the efficacy and safety of S-1, oxaliplatin and apatinib (SOXA) in patients with locally advanced gastric adenocarcinoma., Methods: Treatment-naïve patients received three preoperative cycles of S-1 (80-120 mg/day on days 1-14) and oxaliplatin (130 mg/m 2 on day 1) and two cycles of apatinib (500 mg/day for 21 days) at 3-week intervals, followed by surgery. The primary end-point was pathologic response rate (pRR). This trial is registered at ChiCTR.gov.cn: ChiCTR-OPC-16010061., Results: Of 29 patients included, median age was 60 (range, 43-73) years; 20 (69.0%) were male. The pRR was 89.7% (95% confidence interval [CI], 72.7%-97.8%; 26 of 29 patients; P < 0.001) with 28 patients treated with surgery. All 29 patients were available for preoperative response evaluation, achieving an objective response rate of 79.3% (95% CI, 60.3%-92.0%) and a disease control rate of 96.6% (95% CI, 82.2%-99.9%). The margin-free resection rate was 96.6% (95% CI, 82.2%-99.9%). The pathologic complete response rate was 13.8% (95%CI, 1.2%-26.3%). Downstaging of overall TNM stage was observed in 16 (55.2%) patients. During neoadjuvant therapy, 10 (34.5%) patients had grade ≥III adverse events. No treatment-related death occurred. Surgery-related complications were observed in 12 of 28 (42.9%) patients., Conclusion: SOXA followed by surgery in patients with locally advanced gastric adenocarcinoma showed favourable activity and manageable safety. A randomised controlled trial in locally advanced gastric or oesophagogastric junction adenocarcinoma is ongoing (ClinicalTrials.gov: NCT04208347)., Competing Interests: Conflict of interest statement All authors declare that they have no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: S-1 combined with cisplatin is known to be noninferior to taxanes plus platinum as the first-line treatment for patients with advanced nonsmall cell lung cancer (NSCLC) in the Japanese population. This study aimed to evaluate the efficacy and safety profiles of oral S-1 plus cisplatin (SP) in Taiwanese patients., Methods: Patients with previously untreated stage IIIB or IV NSCLC were prospectively recruited to receive 40-60 mg of S-1 twice daily on days 1-21 plus 60 mg/m 2 of cisplatin on day 8 in a 5-week cycle for up to six cycles., Results: A total of 55 patients from five cancer centers in Taiwan were enrolled. Among the 46 evaluable patients, those administered with SP achieved disease control rate of 69.6% (partial response, 19.6%; stable disease, 50.0%), with median overall survival and progression-free survival (PFS) of 15.1 and 5.7 months, respectively. Moreover, a better survival trend was observed in epidermal growth factor receptor mutation-positive patients versus mutation-negative patients treated with SP (PFS, 8.6 vs 5.6 months). The most commonly observed treatment-related adverse events (AEs) were nausea (41.8%), followed by decreased appetite, anemia, and diarrhea. Grade of ≥3 AEs related to the study treatment occurred in 11 patients (20.0%). No febrile neutropenia or treatment-related death was found in this study., Conclusions: This study demonstrated that SP is an effective and safe first-line regimen for Taiwanese patients with advanced NSCLC., (© 2019 John Wiley & Sons Australia, Ltd.)

Background Esophageal cancer is a very common malignant tumor in China, especially esophageal squamous cell carcinoma (ESCC), but there is currently no effective treatment for patients after first-line chemotherapy failure. Apatinib has shown promising outcomes in treatment with various solid tumors. Objectives To evaluate the clinical efficacy and safety of apatinib combined with S-1 in the treatment of advanced ESCC patients after first-line chemotherapy failure. Methods In this prospective study, fifteen patients with advanced ESCC who failed first-line chemotherapy were enrolled from Nov 2016 to Apr 2019. Patients received the combination therapy with apatinib (250-500 mg, once daily) plus S-1 (40-60 mg based on body surface area, twice daily). Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), disease control rate (DCR) and objective response rate (ORR). Adverse events (AEs) were recorded to evaluate the safety. Results A total of 12 patients were included in the efficacy analysis. The median PFS was 6.23 months, and the median OS was 8.83 months. Two (16.67%) patients achieved partial remission, 9 patients (75.00%) achieved stable disease and 1 (8.33%) patient achieved progressive disease. DCR and ORR was 91.67%and 16.67%, respectively. Most frequent AEs were hypertension, myelosuppression, weakness, hemorrhage, hand-foot syndrome, total bilirubin elevation, sick, proteinuria, oral ulcer, loss of appetite, and transaminase elevation. The most AEs were in grade I~II. Conclusion The combination therapy of apatinib plus S-1 was effective and well tolerated in the treatment of advanced ESCC patients after first-line chemotherapy failure. The combination therapy has the potential to be a potent therapeutic option for advanced ESCC patients after first-line chemotherapy failure.

Purpose: In advanced gastric cancer, peritoneal dissemination is a life-threatening mode of metastasis. Since the treatment options with conventional chemotherapy remain limited, any novel therapeutic strategy that could control such metastasis would improve the outcome of treatment. We recently developed a unique RNA interference therapeutic regimen (DFP-10825) consisting of short hairpin RNA against thymidylate synthase (TS shRNA) and cationic liposomes. The treatment with DFP-10825 has shown remarkable antitumor activity in peritoneally disseminated human ovarian cancer-bearing mice via intraperitoneal administration. In this study, we expanded DFP-10825 to the treatment of peritoneally disseminated gastric cancer., Methods: DFP-10825 was administered intraperitoneally into mice with intraperitoneally implanted human gastric cancer cells (MKN45 or NCI-N87). Antitumor activity and host survival benefits were monitored. Intraperitoneal distribution of fluorescence-labeled DFP-10825 was monitored in this MKN45 peritoneally disseminated mouse model., Results: Intraperitoneal injection of DFP-10825 suppressed tumor growth in two peritoneally disseminated cancer models (MKN45 and NCI-N87) and increased the survival time of the MKN45 model without severe side effects. Throughout the treatment regimen, no significant body weight loss was associated with the administration of DFP-10825. Interestingly, after intraperitoneal injection, fluorescence-labeled DFP-10825 retained for more than 72 hours in the peritoneal cavity and selectively accumulated in disseminated tumors., Conclusions: Intraperitoneal injection of DFP-10825 demonstrated effective antitumor activity without systemic severe adverse effects via the selective delivery of RNAi molecules into disseminated tumors in the peritoneal cavity. Our current study indicates that DFP-10825 could become an alternative option to improve the outcomes of patients with peritoneally disseminated gastric cancer., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: S-1 is an oral fluoropyrimidine anticancer drug consisting of the 5-fluorouracil prodrug tegafur combined with gimeracil and oteracil. The purpose of this study was to evaluate the pharmacokinetic (PK), bioequivalence, and safety of a newly developed generic formulation of S-1 compared with the branded reference formulation, in Korean gastric cancer patients., Methods: This was a single-center, randomized, open-label, single-dose, two-treatment, two-way crossover study. Eligible subjects were randomly assigned in a 1:1 ratio to receive the test formulation or reference formulation, followed by a one-week washout period and administration of the alternate formulation. Serial blood samples were collected at 0 hrs (predose), 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hrs after dosing in each period. The plasma concentrations of tegafur, 5-FU, gimeracil, and oteracil were analyzed using a validated liquid chromatography-tandem mass spectrometry method. The PK parameters were calculated using a non-compartmental method., Results: In total, 29 subjects completed the study. All of the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) fell within the predetermined acceptance range. No serious adverse events were reported during the study., Conclusion: The new S-1 formulation met the Korean regulatory requirement for bioequivalence. Both S-1 formulations were well tolerated in all subjects. Clinical trial registry: https://cris.nih.go.kr CRIS KCT0003855., Competing Interests: At the time of the study, KC was employed by Biocore Co. Ltd. and YKS was employed by Myungmoon Pharm. Co., Ltd. The authors report no other conflicts of interest in this work., (© 2019 Lee et al.)

