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Background: Adjuvant chemotherapy is the conventional treatment for stage II and III gastric cancer(GC). Postoperative doublet chemotherapy has consistently shown improved survival outcomes in advanced-stage GC patients compared to single-agent regimens. Triplet regimens have shown significant survival benefits in the perioperative settings. This retrospective study evaluated the efficacy and safety of paclitaxel/S-1/oxaliplatin (PSOX) compared to S-1/oxaliplatin (SOX) as postoperative adjuvant chemotherapy in stage II-III GC patients following D2 gastrectomy. Methods: A retrospective review was conducted on patients with histologically confirmed stage II-III gastric cancer who underwent D2 gastrectomy at Jiangsu Cancer Hospital, categorizing them into two groups. A total of 75 patients were included in PSOX group and 81 patients in the SOX group between April 2018 and August 2021. Patients in PSOX group received paclitaxel (120 mg/m2), oxaliplatin (100 mg/m2) and S-1 (80 − 60 mg/d) per cycle, while those patients in SOX group were administrated oxaliplatin (130 mg/m2) and S-1 (80–120 mg/d) per cycle. Patients from both groups were matched in a 1:1 ratio using propensity scores to assess differences in disease-free survival (DFS) and safety. Results: The 3-year DFS rate was 78.2% for the PSOX group and 74.0% for the SOX group (P = 0.355), with a hazard ratio for peritoneal relapse of 0.287 (95% CI, 0.090–0.915; P = 0.035). Subgroup analysis indicated that stage IIIC GC patients in the PSOX group had a higher DFS rate than those in the SOX group(P = 0.032). Grade 3 or 4 adverse events, as per the National Cancer Institute Common Toxicity Criteria, such as leucopenia (10.6% vs. 4.5%), neutropenia (10.6% vs. 9.1%), nausea/vomiting (4.5% vs. 3.0%), and diarrhea (4.5% vs. 3.0%) were relatively common in the PSOX group compared to the SOX group, with no statistically significant differences between the two groups. Conclusion: Our findings suggested that adjuvant PSOX chemotherapy offers superior survival benefits compared to the SOX regimen in patients with staged IIIC GC after D2 gastrectomy. The incidence of adverse events with PSOX chemotherapy was comparable to that of SOX chemotherapy. [ABSTRACT FROM AUTHOR]

Objective: S-1, an oral multicomponent capsule containing tegafur, gimeracil, and potassium oxonate, has demonstrated efficacy in various tumor types. This study aimed to assess the pharmacokinetics, bioequivalence (BE), and safety of a newly developed generic S-1 capsule compared to the original brand-name formulation in Chinese cancer patients under fasting and fed conditions. Methods: A multicenter, randomized, open-label, single-dose, double-cycle crossover study was conducted in Chinese cancer patients. The study involved 120 subjects, with 60 assigned to the fasting group and another 60 to the fed group. In each study cycle, subjects were randomly assigned toreceive either the reference or test S-1 capsule at a 7-day interval. Blood samples were collected for analysis within 48 h after ingestion. The plasma concentrations of tegafur, 5-fluorouracil, gimeracil, and potassium oxonate were determined by liquid chromatography–tandem mass spectrometry (LC-MS/MS). The main pharmacokinetic (PK) parameters were calculated using the non-compartmental approach. BE was assessed through geometric mean ratios (GMRs) between the two formulations and their respective 90% confidence intervals (CIs). The safety of the two formulations was also evaluated. Results: The pharmacokinetics of the two formulations were similar under both fasting and fed conditions. The 90% CIs of the GMRs for the maximum observed serum concentration (Cmax), AUC0-t, and AUC0- ∞ ratios were observed to lie within the BE acceptance range of 80%–125%. Both formulations of the S-1 capsule exhibited similar adverse events (AEs), primarily including decreased white blood cell count and hypertension. These AEs were generally mild and transient. The safety profiles of the two formulations were found to be good and comparable, with no serious adverse events (SAEs) reported. Conclusion: The newly developed generic S-1 and reference formulations exhibit comparable PK in Chinese cancer patients in the fasting and fed state. The formulations of S-1 showed good tolerability and a similar safety profile. Clinical Trial Registration: http://www.chinadrugtrials.org.cn/index.html, identifier CTR20171562. [ABSTRACT FROM AUTHOR]