Objectives: Platinum-based combination chemotherapy is the standard postoperative adjuvant treatment for pathological stage II/III non-small cell lung cancer (NSCLC). Oral S-1 therapy has good efficacy and relatively low toxicity for the treatment of advanced NSCLC. We investigated whether long-term S-1 monotherapy is also useful as an adjuvant therapy after surgery in patients with NSCLC., Patients and Methods: We conducted a phase II randomized open-label multi-institutional study in patients with pathological stage II/IIIA NSCLC (7 th TNM classification) who underwent complete resection from 2009 to 2013. The primary endpoint, the 2-year disease-free survival (DFS) rate, was evaluated using the Bayesian method. Eligible patients were randomly assigned to two arms: oral S-1 monotherapy (S-1 arm) and S-1 plus cisplatin combination therapy followed by S-1 (S-1 plus cisplatin arm) both for a total of 1 year., Results: A total of 70 and 71 patients were enrolled in S-1 arm and S-1 plus cisplatin arm, respectively. The 2-year DFS rates were 52% (95% confidence interval [CI], 0.40-0.63) and 61% (95% CI, 0.48-0.70) for S-1 arm and S-1 plus cisplatin arm, respectively. Both arms met the primary endpoint. Neither DFS nor OS was significantly different between the arms (log-rank test: P =  0.1695 and P =  0.8684, respectively). The main G3/4 adverse events were loss of appetite and anemia (S-1 vs. S-1 plus cisplatin: 4.3% vs. 11.6% and 0% vs. 5.8%, respectively). The treatment completion rate did not differ between the two arms (S-1 vs. S-1 plus cisplatin: 45.7%, 95% CI, 41.9-66.3% vs. 43.5% 95% CI, 44.0-68.4%)., Conclusions: Long-term adjuvant chemotherapy with S-1 was a feasible and promising treatment for patients with completely resected NSCLC, regardless of cisplatin addition. S-1 monotherapy should be investigated further, based on its low toxicity and practical convenience., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: There is no standard treatment for advanced non-small cell lung cancer (NSCLC) after the failure of two lines of chemotherapy, S-1 as the third generation of fluorouracil derivate with well safety and low toxicity, presented some efficacy in lung cancer treatment. The aim of this study is to explore the efficacy of S-1 for advanced NSCLC patients treated with two or more prior chemotherapy regimens., Methods: We performed a retrospective analysis of 105 NSCLC patients treated with S-1 monotherapy or S-1 contained chemotherapy as the third or more line of treatment in our hospital from January 2014 to April 2017. S-1 was administrated orally twice daily for 2 weeks, followed by one week of rest, the dose of drug was determined by body surface area (<1.25 m2, 80 mg/d; 1.25 m2-1.5 m2, 100 mg/d; ≥1.5 m2, 120 mg/d), platinum or the third-generation chemotherapy drugs could be combinedly used. Clinical response was assigned every cycle according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Kaplan-Meier analysis was used to estimate progression-free survival (PFS)., Results: 42 patients received S-1 monotherapy, the other 63 patients received combined regimens, the median treatment line was 4 (3-11) and the median treatment cycle was 2 (1-14). No complete response (CR) were observed, there were 4 patients with partial response (PR), 34 patients with stable disease (SD) and 67 patients with progressive disease (PD), the objective response rate (ORR) was 3.81%, disease control rate (DCR) was 36.19%. The median PFS was 1.90 months (0.67 months-10.83 months), no difference between monotherapy and combined group (DCR: 28.56% vs 41.27%, P=0.185), the liver metastasis showed poorer PFS (1.40 months vs 1.93 months , P=0.042)., Conclusions: S-1 presented some activity in advanced NSCLC treated with more than two lines of treatment. The addition of other drugs cannot improve efficacy. S-1 monotherapy can be used as a choice for heavily-treated patients.

Background/aim: A phase 3 trial of S-1, leucovorin (LV), and oxaliplatin for treating gastric cancer is now underway. However, the antitumor efficacy of the combination has not yet been examined in an in vivo preclinical study. This study examined the antitumor efficacy of combination therapy consisting of S-1, LV, and oxaliplatin against 4 human gastric cancer xenografts: NUGC-4, St-40, SC-2, and SC-4., Methods: The antitumor efficacy was evaluated using human gastric cancer xenograft-bearing nude mice. S-1 and LV were administered orally once daily on days 1-7 at doses of 6.9 and 10 mg/kg, respectively. Oxaliplatin was administered intravenously at a dose of 8.3 mg/kg on day 1. The tumor volume was measured on day 15, and the relative tumor volume (RTV) was calculated., Results: In all 4 xenograft models, S-1 alone and oxaliplatin alone, but not LV alone, had significant antitumor activities (p < 0.001). Combination therapy consisting of S-1 and LV resulted in a significantly smaller RTV than S-1 alone (p < 0.001). Combination therapy consisting of S-1 and oxaliplatin also resulted in a significantly smaller RTV than either S-1 alone (p < 0.001) or oxaliplatin alone (p < 0.001). Furthermore, combination therapy consisting of S-1, LV, and oxaliplatin resulted in the highest antitumor activity in these models (p < 0.001 vs. S-1 + LV; p < 0.001 or p = 0.003 vs. S-1 + oxaliplatin)., Conclusion: Combination therapy consisting of S-1, LV, and oxaliplatin administered according to a 1-week-on/1-week-off schedule may be useful for the treatment of patients with gastric cancer., (© 2018 S. Karger AG, Basel.)

Purpose: A high proportion of patients with wild-type EGFR non-small cell lung cancer (NSCLC) receive third-line therapy and beyond, with no prospective randomized trials addressing the issue. This study aimed to select the most suitable regimen as a third- or fourth-line therapy for wild-type EGFR NSCLC., Methods: This multicenter, randomized phase II study in Japan included patients with recurrent or advanced NSCLC with wild-type or unknown EGFR, who progressed after two or three previous chemotherapies. The patients were randomly assigned to erlotinib (150 mg/day, days 1-21) or S-1 (80-120 mg/day, days 1-14) every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was disease control rate (DCR). The secondary endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), toxicity, and quality of life (QOL)., Results: From 2011 to 2016, 37 patients were randomly assigned to receive erlotinib (E arm, n = 19) and S-1 (S arm, n = 18). This study was terminated prematurely because of poor patient accrual. DCR/ORR were 42.1%/15.8% in the E arm and 66.7%/16.7% in the S arm. Median PFS/OS were 1.6 months/8.0 months in the E arm and 3.3 months/12.2 months in the S arm. In both groups, the most commonly reported grade 3-4 toxicities were fatigue, anorexia, and nausea. One grade 5 pneumonitis occurred in the S arm. No significant difference was seen in QOL., Conclusions: S-1 as a third- or fourth-line therapy for wild-type EGFR NSCLC showed numerically better clinical outcomes than erlotinib., Clinical Trial Registration No: UMIN000005308.

Background: Lentinan (LNT) is a purified β-1, 3-glucan that augments immune responses. The present study was conducted to assess the efficacy of LNT in combination with S-1 as a first-line treatment for unresectable or recurrent gastric cancer., Patients and Methods: Eligible patients were randomly assigned to receive S-1 alone or S-1 plus LNT. The primary end-point was overall survival (OS). Secondary end-points were time-to-treatment failure (TTF), overall response rate (ORR), safety, quality of life (QOL), and biomarker. The percentages of LNT-binding monocytes in peripheral blood prior to treatment were analysed for the biomarker assessment., Results: One hundred and fifty-four and 155 patients were randomly assigned to receive S-1 alone or S-1 plus LNT, respectively. The median OS was 13.8 and 9.9 months (P = 0.208), the median TTF was 4.3 and 2.6 months (P < 0.001), the ORR was 22.3% and 18.7% for the S-1 and S-1 plus LNT groups, respectively. The incidences of haematologic and non-haematologic adverse events were similar, and no significant changes in QOL scores were observed during the treatment in both groups. In a subpopulation of patients with LNT-binding monocytes ≥2%, patients who received more than two cycles of chemotherapy showed a longer survival time in the S-1 plus LNT group., Conclusions: OS did not improve and TTF was significantly worse in the S-1 plus LNT group as compared with the S-1-only group. This study showed no efficacy of LNT when combined with S-1 treatment in patients with unresectable or recurrent gastric cancer., Clinical Trial Registration Id Number: UMIN 000000574., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Concurrent chemoradiotherapy (CCRT) is the preferred treatment for stage III unresectable non-small cell lung cancer (NSCLC). However, there have been few reports on combination chemotherapy with radiation for second- and third-generation antitumor drugs, although clinical guidelines have recommended the use of these drugs along with platinum agents., Methods: We retrospectively analyzed the efficacy and toxicity of cisplatin and either S-1 or vinorelbine for treating stage III unresectable NSCLC patients who were treated with CCRT., Results: Between September 2006 and May 2014, 56 patients with unresectable stage III NSCLC were treated with CCRT with S-1 and cisplatin (median age: 63 years) and 58 patients were treated with CCRT with vinorelbine and cisplatin (median age: 61 years). The median follow-up time was 14.6 months in the S-1 arm and 28.0 months in the vinorelbine arm. We found no significant difference in progression-free survival (15.8 months vs. 10.1 months; p=0.15) and overall survival (33.7 months vs. 31.1 months; p=0.63) between the S-1 and vinorelbine arms, respectively. Severe (more than grade 3) leukopenia (35.7% vs. 98.2%; p<0.01), neutropenia (44.6% vs. 98.2%; p<0.01), and febrile neutropenia (1.8% vs. 46.6%, p<0.01) were significantly less frequent in the S-1 arm than in the vinorelbine arm. Treatment-related deaths were not observed in either arm., Conclusions: CCRT with both S-1 or vinorelbine with cisplatin appears feasible based on their efficacy and toxicity profiles. Both treatments may be recommended as treatment options for patients with stage III unresectable NSCLC., (Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