Background: S-1 monotherapy had previously been widely used as a second-line treatment for pancreatic cancer (PC) after gemcitabine-based chemotherapy mainly in Japan. Based on the results of the NAPOLI-1 trial, the recommended second-line therapy is now liposomal irinotecan plus fluorouracil/folinic acid (nal-IRI + 5-FU/LV). However, there have been no studies comparing nal-IRI + 5-FU/LV therapy with S-1 monotherapy. Methods: The main objective of this study was to compare overall survival (OS) in patients treated with nal-IRI + 5-FU/LV and those treated with S-1 monotherapy as second-line treatments, using the inverse probability of treatment weighting (IPTW) method. This study was conducted in 31 institutions participating in Japan Oncology Network in Hepatobiliary and Pancreas. To minimize potential biases due to the retrospective design, IPTW analysis was performed with multiple imputation, and imputed IPTW-adjusted hazard ratios and corresponding 95% confidence intervals (CIs) were estimated using a Cox proportional hazards model and combined into pooled estimates. Results: A total of 463 metastatic PC patients were enrolled in this study (257 in the S-1 monotherapy group and 206 in the nal-IRI + 5-FU/LV group). The median OS was 7.50 months (95% CI 4.18–12.69 months) in the nal-IRI + 5-FU/LV group and 5.72 months (95% CI 2.76–10.79 months) in the S-1 monotherapy group. In the IPTW-adjusted Cox proportional hazards model, nal-IRI + 5-FU/LV was associated with a significant OS benefit (pooled IPTW-adjusted hazard ratio, 0.779; 95% CI 0.399—0.941; p = 0.025). Conclusion: These findings support the use of nal-IRI + 5-FU/LV as standard second-line treatment for PC patients after gemcitabine-based chemotherapy. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to compare outcomes and adverse events between three-dimensional conformal radiation therapy (3D-CRT) and intensity-modulated radiation therapy (IMRT) in patients undergoing long-course neoadjuvant radiation therapy (NA-RT) for locally advanced rectal adenocarcinoma (LARC). Methods: We retrospectively analyzed a total of 47 consecutive patients who received NA-RT for LARC between January 2011 and September 2022. Seven and 40 patients were diagnosed with clinical stages II and III, respectively. The prescribed dose per fraction was 1.8 Gy for total doses of 45 or 50.4 Gy. Seventeen and 30 patients received 3D-CRT and IMRT, respectively. NA-RT was delivered with concurrent chemotherapy of oral administration of S-1. Results: Planned NA-RT was completed without any treatment interruption in 43 of the 47 patients. Two patients experienced treatment interruption, and two patients discontinued due to grade ≥ 3 toxicities. No significant differences were observed between patients receiving 3D-CRT and IMRT in local control, progression-free survival, and overall survival (P = 0.488, 0.259, and 0.636, respectively). Patients receiving IMRT showed significantly fewer non-hematological grade ≥ 2 acute toxicities than those receiving 3D-CRT (33.3% vs. 70.6%, P = 0.018). In addition, patients who received IMRT tended to have less intestinal toxicity of grade ≥ 2 than those who received 3D-CRT (P = 0.057). Conclusion: IMRT significantly reduced grade ≥ 2 acute toxicities without compromising oncologic outcomes compared to 3D-CRT. Therefore, IMRT may be considered as a current standard treatment in the total neoadjuvant therapy era. [ABSTRACT FROM AUTHOR]

Background: Metastatic colorectal cancer (mCRC) remains a significant clinical challenge, particularly for patients who have failed standard first- and second-line therapies. Despite advancements in targeted therapies, options for third-line treatments are limited, with current regimens such as regorafenib, fruquintinib, and TAS-102 demonstrating modest efficacy. The RS regimen, combining raltitrexed and S-1, has shown improved objective response rates (ORR) and progression-free survival (PFS) compared to standard therapies. Fruquintinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, has also demonstrated efficacy in heavily pretreated mCRC patients, including those resistant to prior anti-VEGF therapies. Combining these agents in the RSF regimen leverages complementary mechanisms of action to address resistance and improve outcomes. Methods: This multicenter, prospective, single-arm, open-label Phase II clinical trial evaluates the efficacy and safety of the RSF regimen in mCRC patients who have failed first- and second-line therapies. Eligible patients will receive S-1 orally (14 days), raltitrexed intravenously (day 1), and fruquintinib orally (14 days) in a 21-day cycle. The primary endpoint is ORR, assessed using RECIST v1.1 criteria. Secondary endpoints include PFS, overall survival (OS), disease control rate (DCR), and quality of life (QoL). Safety will be monitored per NCI-CTCAE v4.0 criteria. Discussion: The RSF regimen represents a novel approach to third-line treatment in mCRC, integrating chemotherapy and targeted therapy to enhance tumor response while managing toxicity. By leveraging complementary mechanisms of action, this study aims to optimize therapeutic outcomes in heavily pretreated patients. Further clinical research is essential to validate efficacy, safety, and potential biomarkers for patient selection. Trial registration: ClinicalTrials.gov identifier: NCT06427005, registered on 19 June 2024. [ABSTRACT FROM AUTHOR]

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]

Purpose: Body weight loss after surgery for gastric cancer is related to S-1 compliance and it also affects the prognosis. However, it is unclear whether the preoperative skeletal muscle mass affects S-1 completion for gastric cancer. We investigated the impact of preoperative skeletal muscle mass loss on the completion of S-1 adjuvant chemotherapy for gastric cancer. Methods: We retrospectively analyzed data from 53 patients who underwent curative gastrectomy followed by adjuvant S-1 monotherapy for pStage II–III gastric cancer between 2012 and 2021 at our hospital. The psoas muscle mass index (PMI) was used as the index for preoperative skeletal muscle mass. Results: Thirty-six patients completed S-1 treatment and 17 discontinued treatment. The patients who completed S-1 treatment had a longer overall survival than those who discontinued treatment (log-rank test, p = 0.043). According to a univariate analysis, the patients in the discontinuation group had a significantly lower preoperative body mass index (< 22.9 kg/m2, p = 0.005) and a higher rate of adverse events (grade 2 or higher, p < 0.001) than those in the completion group. According to a multivariate analysis, preoperative PMI (HR 3.563, p = 0.030) was an independent predictive factor for S-1 completion. Conclusion: Preoperative skeletal muscle loss might therefore prevent the completion of adjuvant chemotherapy S-1 in patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Background: It is essential to ensure optimal adherence to adjuvant chemotherapy regimens following gastric cancer surgery. However, treatment intensity for S-1 as adjuvant chemotherapy has not as yet been compared between minimally invasive (MI) and open (Open) surgery. Methods: We retrospectively compared dose modification of adjuvant S-1 between MI and Open surgery in patients undergoing R0 gastrectomy for gastric or esophago-gastric junction cancer at the Cancer Institute Hospital Tokyo, Japan, during the period from 2012 to 2022, and receiving S-1 for pStage II or S-1 plus docetaxel for pStage III as adjuvant chemotherapy. Propensity score matching (PSM) was conducted to adjust for possible confounders. Results: In total, 323 patients were initially included. After PSM, 158 patients remained, 79 in each group. The adjuvant chemotherapy completion rates were similar in the two groups. However, the proportion of patients who required S-1 dose reduction was significantly lower in the MI than in the Open group (43.0% vs. 65.8%, p = 0.004). In addition, the MI group had significantly fewer patients requiring suspension of S-1 than the Open group (46.8% vs. 64.6%, p = 0.025). Moreover, the frequency of adverse events of grade ≥ 3 was significantly lower in the MI than in the Open group (17.7% vs. 31.7%, p = 0.042). Conclusions: In adjuvant chemotherapy for gastric cancer, minimally invasive surgery may offer better treatment intensity for oral S-1 administration than open surgery. [ABSTRACT FROM AUTHOR]

Purpose The prognosis for type 4 and large type 3 gastric cancer (GC) is extremely poor, especially in elderly patients (≥ 75 years). To improve the prognosis of these types of GC, we performed a phase I study to determine the recommended dose (RD) of S-1 combined with neoadjuvant radiotherapy. Methods Patients with clinically resectable type 4 and large type 3 GC were enrolled to successive cohorts in a conventional 3 + 3 design. Three dose levels were designed, as follows: level 0: S-1 60 mg/m2/day on Days 1–14; level 1: S-1 80 mg/m2/day on Days 1 –14; level 2: S-1 80 mg/m2/day on Days 1–14 and Days 22–35. The starting dose was level 1. Radiotherapy was delivered at a total dose of 40 Gy in fractions for 4 weeks. Results Ten patients were enrolled from July 2014 to August 2018. Six patients were registered at level 1, and one patient developed a dose limiting toxicity as gastric stenosis (grade 3). Two of four patients enrolled at level 2 developed dose limiting toxicity (inability to receive S-1 for hematological reasons). Therefore, the RD was determined as level 1. All patients underwent the protocol surgery; one patient underwent R1 resection because of positive peritoneal washing cytology. There were no treatment-related deaths, and the pathological response rate was 80%. The 5-year overall- and progression-free survival rates were both 60.0%. Conclusion The RD was determined as level 1. A phase II trial using the RD should be initiated. [ABSTRACT FROM AUTHOR]

Background: To improve the prognosis of clinically resectable type 4 or large type 3 gastric cancer (GC), we performed a phase I/II study of neoadjuvant-radiotherapy combined with S-1 plus cisplatin. Patients and Methods: Phase I, with a standard 3 + 3 dose-escalation design, was performed to define the recommended phase II dose. Efficacy and safety were evaluated in phase II. The three dose levels were as follows: level 0, S-1 60 mg/m2 on days 1–14 plus cisplatin 60 mg/m2 on day 1; level 1, S-1 80 mg/m2 on days 1–14 plus cisplatin 60 mg/m2 on day 1; and level 2, S-1 80 mg/m2 on days 1–14 and 22–35, plus cisplatin 60 mg/m2 on days 1 and 22. The starting dose was level 1. Radiotherapy was delivered at a total dose of 40 Gy in fractions for 4 weeks. Results: A total of six patients were enrolled in the phase I study. Dose-limiting toxicity was observed at level 2; level 1 was established as the recommended phase II dose. In phase II, 20 patients were enrolled from November 2012 to April 2018. Grade 3/4 leukopenia and nonhematologic adverse events occurred in 35% and 5% of the patients, respectively. In total, 19 patients underwent the protocol surgery; 2 (10.5%) achieved a pathological complete response. There were no treatment-related deaths; 3- and 5-year overall survival rates were 70.0 and 50.0%, respectively. Conclusions: Neoadjuvant chemoradiotherapy with S-1 plus cisplatin is a safe and promising treatment for clinically resectable type 4 or large type 3 GC. [ABSTRACT FROM AUTHOR]