of Background Data The effectiveness of adjuvant chemotherapy in patients with stage II/III colorectal cancer has been confirmed in various studies. However, no adjuvant chemotherapy for colorectal liver metastasis (CLM) classified to stage IV has been established. Objectives We conducted a phase 1 study of S-1 and oxaliplatin to determine the recommended dose (RD) in patients with CLM as adjuvant therapy in two institutes. Methods S-1 and oxaliplatin were administered from day 1 to day 14 of a 3-week cycle as a 2-h infusion every 3 weeks, respectively. The initial doses of S-1 and oxaliplatin were fixed to 80 mg/m(2) and 100 mg/m(2), respectively (level 1). We scheduled in the protocol a dose change of S-1 and oxaliplatin to level 2 (S-1: 80 mg/m(2) and oxaliplatin: 130 mg/m(2)) or level 0 (S-1: 65 mg/m(2) and oxaliplatin: 100 mg/m(2)) depending on the incidence of dose-limiting toxicity (DLT) at level 1 in six patients. Results Because DLT occurred in one among the initial six patients at level 1, the doses were increased to level 2 in the next six patients. At level 2, grade 3 leukopenia and neutropenia occurred in one (16.7 %) and two (33.3 %) patients, respectively, in the absence of non-hematological event. Because no DLT occurred at level 2, we suggest that the RD can be set to the level 2 dose. The median number of cycles delivered at RD was 8. The mean relative dose intensity of S-1 and oxaliplatin at RD was 0.90 and 0.63, respectively. Conclusion In a patient undergoing hepatectomy for CLM, 80 mg/m(2) of S-1 and 130 mg/m(2) of oxaliplatin are recommended as adjuvant therapy. A further study is required to confirm the efficacy and safety of this regimen on a larger scale.

Objectives Maintenance therapy is a standard therapeutic strategy in non-squamous non-small-cell lung cancer. However, there is no consensus regarding the benefit of maintenance therapy for patients with squamous cell lung cancer. We assessed maintenance therapy with S-1, an oral fluoropyrimidine agent, following induction therapy with carboplatin and S-1 in patients with squamous cell lung cancer. Methods In this phase II trial, chemotherapy-naïve patients with squamous cell lung cancer were enrolled to induction therapy with four cycles of carboplatin (at an area under the curve of 5 on day 1) and S-1 (80 mg/m(2)/day on days 1-14) in a 28-day cycle. Patients who achieved disease control after induction therapy received maintenance therapy with S-1 in a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival after administration of maintenance therapy. Results Fifty-one patients were enrolled in the study. The median progression-free survival from the start of maintenance therapy was 3.0 months (95 % confidence interval, 2.5-3.5). The most common toxicities associated with maintenance therapy were anemia, thrombocytopenia, and fatigue, but they were not severe. Conclusion S-1 maintenance therapy might be a feasible treatment option in patients with squamous cell lung cancer.

Purpose: Pre-existing interstitial lung disease (pre-ILD) increases the risk of chemotherapy-related lung injury (CRLI). However, whether the risk varies by type of anti-cancer cytotoxic agent in patients with pre-ILD is unknown. In this study, we hypothesized that S-1, an oral fluoropyrimidine agent, is associated with a smaller CRLI risk than docetaxel (DTX) and investigated these agents together with radiological evaluations of pre-ILD via pre-treatment chest computed tomography (CT)., Methods: After reviewing 234 and 352 patients who underwent evaluable chest CT within 6 months prior to the administration of S-1 or DTX, respectively, from January 2006 to October 2014, 60 and 89, respectively, of these patients with pre-ILD were retrospectively analysed., Results: In total, 2 persons administered S-1 (3 %) and 16 treated with DTX (18 %) developed CRLI (p = 0.007) after the initial treatment (mean, 61 days), of whom 1 and 7, respectively, died because of respiratory failure. Pre-treatment CT revealed that 9 S-1-treated patients (16 %) and 15 DTX-treated patients (17 %) had pre-ILD occupying more than 25 % of the lung field. Multivariate analysis demonstrated that DTX administration increased the risk of CRLI by 6.47-fold versus S-1 therapy (p = 0.016). Of note, the area occupied by pre-ILD was also associated with the risk of CRLI (<25 %; odds ratio 0.309, p = 0.045)., Conclusions: Our results indicated that S-1 is associated with a smaller risk of CRLI than DTX. The area occupied by pre-ILD should also be noted when administrating anti-cancer agents.

Background: S-1, an oral 5-fluorouracil (5-FU)-based medicine that combines tegafur, gimeracil and oteracil potassium is commonly used as an adjuvant chemotherapeutic drug for the treatment of colorectal cancer., Patients and Methods: We enrolled 53 patients who underwent curative resection for colorectal cancer and liver metastasis (synchronous, n=24; metachronous, n=29). The subsequent adjuvant chemotherapy with oral S-1 administration was initiated within 56 days after liver resection. Recurrence was evaluated by imaging studies, that were performed during the first year after liver resection. Of the 53 patients, 25 who did not recur within 1 year were defined as being in the no-recurrence (NREC) group and the remaining 18 patients were defined as being in the early-recurrence (EREC) group. There were no significant differences in gene expression profiling for drug resistance and metabolism between the NREC group and the EREC group., Results: In synchronous liver metastasis, there was no significant difference in early recurrence between serum carcinoembryonic antigen (CEA) ≤5 ng/ml and serum CEA >5 ng/ml (8/24 vs. 16/24, respectively). In metachronous liver metastasis, the early recurrence rate was significantly higher in patients with CEA >5 ng/ml compared to patients with CEA ≤5 ng/ml (15/29 vs. 14/29, p=0.05). The expression of cytochrome P450 2C19 (CYP2C19) and ATP-binding cassette, sub-family B member 1 (ABCB1) were significantly lower in the EREC group (6/15) compared to the NREC group (9/15) in colorectal cancer with metachronous liver metastasis and with serum CEA >5 ng/ml., Conclusion: Although the exact reason for down-regulation of these genes in the group with poor prognosis is unknown, the information obtained in this study may be useful in clinical practice for colorectal cancer., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: The potential of S-1 for the treatment of metastatic renal cell carcinoma (mRCC) has been shown in two phase II studies. We aimed to assess the safety, tolerance, pharmacokinetics and clinical activity of S-1 combined with sorafenib in patients with mRCC., Patients and Methods: In this multicenter, single-arm, open-label, phase I/II study of S-1 plus sorafenib, we recruited patients with clear-cell or papillary renal cell carcinoma who had received a maximum of one prior cytokine-based regimen. The phase I primary end points were the maximum tolerated dose (MTD) and recommended dose (RD). S-1 was administered orally at 60, 80, 100 or 120 mg/day on days 1-28 of a 42-day cycle in combination with sorafenib (400 or 800 mg/day), given daily with dose adjustment. In phase II, the primary end point was to assess the overall response rate (ORR) at the RD., Results: Nine patients were enrolled into phase I and 21 (including 6 patients who received the RD in the phase I portion) were enrolled into phase II. In the phase I portion, the MTD could not be determined, and the RD was defined as S-1 80 mg/m(2)/day on days 1-28 + sorafenib 800 mg/day on days 1-42. In the phase II portion, 21 patients were fully assessable for efficacy and safety. The confirmed ORR was 52% [95% confidence interval (CI) 29.8-74.3], including one complete response (5%) and 10 partial responses (48%). The median progression-free survival was 9.9 (95% CI 6.5-17.1) months. The most frequently reported treatment-related adverse event for all grades was hand-foot skin reaction (100%). The major reasons for dose reduction were hand-foot skin reaction (38%) and rash (14%)., Conclusion: Combination therapy with S-1 plus sorafenib is effective and tolerable for patients with mRCC. However, skin events management is important in S-1 plus sorafenib combination therapy., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Conclusion: Nedaplatin and S-1 treatment with concurrent radiotherapy was effective, with acceptable toxicities. This regimen does not require extensive intravenous hydration and continuous infusion. Nedaplatin and S-1 may contribute to better clinical outcomes and improve quality of life for patients., Objectives: We retrospectively analyzed the clinical efficacy and toxicity of concurrent chemoradiotherapy with nedaplatin and S-1 for head and neck squamous cell cancer., Methods: Forty-six patients with oropharyngeal, hypopharyngeal, and laryngeal cancer were treated with S-1 on days 1 through 14 and nedaplatin on day 1 every 4 weeks for two cycles of radiotherapy. Therapeutic responses and adverse events were assessed., Results: Primary site tumors and neck lymph nodes exhibited complete response rates of 91% and 64.3%, respectively. The 4-year relapse-free survival and overall survival rates were 76.2% and 85.3%, respectively. The main grade 3 and 4 toxicities were mucositis (30%), leukopenia (30%), anorexia (22%), dermatitis (15%), and thrombocytopenia (9%).