Abstract Purpose Reports on the association of perioperative nutritional and inflammatory status with the clinical course of adjuvant chemotherapy did not include neoadjuvant chemotherapy. We aimed to clarify the mechanism by which perioperative nutritional and inflammatory status affect the clinical course of postoperative adjuvant chemotherapy in patients with pancreatic cancer. Methods We enrolled 123 patients with pancreatic cancer retrospectively who underwent surgical resection with neoadjuvant and S-1 adjuvant chemotherapy between January 2013 and December 2022. The duration of continuing S-1 treatment and the continuation rates at 3 and 6 months after initiating adjuvant chemotherapy were calculated using the Kaplan–Meier method. The log-rank test was used to evaluate statistical differences between the high and low prognostic nutritional index (PNI) groups. Univariable and multivariable analyses were performed to determine the risk factors for continuing S-1 adjuvant chemotherapy. Results The optimal cut-off value for preoperative PNI was 45. Preoperative PNI was an independent risk factor for continuing S-1 adjuvant chemotherapy in patients who underwent perioperative adjuvant chemotherapy and surgical resection (hazard ratio = 2.435, 95% confidence interval = 1.229 − 4.824, p = 0.011). Low PNI was associated with lower S-1completion (p = 0.02) and higher S-1 withdrawal (p = 0.031). Additionally, the preoperative PNI status affected ≥ grade 2 adverse events caused by adjuvant chemotherapy (p

Introduction: Nanoliposomal irinotecan (nal-IRI) + 5-fluorouracil (FU)/leucovorin (LV) is the new standard second-line therapy for advanced pancreatic cancer (PC). Tegafur, gimeracil, and oteracil potassium (S-1) have been used in advanced PC after gemcitabine (GEM) plus nab-paclitaxel treatment, but the clinical difference between nal-IRI+5-FU/LV and S-1 remains unclear. Methods: We retrospectively compared the efficacy and safety of nal-IRI+5-FU/LV and S-1 in patients with advanced PC refractory to GEM plus nab-paclitaxel. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. Results: We analyzed patients with advanced PC who were refractory to GEM plus nab-paclitaxel from May 2015 to January 2022 at our hospital. Twelve patients treated with nal-IRI+5-FU/LV and 51 patients treated with S-1 were included in this study. Comparing the nal-IRI+5-FU/LV and S-1 groups, the median PFS was 2.95 months versus 2.10 months (p = 0.658), respectively, and the median OS was 8.51 months versus 5.83 months (p = 0.763), respectively. The ORR and DCR were 8.3% and 2.0% (p = 0.347) and 58.3% and 49.0% (p = 0.750) for the nal-IRI+5-FU/LV and S-1 groups, respectively. There were no significant differences in adverse events between the two groups. In a subgroup analysis, patients under 65 years of age treated with S-1 had a significantly better median OS (HR, 3.46; 95% CI: 1.02–11.71, p = 0.046). Conclusion: Nal-IRI+5-FU/LV and S-1 were equally effective and safe as second-line therapy for PC. However, the results suggest that S1 is an option for younger patients, especially those under 65 years. [ABSTRACT FROM AUTHOR]

Purpose: In our previous study, we found that the Chk1 inhibitor prexasertib enhances the antitumour effect of the oral anticancer drug S-1 against pancreatic cancer cells. In this study, we investigated the effect of combining S-1 and ceralasertib, an oral inhibitor of ATR, which is located upstream of Chk1. Ceralasertib is currently being investigated in multiple clinical trials for various cancers. Methods: The cell-proliferation inhibitory effect was measured by MTT assay, using the pancreatic cancer cell lines BxPC-3, SUIT-2, PANC-1, and MIA PaCa-2, while apoptosis was measured by flow cytometry using PI/Annexin staining. The mechanism underlying the combined effect was analysed using western blotting, and the antitumor effect was analysed using a mouse xenograft model. Results: MTT assay revealed that the combination of S-1 and ceralasertib had a synergistic effect, leading to the suppression of cell proliferation. Measurement with PI/Annexin staining revealed that the combination of S-1 and ceralasertib induced apoptosis more efficiently than either drug alone. Western blotting results showed that ceralasertib inhibited S-1-induced activation of ATR and Chk1. The average estimated tumour volume after 3 weeks of administration was 601 mm3 in the S-1 group, 580 mm3 in the ceralasertib group, and 298 mm3 in the combination group. Conclusion: The combination of S-1 and ceralasertib demonstrated a high antiproliferative effect in inhibiting tumour growth in vitro. [ABSTRACT FROM AUTHOR]