Background: We evaluated the efficacy and safety of S-1 plus oxaliplatin (SOX) as an alternative to cisplatin plus S-1 (CS) in first-line chemotherapy for advanced gastric cancer (AGC)., Patients and Methods: In this randomized, open-label, multicenter phase III study, patients were randomly assigned to receive SOX (80-120 mg/day S-1 for 2 weeks with 100 mg/m(2) oxaliplatin on day 1, every 3 weeks) or CS (S-1 for 3 weeks with 60 mg/m(2) cisplatin on day 8, every 5 weeks). The primary end points were noninferiority in progression-free survival (PFS) and relative efficacy in overall survival (OS) for SOX using adjusted hazard ratios (HRs) with stratification factors; performance status and unresectable or recurrent (+adjuvant chemotherapy) disease., Results: Overall, 685 patients were randomized from January 2010 to October 2011. In per-protocol population, SOX (n = 318) was noninferior to CS (n = 324) in PFS [median, 5.5 versus 5.4 months; HR 1.004, 95% confidence interval (CI) 0.840-1.199; predefined noninferiority margin 1.30]. The median OS for SOX and CS were 14.1 and 13.1 months, respectively (HR 0.958 with 95% CI 0.803-1.142). In the intention-to-treat population (SOX, n = 339; CS, n = 337), the HRs in PFS and OS were 0.979 (95% CI 0.821-1.167) and 0.934 (95% CI 0.786-1.108), respectively. The most common ≥grade 3 adverse events (SOX versus CS) were neutropenia (19.5% versus 41.8%), anemia (15.1% versus 32.5%), hyponatremia (4.4% versus 13.4%), febrile neutropenia (0.9% versus 6.9%), and sensory neuropathy (4.7% versus 0%)., Conclusion: SOX is as effective as CS for AGC with favorable safety profile, therefore SOX can replace CS., Clinical Trial Number: JapicCTI-101021., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: S-1 is an oral fluoropyrimidine derivative, including three pharmacological compounds: tegafur, gimeracil and oteracil, in a molar ratio of 1: 0.4: 1., Areas Covered: This review addresses the clinical evidence of S-1 in NSCLC in various clinical settings. Currently, S-1 for NSCLC is approved only in Japan. Prospective studies of S-1 as front-line and second-line chemotherapy with or without other agents and concurrent chemoradiotherapy are mainly reviewed. Only two Phase III clinical trials were published or presented for advanced NSCLC. S-1 and cisplatin is an active first-line chemotherapy regimen for advanced NSCLC and S-1 and carboplatin is noninferior to a carboplatin and paclitaexel regimen. The combination of S-1 and a platinum agent is active against NSCLC, regardless of tumor histology., Expert Opinion: It is becoming possible to design effective regimens with S-1 against NSCLC in various clinical settings considering the ethnic differences in pharmacokinetics and a greater understanding of the underlying molecular pathways or biomarkers of NSCLC. Further Phase III studies with S-1 for both early and advanced NSCLC are warranted worldwide.

Introduction: S-1 is an oral fluoropyrimidine that consists of tegafur, 5-chloro-2, 4-dihydroxypyridine and potassium oxonate. It has been developed as a prodrug of 5-fluorouracil with the goal of improving therapeutic efficacy and tolerability., Areas Covered: This review aims to provide an evidence-based update of clinical trials that have investigated the clinical efficacy, adverse-event profile, dosage and administration of S-1, given alone or in combination with conventional chemotherapeutics and new target-oriented drugs, in the management of colorectal cancer (CRC). Additionally, differences in the tolerability and pharmacokinetics of S-1 between Caucasians and Asians have been described. Finally, the therapeutic efficacy of S-1 regarding metastatic CRC or postoperative CRC has been discussed. Available data have stimulated further research, including Phase III trials for the treatment of advanced CRC., Expert Opinion: Treatment using S-1 combined with oxaliplatin (± bevacizumab) and irinotecan has achieved promising results in terms of feasibility, safety and effectiveness. Furthermore, S-1 is an acceptable treatment as adjuvant chemotherapy for colon cancer.

Whether S-1 could replace 5-Fluorouracil (5-Fu) or not in the treatment of advanced gastrointestinal (GI) cancer (including advanced gastric cancer [AGS] and metastatic colorectal cancer [mCRC]) in Asian patients has been controversial. This meta-analysis was performed to compare the activity, efficacy and toxicity of S-1-based versus 5-Fu-based chemotherapy in those Asian patients. Randomized controlled trials (RCTs) were identified by electronic search of Pubmed. Relevant abstracts were manually searched to identify relevant trials. A total of 2182 patients from eight RCTs were included, and our results demonstrated that S-1-based chemotherapy significantly improved overall survival (OS) (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.77-1.00) and overall response rate (ORR) (odds ratio [OR], 1.72; 95% CI, 1.09-2.70), but no significant progression-free survival (PFS) benefit was found between arms (HR, 0.87; 95% CI, 0.72-1.06). Subgroup analyses revealed that S-1-based chemotherapy significantly improved OS and ORR in subgroups of patients with non-platinum containing regimens (P = 0.041; P = 0.034) and patients with no prior chemotherapy history (P = 0.025; P = 0.016). Statistically significant improvements of PFS and ORR in the S-1-based chemotherapy were observed in the subgroup of patients with AGC (P < 0.001; P = 0.005). S-1-based chemotherapy was characterized by significantly higher incidences of diarrhea, fatigue and thrombocytopenia, and a lower incidence of nausea. This analysis provided strong evidence for survival benefits of S-1, and S-1-based chemotherapy could be considered to replace 5-Fu-based therapy for the treatment of advanced GI cancer in Asian patients., (© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.)

Background: Hilar cholangiocarcinoma is an uncommon cancer and its overall incidence is increasing. Photodynamic therapy (PDT) has been proposed as palliative management for unresectable hilar cholangiocarcinoma (UHC). To date, little is known about the role of the addition of systemic chemotherapy to PDT for UHC. We performed a prospective, randomised, phase II trial to compare PDT plus S-1 and PDT alone for UHC., Methods: Patients with UHC were randomly assigned (in a 1:1 ratio) to PDT plus S-1 or PDT alone. The primary end-point was overall survival. The secondary end-points were progression-free survival, complications, re-intervention rate and quality of life. This trial is registered with clinicalTrials.gov, number NCT00869635., Findings: Between February 2009 and May 2012, we randomly assigned 21 patients to receive PDT plus S-1 and 22 to receive PDT alone. The UHC patients treated with PDT plus S-1 showed higher 1-year survival rate compared with the patients treated with PDT alone (76.2% versus 32%, P=0.003) and prolonged overall survival (median 17 months, 95% confidence interval [CI]: 12.6-21.4, versus 8 months, 95% CI: 6-10, P=0.005, hazard ratio [HR], 0.36; 95% CI: 0.17-0.75). Regarding the secondary end-points, PDT plus S-1 was associated with prolonged progression-free survival compared with PDT alone (median 10 months [95% CI: 4.1-16] versus 2 months [95% CI: 0.4-3.5], P=0.009 (HR for progression 0.39, 95% CI: 0.19-0.83). There were no differences in the number of PDT sessions, the frequency of cholangitis, overall adverse events or the quality of life in either group., Interpretations: PDT plus S-1 was well tolerated and was associated with a significant improvement of overall survival and progression-free survival compared with PDT alone in patients with UHC. These findings warrant further clinical investigation of PDT plus S-1 in patients with UHC., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

We recently reported that combination therapy with metronomic S-1 dosing and oxaliplatin (l-OHP)-containing PEGylated liposomes improved antitumor activity in a murine colorectal tumor model. However, little is known about the mechanism underlying such improved therapeutic efficacy. Here we investigated the impact of combined treatment on biodistribution, tumor accumulation and intratumor distribution of test PEGylated liposomes and on the structure of tumor vasculature in a solid tumor. The combined treatment clearly enhanced tumor accumulation and intratumor distribution of a subsequent test dose of PEGylated liposome as a result of on the one hand prolonging blood circulation of test liposome and on the other hand the alteration in tumor microenvironment. The l-OHP-containing PEGylated liposomes contributed predominantly to the enhanced tumor accumulation and altered tumor distribution of test liposome. On the other hand, metronomic S-1 dosing contributed to the altered tumor distribution but not the tumor accumulation of test liposome. The antitumor effect of the combined treatment, reflected by the proportion of apoptotic cells in the tumor, was approximately equally accounted for by each of the two treatments, leading to a roughly additive effect. In conclusion, 1-OHP-containing PEGylated liposome together with S-1 enhanced intratumor influx, leading to improved antitumor activity of subsequently injected 1-OHP-containing PEGylated liposomes and/or S-1. This strategy we propose, which is clinically applicable, may overcome the problems related to the use of EPR effect-based nanocarrier systems., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Aim: To evaluate the effects and safety of combination chemotherapy with oxaliplatin (L-OHP) and S-1 (SOX regimen) in older patients with advanced gastric cardiac adenocarcinoma (GCA)., Methods: Seventy patients with advanced GCA were classified according to age into an older group (≥ 75 years) and a control group (< 75 years). The SOX regimen was administered to the two groups as follows: S-1 (40 mg/m² po bid) on days 1 to 14 followed by a 7-d off period, plus L-OHP (65 mg/m² iv) for 2 h on days 1 and 8 of a 21-d cycle. This regimen was repeated for four to six cycles. Response and swallow statuses were evaluated after two cycles (6 wk). Effects and toxicity were evaluated four weeks after chemotherapy was completed., Results: The response rate was 65.6% (21/32) in the older group and 68.4% (26/38) in the control group (χ² = 0.062 and P = 0.804). Improvement in swallowing was 78.1% (25/32) in the older group and 76.3% (29/38) in the control group (χ² = 0.032 and P = 0.857). Efficacy was 68.8% (22/32) in the older group and 65.8% (25/38) in the control group (χ² = 0.069 and P = 0.793). Toxicities were reversible and similar in both groups (P > 0.05)., Conclusion: The SOX regimen is an effective, safe and well-tolerated regimen for older patients with advanced GCA.