Background: S‐1, an oral fluoropyrimidine derivative, is standard adjuvant therapy for resected biliary tract cancer (BTC), based on the results of the JCOG1202, a phase III trial evaluating the survival benefit with adjuvant S‐1 following curative resection for BTC compared to surgery alone. This multicenter ancillary study of the JCOG1202 aimed to evaluate the prognostic impact of the 5‐fluorouracil (5‐FU) metabolic pathway genes including thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD). Methods: The 5‐FU metabolic pathway genes were measured in tumor cells from formalin‐fixed paraffin‐embedded resected specimens from 183 patients (surgery alone: n = 94; adjuvant S‐1: n = 89). We randomly divided them into training (n = 96) and validation sets (n = 87) for evaluating the interaction between gene levels and RFS benefits in the treatment arm. Results: RFS benefits of adjuvant S‐1 were observed in the low DPD (HR = 0.440 and 0.748, respectively in the training and validation sets) and the low TP groups (HR = 0.709 and 0.602, respectively). Clinicopathological characteristics were well balanced between low and high DPD populations. More advanced stage tumors were observed in high TP populations as compared to those in low TP populations (p =.0332). Conclusion: The results suggest the RFS benefit of adjuvant S‐1 in resected BTC patients with low DPD and low TP gene expressions. [ABSTRACT FROM AUTHOR]

Purpose: The clinical effectiveness of triple chemotherapy consisting of gemcitabine, cisplatin plus either S-1 (GCS), durvalumab (DGC), or pembrolizumab (PGC) as first-line treatment for advanced biliary tract cancer (BTC) has been reported. However, their comparative cost-effectiveness is unclear. We conducted a model-based cost-effectiveness analysis from the perspective of Japanese healthcare payer. Methods: A 10-year partitioned survival model was constructed by comparing the time-dependent hazards of the KHBO1401-MITSUBA, TOPAZ-1, and KEYNOTE-966 trials. The cost and utility came from previously published reports. Quality-adjusted life years (QALY) were used to measure the effects on health. Costs for direct medical care were taken into account. There was a one-way analysis and a probability sensitivity analysis. A willingness-to-pay threshold of 7.5 million yen (57,034 USD) per QALY was defined. Results: The incremental costs per QALY for GCS, DGC, and PGC in the base case study were 3,779,374 JPY (28,740 USD), 86,058,056 JPY (65,4434 USD), and 28,982,059 JPY (220,396 USD), respectively. No parameter had an influence beyond the threshold in a one-way sensitivity analysis. A probabilistic sensitivity analysis revealed that the probability of GCS, DGC, and PGC being cost-effective at the threshold was 85.6%, 0%, and 0%, respectively. Conclusion: Given the current circumstances, it is probable that triple therapy utilizing GCS will emerge as a plausible and efficient primary chemotherapy strategy for patients with advanced BTC in the Japanese healthcare system, as opposed to DGC and PGC. [ABSTRACT FROM AUTHOR]

Aim: Gastric cancer is the third leading cause of cancer-related mortality and the fifth most common cancer globally. In China, many patients are diagnosed at an advanced stage and cannot be operated on, so the prognosis is very poor. The role of maintenance therapy after first-line chemotherapy in gastric cancer is still unclear. Apatinib is a small-molecule VEGFR-2 TKI and is currently approved for third-line treatment after failure of second-line chemotherapy for advanced gastric cancer. In this article, we use case reports to illustrate its effectiveness and to study what effective maintenance treatments are available for gastric cancer. Methods: The main treatment is chemotherapy and targeted therapy. We reported a 68-year-old man with a diagnosis of advanced gastric cancer with liver metastasis. From 12/2014 to 05/2015 Oxaliplatin + S-1(dose) chemotherapy for 6 cycles, the efficacy of partial response (PR) evaluation. After the patient's oral S-1 + Apatinib (dose) to maintain the therapeutic usage and dosage, the patient is well tolerated, the tumor is reviewed regularly, and the condition is stable. The patient was finally infected with the COVID-2019 in May 2023, resulting in death after ineffective treatment. Results: After Oxaliplatin combined with S-1 regimen, the effect was up to PR. S-1 combined with Apatinib maintenance therapy after first-line chemotherapy, the patient has survived for more than 7 years without progression. Conclusions: The current treatment of advanced gastric cancer is not satisfactory. The combined application of S-1 and Apatinib in gastric cancer maintenance therapy deserves further study. Maintenance therapy for gastric cancer has attracted wide attention, and more large-scale clinical research is under way. [ABSTRACT FROM AUTHOR]

Purpose: Reports on the association of perioperative nutritional and inflammatory status with the clinical course of adjuvant chemotherapy did not include neoadjuvant chemotherapy. We aimed to clarify the mechanism by which perioperative nutritional and inflammatory status affect the clinical course of postoperative adjuvant chemotherapy in patients with pancreatic cancer. Methods: We enrolled 123 patients with pancreatic cancer retrospectively who underwent surgical resection with neoadjuvant and S-1 adjuvant chemotherapy between January 2013 and December 2022. The duration of continuing S-1 treatment and the continuation rates at 3 and 6 months after initiating adjuvant chemotherapy were calculated using the Kaplan–Meier method. The log-rank test was used to evaluate statistical differences between the high and low prognostic nutritional index (PNI) groups. Univariable and multivariable analyses were performed to determine the risk factors for continuing S-1 adjuvant chemotherapy. Results: The optimal cut-off value for preoperative PNI was 45. Preoperative PNI was an independent risk factor for continuing S-1 adjuvant chemotherapy in patients who underwent perioperative adjuvant chemotherapy and surgical resection (hazard ratio = 2.435, 95% confidence interval = 1.229 − 4.824, p = 0.011). Low PNI was associated with lower S-1completion (p = 0.02) and higher S-1 withdrawal (p = 0.031). Additionally, the preoperative PNI status affected ≥ grade 2 adverse events caused by adjuvant chemotherapy (p < 0.001). Conclusion: Preoperative PNI affected adjuvant chemotherapy continuation and related adverse events in patients who underwent neoadjuvant chemotherapy and curative resection. Additional perioperative anti-inflammatory management and nutritional support may be required to improve the clinical course of postoperative adjuvant chemotherapy and patient survival. [ABSTRACT FROM AUTHOR]

Background: Recently, the clinical benefits of neoadjuvant chemotherapy combined with immunotherapy have been observed in patients with locally advanced gastric or gastroesophageal junction (G/GEJ) cancer; however, the pathological complete response (pCR) and long-term survival rates are still unsatisfactory. The aim of this study is to investigate the efficacy and safety of chemotherapy combined with tislelizumab and low-dose radiation therapy (LDRT) for the neoadjuvant treatment of locally advanced G/GEJ cancer. Methods: This is a prospective, multicenter, single-arm, phase Ib/II trial. In the phase Ib study, 5 patients will be enrolled in each treatment group with different radiation doses. In the phase II study, a total of 44 patients will be enrolled. Eligible patients will be registered and receive three cycles of SOX regimen chemotherapy (S-1: 40-60 mg Bid, d1-14, q3w; oxaliplatin: 130 mg/m2, iv drip, d1, q3w) plus tislelizumab (200 mg, iv drip, d1, q3w). Simultaneously, LDRT will be planned and administered after the first cycle of systemic therapy. Radical D2 gastrectomy will be performed 4-6 weeks after the last administration of chemotherapy plus tislelizumab. The primary endpoint of phase Ib study is to determine the optimal radiation dose for phase II study. The primary endpoint of phase II is the pCR rate. The secondary endpoints include R0 resection rate, major pathological response (MPR) rate, 2-year event-free survival (EFS) rate, 2-year overall survival (OS) rate and safety profile. Moreover, we will also explore potential molecular markers for predicting the benefit and safety of this neoadjuvant regimen. Written informed consent should be provided by all patients enrolled in the study. The study protocol was approved by the independent ethics committee at each institution. Discussion: This is the first study to explore the efficacy and safety of neoadjuvant chemotherapy combined with tislelizumab and LDRT in G/GEJ cancer patients, the results of which may provide novel treatment strategy for patients with locally advanced G/GEJ adenocarcinoma. Clinical trial registration: ClinicalTrials.Gov , identifier NCT06266871. [ABSTRACT FROM AUTHOR]

Objectives: Literature data are scarce on concurrent chemoradiotherapy (CCRT) with S-1 for locally advanced nasopharyngeal carcinoma (LANPC) treatment. This study compared the efficacy and safety of the S-1 versus platinum-based CCRT in LANPC treatment. Methods: This study enrolled 547 patients newly diagnosed with LANPC who underwent CCRT with S-1 or platinum at three institutions. Propensity score matching in a 1:1 ratio balancing baseline features was performed. Survival and adverse effects were compared between groups. Results: Of 160 patients in the cohort, 100 eligible were propensity score matched. Matched dataset analyses showed a higher 5-year overall survival rate (87.1% vs. 84.7%, P = 0.833), progression-free survival (79.6% vs. 75.5%, P = 0.669), locoregional recurrence-free survival (87.0% vs. 84.7%, P = 0.518), and distant metastasis-free survival (84.8% vs. 83.0%, P = 0.780) in the S-1 group than in the platinum-based CCRT group, although not statistically significant. Objective response rate (98.0% vs. 88.0%, P = 0.117) was significantly higher in the S-1 than in the platinum-based regimen, although it was not statistically reflected. Compared with platinum-based, those undergoing S-1-based chemotherapy demonstrated a higher incidence of grade 3 mucositis (20.0% vs. 2.0%, P = 0.016) in the S-1 group and a lower incidence of leukopenia (44.0% vs. 68.0%, P = 0.033), neutropenia (28.0% vs. 52.0%, P = 0.032), anemia (22.0% vs. 44.0%, P = 0.040), nephrotoxicity (4.0% vs. 20.0%, P = 0.028), and nausea/vomiting (30.0% vs. 56.0%, P = 0.019). Conclusion: The results suggest that S-1 can be used as a concurrent chemotherapy regimen during radiotherapy for patients with LANPC, since it presents a noninferior survival benefit compared with platinum and shows tolerable adverse effects. [ABSTRACT FROM AUTHOR]