Background: Interstitial pneumonia is a group of pathologies affecting the pulmonary interstitium, characterized by interstitial fibrosis and extensive alveolar consolidation. This disease can extend to the surrounding blood vessels and pulmonary interstitium, sometimes affecting the entire lung, resulting in functional limitations, including restrictive ventilatory defect, impaired gas exchange, and hypoxemia. Severe interstitial pneumonia can lead to death. Antitumor drugs can induce interstitial pneumonia. Sintilimab is an immune checkpoint inhibitor, a recombinant fully human immunoglobulin G-type programmed death protein-1 monoclonal antibody inhibitor. S-1 is a compound preparation consisting of gimeracil, oteracil potassium, and ftorafur. There have been cases of interstitial pneumonia caused by treatment with sintilimab or S-1 in clinical settings, but no cases of interstitial pneumonia caused by treatment with a combination of sintilimab and S-1 have been reported. Case report: A patient diagnosed with gastric cancer underwent nine courses of treatment using a chemotherapy regimen of combined oxaliplatin S-1., Due to severe bone marrow suppression and gastrointestinal adverse reactions, the treatment was switched to sintilimab in combination with S-1therapy., This change resulted in the development of interstitial pneumonia, as revealed by non-contrast chest Computed Tomography scans. Following a review of blood test results and a multidisciplinary consultation, we suspect that the interstitial pneumonia may have been caused either by Sintilimab alone or by the combined effects of sintilimab and S-1. The treatment was discontinued, and after receiving adequate glucocorticoid therapy, the pulmonary lesions showed slight improvement. Conclusion: This case provides a clinical reference, indicating that prior touse of sintilimab in combination with S-1 antitumor regimen, a comprehensive baseline assessment should be conducted, including blood routine examination, enzyme tests, and pulmonary imaging examination, with close monitoring of the patient's pulmonary condition. If drug-induced lung injury is suspected, the medication should be discontinued immediately, and appropriate treatment should be initiated promptly. [ABSTRACT FROM AUTHOR]

Background Encouraging antitumor activity of nab-paclitaxel plus S-1 (AS) has been shown in several small-scale studies. This study compared the efficacy and safety of AS versus standard-of-care nab-paclitaxel plus gemcitabine (AG) as a first-line treatment for advanced pancreatic cancer (PC). Methods In this multicenter, randomized, phase II trial, eligible patients with unresectable, locally advanced, or metastatic PC were recruited and randomly assigned (1:1) to receive AS (nab-paclitaxel 125 mg/m2 on days 1 and 8; S-1 twice daily on days 1 through 14) or AG (nab-paclitaxel 125 mg/m2 on days 1 and 8; gemcitabine 1000 mg/m2 on days 1 and 8) for 6 cycles. The primary endpoint was progression-free survival (PFS). Results Between July 16, 2019, and September 9, 2022, 62 patients (AS, n  = 32; AG, n  = 30) were treated and evaluated. With a median follow-up of 8.36 months at preplanned interim analysis (data cutoff, March 24, 2023), the median PFS (8.48 vs 4.47 months; hazard ratio [HR], 0.402; P  = .002) and overall survival (OS; 13.73 vs 9.59 months; HR, 0.226; P  < .001) in the AS group were significantly longer compared to the AG group. More patients had objective response in the AS group than AG group (37.50% vs 6.67%; P  = .005). The most common grade 3-4 adverse events were neutropenia and leucopenia in both groups, and gamma glutamyl transferase increase was observed only in the AG group. Conclusion The first-line AS regimen significantly extended both PFS and OS of Chinese patients with advanced PC when compared with the AG regimen, with a comparable safety profile. (ClinicalTrials.gov Identifier: NCT03636308). [ABSTRACT FROM AUTHOR]

Simple Summary: Adjuvant chemotherapy (AC) with S1 is beneficial for pancreatic cancer, but the completion rate of S1 remains at 70%. Additionally, there are no useful indicators for achieving completion of S1. Therefore, we have assumed that studying the C-reactive protein-to-albumin ratio as an indicator based on nutritional status may be useful in predicting this. When this indicator proves effective, we believe that more cases can complete the treatment by improving nutrition or adjusting the dosage before starting AC. Adjuvant chemotherapy (AC) with S-1 after radical surgery for resectable pancreatic cancer (PC) has shown a significant survival advantage over surgery alone. Consequently, ensuring that patients receive a consistent, uninterrupted S-1 regimen is of paramount importance. This study aimed to investigate whether the C-reactive protein-to-albumin ratio (CAR) could predict S-1 AC completion in PC patients without dropout due to adverse events (AEs). We retrospectively enrolled 95 patients who underwent radical pancreatectomy and S-1 AC for PC between January 2010 and December 2022. A statistical analysis was conducted to explore the correlation of predictive markers with S-1 completion, defined as continuous oral administration for 6 months. Among the 95 enrolled patients, 66 (69.5%) completed S-1, and 29 (30.5%) failed. Receiver operating characteristic curve analysis revealed 0.05 as the optimal CAR threshold to predict S-1 completion. Univariate and multivariate analyses further validated that a CAR ≥ 0.05 was independently correlated with S-1 completion (p < 0.001 and p = 0.006, respectively). Furthermore, a significant association was established between a higher CAR at initiation of oral administration and acceptable recurrence-free and overall survival (p = 0.003 and p < 0.001, respectively). CAR ≥ 0.05 serves as a predictive marker for difficulty in completing S-1 treatment as AC for PC due to AEs. [ABSTRACT FROM AUTHOR]

Simple Summary: Cervical cancer is the fourth most common cancer in the world and the fourth leading cause of cancer death in women. In 2020, there were 604,000 new cases and 342,000 deaths from cervical cancer worldwide. Among these, non-squamous cell carcinoma accounts for about 20% of all cervical cancers and is increasing. It has long been known that non-squamous cervical cancer has a poorer prognosis than squamous cervical cancer. Reasons for this include relatively early lymph node metastasis and low sensitivity to radiotherapy. Therefore, chemotherapy is more likely to improve prognosis than radiotherapy. However, there are few studies on adenocarcinoma and a high level of evidence is not yet available. We have previously reported the efficacy of SOX (S-1+oxaliplatin) therapy for cervical adenocarcinoma in a pilot study. We report on a phase II trial of SOX therapy to evaluate its efficacy and safety. Recurrent non-squamous cell carcinoma (non-SCC) of the uterine cervix is resistant to treatment and has a poor prognosis. The efficacy and safety of S-1/oxaliplatin (SOX) therapy in patients with recurrent non-SCC was examined in a phase II study. Fifteen patients were enrolled between August 2013 and March 2023. S-1 was administered orally at a daily dose of 80–120 mg for 14 days, and oxaliplatin was administered intravenously at a dose of 100 mg/m2 on day 1. Each treatment cycle lasted 21 days. The anti-tumor effects, adverse events, progression-free survival (PFS), and overall survival (OS) were investigated. The median patient age was 54 (41–74) years. The anti-tumor effect was rated as a partial response in five patients, stable disease in four, and progressive disease in 6. The overall response rate was 33% and the disease control rate was 60%. Regarding hematologic toxicities of grade 3 or more severity, leukopenia, neutropenia, anemia, and thrombocytopenia occurred in 26.6–40.0%. None of the patients discontinued the treatment because of adverse events. The median PFS and OS were 6 months (95% confidence interval [CI]: 2–11 months) and 22 months (95% CI: 11–23 months), respectively. No treatment-related deaths occurred. These results suggest that SOX therapy is useful for the treatment of recurrent non-SCC with promising anti-tumor effects and minimal adverse events. [ABSTRACT FROM AUTHOR]