Objective To evaluate the clinical efficacy and safety of different chemotherapeutic regimens combined with sintilimab as first-line treatment for Her-2 negative advanced gastric cancer. Methods We retrospectively collected the clinical data of patients with Her-2 negative advanced gastric cancer treated with albumin-bound paclitaxel plus S-1 combined with sintilimab (n=40) and oxaliplatin plus S-1 combined with sintilimab (n=36) at The Affiliated Hospital of Xuzhou Medical University from September 1, 2021 to July 1, 2023. The clinical efficacy and adverse reactions were evaluated separately in patients treated with albumin-bound paclitaxel plus S-1 combined with sintilimab and in those treated with oxaliplatin plus S-1 combined with sintilimab. Factor analysis was made on two sets of clinical data separately. Results The objective response rate (ORR) of albumin-bound paclitaxel group and oxaliplatin group was 57. 5％and 52. 8％, respectively. The disease control rate (DCR) of albumin-bound paclitaxel group and oxaliplatin group was 85. 0％and 80. 6％, respectively. The median progression-free survival (PFS) of patients in albumin-bound paclitaxel group and oxaliplatin group was 8. 3 months and 9. 0 months. The incidence of adverse reactions in albumin-bound paclitaxe group was 87. 5％ (35/40), and that in the oxaliplatin group was 91. 7％ (33/36). Factor analysis of the clinical data of albumin-bound paclitaxel group and oxaliplatin group revealed that liver metastasis was an independent risk factor for PFS. Conclusion Both albumin-bound paclitaxel combined with S-1 and sintilimab, and oxaliplatin combined with S-1 and sintilimab show promising efficacy and manageable side effects when used as first-line treatment for Her-2 negative advanced gastric cancer. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the efficacy and safety of using metronomic S-1 adjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma (LANPC). Materials and Methods: We retrospectively collected data on patients diagnosed with LANPC between January 2016 and December 2021. All patients were treated with induction chemotherapy and concurrent chemoradiotherapy with or without metronomic chemotherapy (MC). Toxicities during MC were recorded. The chi-square test, Kaplan-Meier methods, propensity score matching (PSM), and Cox proportional hazards model were used for statistical analyses. Results: A total of 474 patients were identified, including 64 (13.5%) and 410 (83.5%) patients with or without receiving MC, respectively. Patients who received metronomic S-1 had significantly better 3-year locoregional recurrence-free survival (LRFS) (100% vs. 90.9%, p=0.038), distant metastasis-free survival (DMFS) (98.5% vs. 84.1%, p=0.002), disease-free survival (DFS) (98.4% vs. 77.5%, p < 0.001), and overall survival (OS) (98.0% vs. 87.7%, p=0.008) compared to those without metronomic S-1. The multivariate prognostic analysis revealed that metronomic S-1 was identified as an independent prognostic factor associated with better DMFS (hazard ratio [HR], 0.074; p=0.010), DFS (HR, 0.103; p=0.002) and OS (HR, 0.127; p=0.042), but not in LRFS (p=0.071). Similar results were found using PSM. Common adverse events observed in the metronomic S-1 group included leukopenia, neutropenia, increased total bilirubin, anorexia, rash/desquamation, and hyperpigmentation. All patients with adverse events were grade 1-2. Conclusion: It is worth conducting a randomized controlled trial to assess the effect of metronomic S-1 on survival outcomes and toxicities of LANPC. [ABSTRACT FROM AUTHOR]

Simple Summary: Adjuvant chemotherapy (AC) using S-1 has demonstrated favorable outcomes for patients with pancreatic cancer (PC). However, the current S-1 completion rate is insufficient to achieve its benefits. Moreover, an absence of dependable markers to forecast S-1 completion warrants C-reactive protein-to-albumin ratio (CAR) investigation as a potential predictive factor related to nutritional status. Previously, we revealed that a postoperative CAR value of ≥0.05 serves as a marker predicting S-1 AC treatment non-completion due to adverse events (AEs) in the Ehime study. Thus, this study aims to substantiate the correlation between postoperative CAR and S-1 therapy non-completion due to AEs using an alternative cohort from another institution (the Dokkyo study). Background: S-1 in adjuvant chemotherapy (AC) administration after pancreatic cancer (PC) surgery has been standardized in Japan. The Ehime study confirmed that a postoperative higher C-reactive protein-to-albumin ratio (CAR) value predicted the risk of adverse event (AE)-related S-1 non-completion as an AC in patients with PC after curative surgery. This study aimed to investigate the index to predict S-1 tolerance among patients who underwent curative surgery for PC (the Dokkyo study). Methods: This retrospective validation cohort study included 172 patients at the Department of Hepato-Biliary Pancreatic Surgery, Dokkyo Medical University, Japan, from January 2010 to December 2022. All patients underwent nutritional screening using the postoperative CAR. S-1 completion status and its effect on prognosis were systematically followed up and investigated. We conducted a statistical analysis of predictive markers to investigate their association with S-1 completion. Results: Patients were categorized into the S-1 completion (N = 91) and non-completion (N = 81) groups. The S-1 completion group demonstrated a significantly lower CAR than the S1 non-completion group. Moreover, the current study revealed a significant difference in the S-1 completion rate, applying the CAR cutoff value of 0.05 established in the Ehime study. Additionally, univariate and multivariate analyses confirmed that a CAR of <0.05 was significantly associated with S-1 completion. Conclusions: The Dokkyo study confirmed the results observed in the Ehime study. Consequently, an increased postoperative CAR value appeared as a universal applicable marker for the risk factor of AE-related S-1 non-completion after curative surgery for patients with PC. [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]