The aim of the study was to observe the safety and efficacy of anlotinib (ANL) alone or combined with S-1 in the first-line treatment of advanced hepatocellular carcinoma (HCC). Fifty-four patients with untreated advanced HCC who could not be resected were randomly divided into the ANL group (n = 27) and ANL+S-1 group (n = 27). The ANL group was given 10 mg ANL orally once a day for 14 consecutive days, stopped for 1 week, and repeated every 21 days. The ANL+S-1 group was given 10 mg ANL once a day orally and 40 mg S-1 twice a day orally for 14 consecutive days, stopped for 1 week, repeated every 21 days. All patients were treated until the disease progressed or toxicity became unacceptable. For patients who could not tolerate adverse reactions, the ANL dose should be reduced to 8 mg per day. CT or MRI was reviewed every 6 weeks to evaluate the efficacy. A total of 44 patients were included in the results analysis, including 22 patients in the ANL group and 22 patients in the ANL+S-1 group. In the ANL group, the objective response rate (ORR) was 4.5% (1/22), the disease control rate (DCR) was 77.3% (17/22), the median progression-free survival (PFS) was 4.2 months (95% CI: 3.6–6.0) and the median overall survival (mOS) was 7.0 months (95% CI: 6.3–9.0). In the ANL+S-1 group, the ORR was 18.2% (4/22), the DCR was 59.1% (13/22), the median PFS was 4.0 months (95% CI: 3.6–5.4) and the mOS was 6.0 months (95% CI: 5.5–7.4). There was no significant difference in ORR (p = 0.345) or DCR (p = 0.195) between the two groups. Adverse reactions were mainly hypertension, anorexia, fatigue, liver transaminase heightened and hand and foot skin reaction. ANL monotherapy was effective in the treatment of advanced HCC, and adverse reactions have been able to tolerated. [ABSTRACT FROM AUTHOR]

Background Systemic chemotherapy is the primary treatment in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). More effective treatment options are highly awaited. The aim of this study was to evaluate the toxicity and feasibility of gemcitabine/nab-paclitaxel/S-1 (GAS) chemotherapy on a 21-day cycle in patients with locally advanced or metastatic PDAC, determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of S-1 in this regimen, and explore preliminary efficacy. Methods Eligible patients with locally advanced or metastatic PDAC received GAS chemotherapy on a 21-day cycle. Fixed-dose nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) were given intravenously on days 1 and 8. Different doses of S-1 were given orally twice daily from day 1 to day 14 in a 3+3 dose escalation design. According to patients' body surface area, the dose-escalation design was as follows: patients with a body surface area of 1.25-1.5 m2 received S-1 40 mg/day initially and the dose was increased to 60 mg or 80 mg. Patients with a body surface area of more than 1.5 m2 received S-1 60 mg/day initially and the dose was increased to 80 mg or 100 mg. The primary endpoints were to evaluate the toxicity and determine the DLT and MTD of S-1. The secondary endpoint was to evaluate efficacy, including best objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). adverse events (AEs) were evaluated according to the NCI-CTCAE 5.0. Tumor response was assessed using the RECIST 1.1. Results A total of 21 eligible patients were included. Due to the infrequence of patients with a body surface area of 1.25-1.5 m2, only 2 patients were included in cohort of S-1 40 mg. The dose-escalation for patients in this group failed to be enrolled completely. For patients with a body surface area of more than 1.5 m2, 3 DLTs in 7 patients were detected at cohort of S-1 100 mg (grade 3 thrombocytopenia with hemorrhage, grade 3 rash, and grade 3 mucositis/stomatitis). S-1 80 mg/day (body surface area: >1.5 m2) was considered to be the MTD in GAS chemotherapy on a 21-day cycle. No grade 4 AEs or treatment-related deaths were observed. The most commonly occurring hematologic AE of any grade was anemia (38.1%). The most frequent nonhematologic AEs of any grade were peripheral neuropathy (38.1%), dyspepsia (23.8%), constipation (23.8%), and alopecia (23.8%). Response assessment showed that the best ORR was 36.8% (7 of 19 patients) and the DCR was 94.7% (18 of 19 patients). The median PFS was 5.3 (95% CI, 4.6 to 6.0) months and the median OS was 10.3 (95% CI, 8.1 to 12.5) months. Conclusion GAS chemotherapy (21-day cycle) with nab-paclitaxel 125 mg/m2, gemcitabine 1000 mg/m2, and S-1 80 mg/day (body surface area: >1.5 m2) was found to have acceptable toxicity and significant clinical control in patients with locally advanced or metastatic PDAC. We conclude that further trials with this combination are warranted. (Trial Identifier: ChiCTR1900027833 [chictr.org]). [ABSTRACT FROM AUTHOR]

Simple Summary: There is no clear preference between S-1 and capecitabine in combination with platinum agent as first-line therapy for patients with HER2-negative unresectable advanced or recurrent gastric cancer (GC) with measurable disease. Although a distinguishing use of S-1 versus capecitabine based on histological classification has been studied, the present integrated analysis, using 162 individual participant data of GC patients with measurable disease, is the first to show that S-1 plus cisplatin (SP) achieves deeper tumor shrinkage than capecitabine plus cisplatin (XP), leading a longer overall survival although no differences in response rate or progression-free survival in differentiated GC. On the other hand, in undifferentiated GC, SP consistently showed better clinical results than XP. These findings thus have implications for the choice of oral fluoropyrimidine in the era of first line therapy in combination with oxaliplatin and immune checkpoint inhibitor. It has been suggested that the therapeutic efficacy of S-1 + cisplatin (SP) and capecitabine + cisplatin (XP) may differ depending on the histology of the tumor, but no clear evidence exists. Individual participant data were obtained from three randomized phase II trials in which such patients received either SP (S-1 [40–60 mg twice daily for 21 days] plus cisplatin [60 mg/m2 on day 8], every 5 weeks) or XP (capecitabine [1000 mg/m2 twice daily for 14 days] plus cisplatin [80 mg/m2 on day 1], every 3 weeks). A total of 162 patients were included, with 79 patients in the SP arm and 83 patients in the XP arm. Although there was also no difference between arms in ORR according to histological classification, differentiated tumors showed a significantly better OS (but not PFS) for SP versus XP that was associated with a deeper tumor shrinkage. Undifferentiated tumors showed a consistently better OS, and PFS for SP versus XP, likely because cases without tumor shrinkage tended to be fewer for SP. Our data thus showed that SP was superior to XP in this setting, but there were qualitative differences in therapeutic efficacy dependent on tumor histology. [ABSTRACT FROM AUTHOR]

This phase 1b trial evaluated the toxicity and efficacy of S-1, irinotecan, and oxaliplatin combination therapy (S-IROX) as first-line chemotherapy in patients with advanced pancreatic cancer (APC). Patients aged 20–75 years with APC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible to receive escalating doses of S-1 (60 or 80 mg m2·day) on days 1–7, fixed doses of oxaliplatin (85 mg/m2) biweekly, and escalating doses of irinotecan (150, 165, or 180 mg/m2) once every 2 weeks. In the dose-escalation cohort, a 3 + 3 design was used to determine the maximum-tolerated dose (MTD) and explore the recommended dose (RD). A dose-expansion cohort was added to further evaluate the safety and efficacy of the combination. This trial was registered at UMIN-CTR (UMIN000012054). Approximately 47 patients were enrolled, of whom 45 were eligible for the analysis. The MTD was not determined, but the RD was determined to be dose level 1 based on a review of data from each level. Among the 45 patients, the ORR was 51.1% [95% confidence interval (CI), 35.8–66.3%]. The median progression-free survival and median overall survival was 6.9 months (95% CI, 5.1–8.8 months) and 15.8 months (95% CI, 9.8–20.8 months), respectively. Common adverse events included neutropenia, elevated liver enzyme levels, diarrhoea, and nausea. The S-IROX regimen showed promising efficacy with manageable toxicities in Japanese patients with APC. A randomised phase 2/3 trial comparing S-IROX, mFOLFIRINOX, and gemcitabine plus nab-paclitaxel is currently ongoing (jRCTs031190009). • Phase 1b trial of S-1, irinotecan, and oxaliplatin in pancreatic cancer. • The RD was S-1 80 mg/m2, irinotecan 150 mg/m2, and oxaliplatin 85 mg/m2. • The ORR was 51.1%, and PFS and OS were better than those of the historical FOLFIRINOX. [ABSTRACT FROM AUTHOR]

Summary: Purpose. This study aimed to evaluate the effectiveness and safety of gemcitabine (GEM) plus nab-paclitaxel (GnP) in patients aged ≥ 75 years with advanced pancreatic cancer and compare it with monotherapy (GEM or S-1). Methods. We retrospectively reviewed the data of consecutive patients with advanced pancreatic cancer aged ≥ 75 years who received either GnP or monotherapy (GEM or S-1) between January 2014 and May 2020. The primary efficacy outcome was overall survival (OS). Results. A total of 96 patients were included in this study; 51 were treated with GnP and 45 with monotherapy (31 with GEM and 14 with S-1). The median OS and progression-free survival were 10.8 and 6.7 months in the GnP group and 10.7 and 4.3 months in the monotherapy group, respectively. The treatment effect on OS was consistently favorable in the GnP group across most subgroups, particularly in patients with locally advanced cancer, modified Glasgow prognostic score of 0 or 1, and neutrophil/lymphocyte ratio < 3.1. The disease control rates were 76% and 48% in the GnP and monotherapy groups, respectively, and grade 3 or 4 neutropenia occurred in 23 (45%) and 11 (24%) patients of the GnP and monotherapy groups, respectively. Conclusions. This study demonstrated that GnP was not superior to monotherapy with regard to OS. However, multivariate analysis showed that GnP treatment positively affected the OS and could be considered as a treatment option, even for elderly patients. [ABSTRACT FROM AUTHOR]

Background: Combination chemotherapy is used to treat advanced thymic carcinoma; however, the effects are insufficient. Methods: Previously untreated patients with unresectable locally advanced thymic carcinoma received two cycles of 80 mg/m2/day S‐1 orally on days 1–14 plus 60 mg/m2/day cisplatin intravenously on day 1, and concurrent radiotherapy (60 Gy). Results: Three patients were enrolled into the study. Toxicity and survival were assessable in all patients, but the treatment response was only assessable in one patient. The study was terminated because of poor case recruitment. The patients' characteristics were as follows: male/female = 2/1; PS 0/1 = 2/1; median age (range) = 59 (55–72); and stage III/IV = 2/1. The patient in which the treatment response was assessed exhibited SD (response rate: 0%). In both nonevaluable cases, the second course of chemotherapy was judged to be post‐protocol treatment because it was delayed by ≥14 days, but a CR and PR were achieved after the end of the study, respectively. G4 leukopenia/neutropenia and G3 febrile neutropenia occurred in one patient each (33%). The median time to tumor progression was 17.6 months, and the 1‐, 2‐, 3‐, and 4‐year survival rates were 67, 33, 33, and 33%, respectively. The median overall survival time was not reached, and the 1‐, 2‐, 3‐, and 4‐year survival rates were 100, 67, 67, and 67%, respectively. Conclusions: Although it was difficult to recruit patients, there was a long‐term survivor >4 years who appeared to have achieved a CR, indicating that such chemoradiotherapy may be effective against locally advanced thymic carcinoma. [ABSTRACT FROM AUTHOR]

Background: Although docetaxel plus S-1 adjuvant chemotherapy after gastrectomy with D2 lymphadenectomy has been a standard of treatment for stage III gastric cancer, there is no established chemotherapy for patients with recurrence during or within six months after the completion of adjuvant docetaxel plus S-1 therapy.Methods: The OGSG 1901 trial is a prospective, open-label, multicenter, phase II trial evaluating ramucirumab plus irinotecan for gastric cancer patients with early relapse after adjuvant docetaxel plus S-1 therapy. The key eligibility criteria were: 1) histologically confirmed gastric adenocarcinoma 2) patients who were on docetaxel plus S-1 adjuvant chemotherapy after the confirmation of pathological stage III, 3) patients with early relapse, i.e., recurrence during or within 6 months after the completion of docetaxel plus S-1 therapy, and 4) patient with Eastern Cooperative Oncology Group performance status of 0-1. Irinotecan (150 mg/m2, day 1) and ramucirumab (8 mg/kg, day 1) will be administered every 2 weeks. The primary endpoint is overall survival, and the secondary endpoints are overall response rate, progression-free survival, and safety. The number of patients has been set at 40 based on the threshold and expected median survival times of 7 and 11 months, respectively, with a one-sided alpha error of 0.05 and power of 0.80. The enrollment and follow-up periods are 2 and 1.5 years, respectively.Discussion: The results of this trial will indicate whether the ramucirumab with irinotecan regimen has the potential to be a recommended treatment regimen for patients with recurrence gastric cancer during or within 6 months after the completion of adjuvant docetaxel plus S-1 therapy.Trial Registration: This study was registered in the Japan Registry of Clinical Trials ( jRCTs05119071 , October 6, 2019). [ABSTRACT FROM AUTHOR]

The mainstream first-line chemotherapy for advanced/recurrent gastric cancer (ARGC) is combination therapy including platinum-based agents. With the progressive aging of the society, the incidence of gastric cancer in elderly patients is increasing. However, elderly patients cannot tolerate these agents because of renal dysfunction or low quality of life. The KSCC1701 study explored the efficacy and safety of S-1 + ramucirumab in elderly patients with ARGC. Chemotherapy-naive patients aged ≥70 years with ARGC were eligible. Patients received S-1 (40–60 mg twice daily for 4 weeks in 6-week cycles) and ramucirumab (8 mg/kg every 2 weeks) until disease progression. The primary end-point was the 1-year overall survival (OS) rate. The anticipated lower threshold of 1-year survival was set at 40% in light of previous S-1–based regimens. The secondary end-points included progression-free survival (PFS), OS, the overall response rate (ORR) and safety. Between September 2017 and November 2019, 48 patients (34 men and 14 women) were enrolled in this study. The median patient age was 77.5 years, and all patients had a performance status of 0 (n = 20) or 1 (n = 28). The 1-year OS rate was 65.2%, which met the primary end-point. The median survival time and median PFS were 16.4 and 5.8 months, respectively. The ORR was 41.9%. The most frequent grade 3/4 (≥15%) adverse events were neutropenia, anorexia and anaemia. Considering these findings, S-1 + ramucirumab appears to be an excellent treatment option for elderly patients with ARGC. (250 words). This trial has been registered with the Japan Registry of Clinical Trials Registry under the number jRCTs071180066. • Elderly ARGC patients with good performance status were enrolled. • Explored the efficacy and safety of S-1 + ramucirumab, achieved good OS. • PFS and ORR were also sufficient results. • Frequent grade 3/4 (≥15%) adverse events were neutropenia, anorexia and anaemia. [ABSTRACT FROM AUTHOR]

S-1 is an oral fluoropyrimidine that is increasingly used in Western countries for the treatment of metastatic colorectal cancer (mCRC). We conducted a non-inferiority meta-analysis on the efficacy of S-1-based therapy versus 5-fluorouracil (5-FU)- or capecitabine-based therapy in the treatment of patients with mCRC. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Opengrey were searched for randomised clinical trials until May 2021. Data were extracted for progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and adverse events. Pooled effect estimates, stratified by treatment line, with corresponding 99% confidence intervals (CI) were presented. For PFS, a pre-defined non-inferiority margin (ΔNI) of 1.25 was selected. Ten studies (n = 2117) were included, of which six studies reported PFS and OS data and 10 studies reported ORR data. S-1-based therapy was shown to be non-inferior to 5-FU/capecitabine-based therapy in terms of PFS (HR total 0.95, 99% CI 0.83–1.08) with its CI upper limit well below ΔNI, and at least as efficacious in terms of OS (HR total 0.93, 99% CI 0.81–1.07), and ORR (RR total 1.06, 99% CI 0.90–1.24). S-1-based therapy is non-inferior to 5-FU/capecitabine-based therapy in the treatment of mCRC regarding PFS and at least as efficacious as 5-FU/capecitabine-based therapy in terms of ORR and OS. These data support the use of S-1 in mCRC patients who are intolerant to 5-FU/capecitabine-based treatment. • In Asian countries, S-1 is standard of care for patients with unresectable mCRC. • S-1 has lower incidence of hand–foot syndrome and cardiac toxicities in Western mCRC. • S-1-based therapy is non-inferior to 5-FU/capecitabine-based therapy in mCRC. • Replacement of 5-FU or capecitabine by S-1 does not compromise efficacy in mCRC. [ABSTRACT FROM AUTHOR]

The prognosis of stage III gastric cancer (GC) is not satisfying and the specific chemotherapy regimens for GC of stage IIIC based on the 8th edition of the UICC/AJCC TNM staging system are still inconclusive. Peritoneal recurrence is the common and severe relapse pattern. Nanoparticle albumin-bound paclitaxel (Nab-PTX) is safer and more effective than PTX in the peritoneal metastasis. Clinical trial has demonstrated the safety and efficacy of sintilimab in GC. A combination of Nab-PTX, S-1 and sintilimab could be a promising triplet regimen as adjuvant therapy for GC. The aim of this article is to describe the design of this prospective Dragon-VII trial, conducted to evaluate the safety and efficacy of the combination of Nab-PTX, S-1 and sintilimab. Clinical trial registration: NCT04781413. [ABSTRACT FROM AUTHOR]

The efficacy of modified FOLFIRINOX (mFOLFIRINOX) as a second-line chemotherapy treatment for metastatic pancreatic adenocarcinoma (mPAC), remains unclear. This multi-center randomised phase III trial aimed to elucidate the efficacy of mFOLFIRINOX as a second-line chemotherapy treatment for mPAC patients with good performance status. Eighty mPAC patients (age, 19–75 years) refractory to first-line gemcitabine-based chemotherapy were randomly selected to receive mFOLFIRINOX or S-1. mFOLFIRINOX comprised oxaliplatin (65 mg/m2), irinotecan (135 mg/m2), and leucovorin (400 mg/m2) on day 1 and continuous 5-FU infusion (1000 mg/m2) over 24 h on days 1–2 every 2 weeks. S-1 comprised body surface area-dependent oral S-1, divided into two doses per day on days 1–28 every 6 weeks. Overall survival was the primary endpoint. The objective response and disease control rates were higher in the mFOLFIRINOX than in the S-1 group (15% versus 2%; p =.04 and 67% versus 37%; p =.007). The median progression-free survival rates were 5.2 and 2.2 months in the mFOLFIRINOX and S-1 groups, respectively (adjusted hazard ratio [HR]:.4; 95% confidence interval [CI]:.2-.6; p <.001). The median overall survival rates were 9.2 and 4.9 months in the mFOLFIRINOX and S-1 groups, respectively (adjusted HR:.4; 95% CI:.2–.7; p =.002). Grade 3-4 adverse events occurred in 56% and 17% of the patients in the mFOLFIRINOX and S-1 groups, respectively (p <.001). Administration of mFOLFIRINOX as a second-line chemotherapy treatment for mPAC patients refractory to gemcitabine-based chemotherapy resulted in increased survival rates than S-1 treatment alone. • mPAC patients with good PS refractory to gemcitabine-based therapy were enrolled. • Compared with S-1, mFOLFIRINOX significantly prolonged OS and PFS. • ORR and DCR were higher in the mFOLFIRINOX group than in the S-1 group. • Grade 3–4 toxicities were more common in the mFOLFIRINOX group than in the S-1 group. [ABSTRACT FROM AUTHOR]

Introduction: The usefulness of adjuvant chemotherapy in biliary tract cancer (BTC) is poorly reported. This study aimed to evaluate the effectiveness and safety of adjuvant gemcitabine plus S-1 (GS) chemotherapy after curative surgical resection for BTC. Methods: 225 BTC patients who underwent surgical resection between January 2006 and May 2019 were enrolled in this study. Twenty-seven patients received adjuvant chemotherapy with GS (GS group), whereas 67 patients underwent surgery alone (S group). Twenty-three matching pairs were derived through propensity score (PS) matching analysis. Patients received 12 cycles of adjuvant chemotherapy (70 mg/m2 oral S-1 for 7 consecutive days plus intravenous gemcitabine 1,000 mg/m2 on day 7). The primary end point was recurrence-free survival (RFS). The secondary end points were the 1-, 2-, and 3-year RFS and overall survival (OS) rates, tolerability, and frequency of grade 3/4 toxicity. Results: The completion rate was 81.5%; no treatment-related deaths were observed. Grade 3/4 adverse events were seen in 40.7% of the patients. RFS (3-year RFS rate: 59.3% vs. 39.1%, p = 0.049) and OS (3-year OS rate: 71.7% vs. 53.4%, p = 0.008) were significantly better in the GS group than in the S group among PS-matched pairs. Discussion/Conclusion: GS chemotherapy after curative surgery was well tolerated, showed better clinical benefit in the adjuvant setting, and can effectively reduce BTC recurrence. [ABSTRACT FROM AUTHOR]

This multicenter phase I/IIa study aimed to determine the recommended phase II dose (RP2D) and evaluate the safety and preliminary efficacy of liposomal irinotecan (nal-IRI), oxaliplatin, and S-1 (NASOX) as first-line treatment for advanced pancreatic adenocarcinoma. Patients with locally advanced or metastatic pancreatic adenocarcinoma without prior systemic treatment for advanced disease, aged ≥ 19 years, with measurable disease, and Eastern Cooperative Oncology Group performance status of 0–1 were eligible. The primary endpoints were to determine the dose-limiting toxicity (DLT) in the phase I cohort and overall response rate (ORR) in the phase IIa cohort. The intention-to-treat (ITT) analysis included patients who received the RP2D. In phase I, seven patients were screened, and six were assessed for DLT. None experienced DLT during the first cycle. The RP2D was determined as nal-IRI 50 mg/m2 and oxaliplatin 60 mg/m2 on day 1, S-1 40 mg/m2 twice daily on days 1–7 every 14 days. For the ITT (N = 41; 7, and 34 from phases I and IIa, respectively), the most common grade 3–4 treatment-emergent adverse events were neutropenia (31.7 %), enterocolitis (9.8 %), anorexia (7.3 %), and diarrhea (2.4 %). The ORR was 58.5 % (1 complete, and 23 partial responses). Two underwent conversion surgery; both achieved R0 resection. With median follow-up of 17.5 months, median progression-free survival was 6.5 months (95 % confidence interval [CI], 5.0–8.1) and median overall survival was 11.4 months (95 % CI, 9.8–15.5). NASOX exhibited a manageable safety profile and encouraging efficacy outcomes consistent with NALIRIFOX, showing potential to replace infusional 5-fluorouracil with oral S-1 in the triplet regimen. • In this Ph I/IIa trial, patients with advanced PDAC received 1 L NASOX every 2 weeks. • RP2D: nal-IRI 50 mg/m2, oxaliplatin 60 mg/m2 on D1, S-1 40 mg/m2 BID on D1–7. • ORR was 58.5 %, median PFS was 6.5 months, and median OS was 11.4 months. • Safety profiles were manageable. • NASOX may improve patient convenience while showing efficacy comparable to NALIRIFOX. [ABSTRACT FROM AUTHOR]

Introduction: S-1, a compounding agent of tegafur, gimeracil, and oteracil potassium, is one of the most effective chemotherapeutic agents for colorectal cancer. In this case, following S-1 administration, we observed predominant elevation of serum triglyceride. Case report: A 49-year-old man with stage IV transverse colon adenocarcinoma received S-1 + irinotecan + bevacizumab. At the end of the S-1 administration period in every course, his serum triglyceride level was found to be elevated. Finally, it reached grade 4, without any symptoms of acute pancreatitis in the fifth course, and fenofibrate 80 mg once a day was administered. Management & outcome: Interestingly, the elevation spontaneously normalized without any pharmacotherapy 14 days after S-1 withdrawal, and this elevation did not occur when S-1 was not administered. Further, fenofibrate administration attenuated the hypertriglyceridemia to grades 1-3, with no complications. Discussion: S-1 administration induced hypertriglyceridemia owing to the elevated serum triglyceride; however, a contrasting result was observed in the S-1 withdrawal period and during the S-1-cessation cycle. Since dietary intake was poorer during the S-1 administration period, it is considered that S-1 might have disturbed lipid metabolism. Further, we know that capecitabine, which is a prodrug of fluorouracil, also induces hypertriglyceridemia. As the end product of these medicines is fluorouracil, the presence of fluorouracil or its metabolizing enzymes, the genetic background of the patient might have affected the results. We have to be aware of the risk of asymptomatic and temporal occurrence of hypertriglyceridemia by S-1 administration for the early detection with appropriate pre-emptive treatment. [ABSTRACT FROM AUTHOR]

Purpose: The study aimed to investigate the potential benefit of more than 4 courses of S1 adjuvant chemotherapy for patients with pancreatic ductal adenocarcinoma (PDAC) after surgery.Method: Data were retrospectively collected from consecutive patients who underwent S-1 adjuvant chemotherapy following curative pancreatectomy between January 2016 and December 2018. Four-courses and > 4 courses cohorts were compared for overall survival (OS) as a primary outcome, and relapse-free survival (RFS) and adverse event incidence as secondary outcomes.Results: Four-courses and > 4 courses cohorts comprised 99 patients and 64 ones, respectively. TNM stage (stage II vs. I: HR, 2.125; 95% CI, 1.164-4.213; P = 0.015), duration of S-1 administration (4 vs. > 4 courses: HR, 3.113; 95% CI, 1.531-6.327; P = 0.002) and tumor grade (G3 vs. G1/2: HR, 3.887; 95% CI, 1.922-7.861; P < 0.001) were independent prognostic factors. Under the condition of patients' survival time beyond 8 months, the OS of patients in > 4 courses cohort was significantly prolonged compared with that of 4 courses cohort (4 vs. > 4 courses: HR, 2.284; 95% CI, 1.197-4.358; P = 0.012), especially for patients in TNM stageII (4 vs. > 4 courses: HR, 2.906; 95% CI, 1.275-6.623; P = 0.011).RFS and adverse events incidence did not signifcantly difer between both cohorts.Conclusion: Prolonged duration of S-1 intake is beneficial to prognosis of patients with PDAC resection. [ABSTRACT FROM AUTHOR]

Drug‐drug interaction of fluorinated pyrimidine anticancer agents with phenytoin is well known, but interaction with phenobarbital is limited. We describe a case showing increases in plasma phenobarbital as well as phenytoin concentrations during preoperative S‐1 (tegafur/gimeracil/oteracil) and radiation therapy for rectal cancer. [ABSTRACT FROM AUTHOR]