ObjectiveS-1, an oral multicomponent capsule containing tegafur, gimeracil, and potassium oxonate, has demonstrated efficacy in various tumor types. This study aimed to assess the pharmacokinetics, bioequivalence (BE), and safety of a newly developed generic S-1 capsule compared to the original brand-name formulation in Chinese cancer patients under fasting and fed conditions.MethodsA multicenter, randomized, open-label, single-dose, double-cycle crossover study was conducted in Chinese cancer patients. The study involved 120 subjects, with 60 assigned to the fasting group and another 60 to the fed group. In each study cycle, subjects were randomly assigned toreceive either the reference or test S-1 capsule at a 7-day interval. Blood samples were collected for analysis within 48 h after ingestion. The plasma concentrations of tegafur, 5-fluorouracil, gimeracil, and potassium oxonate were determined by liquid chromatography–tandem mass spectrometry (LC-MS/MS). The main pharmacokinetic (PK) parameters were calculated using the non-compartmental approach. BE was assessed through geometric mean ratios (GMRs) between the two formulations and their respective 90% confidence intervals (CIs). The safety of the two formulations was also evaluated.ResultsThe pharmacokinetics of the two formulations were similar under both fasting and fed conditions. The 90% CIs of the GMRs for the maximum observed serum concentration (Cmax), AUC0-t, and AUC0-∞ ratios were observed to lie within the BE acceptance range of 80%–125%. Both formulations of the S-1 capsule exhibited similar adverse events (AEs), primarily including decreased white blood cell count and hypertension. These AEs were generally mild and transient. The safety profiles of the two formulations were found to be good and comparable, with no serious adverse events (SAEs) reported.ConclusionThe newly developed generic S-1 and reference formulations exhibit comparable PK in Chinese cancer patients in the fasting and fed state. The formulations of S-1 showed good tolerability and a similar safety profile.Clinical Trial Registrationhttp://www.chinadrugtrials.org.cn/index.html, identifier CTR20171562.

BackgroundInterstitial 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 reportA 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.ConclusionThis 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 This study aimed to survey the efficacy of chemotherapy regimens in the real world setting and explore the most promising regimen for patients experiencing early recurrence for gastric cancer. We retrospectively reviewed the clinical course of 207 patients with gastric cancer, who developed early recurrence during or within 6 months after completing S-1 adjuvant therapy at 19 Japanese institutions between 2012 and 2016. The treatment regimens after recurrence were fluoropyrimidines plus platinum-based regimens (FP) in 91 (44%) patients, paclitaxel-based regimens (PTX) in 102 (49%), and irinotecan-based regimens (IRI) in 14 (7%). The overall response and disease control rates were 28.7% and 54.1%. Median progression-free survival (PFS) and overall survival (OS) were 5.1 and 12.9 months, respectively. In the FP, PTX, and IRI regimens, the median PFS and OS were 5.9, 4.1, 4.1 months and 12.8, 12.9, and 11.8 months, respectively. The combination of PTX and ramucirumab showed survival comparable to capecitabine plus platinum. Multivariate analyses for OS showed that recurrence during adjuvant chemotherapy and undifferentiated histological type were independent poor prognostic factors. Although the prognosis of patients with early recurrence even with adjuvant S-1 was poor, PTX plus ramucirumab therapy could be a potential treatment option.

Pancreatic acinar cell carcinoma (PACC) represents a rare malignancy within the pancreatic tumor spectrum. Owing to its rarity, the establishment of a standardized chemotherapy regimen for patients presenting with either metastatic disease or recurrence after radical surgery remains elusive. Most previous studies and case reports have used gemcitabine-based and 5-fluorouracil-based regimens, however, no previous study has reported the use of liposomal irinotecan in combination with S-1. In this report, we present a patient with PACC who experienced disease progression with liver metastasis after radical tumor resection followed by chemoradiotherapy. The patient underwent second-line treatment with liposomal irinotecan in conjunction with S-1. Encouragingly, the patient has remained free of recurrence and progression during a follow-up period of 2 years and 3 months.

Abstract Objective Explore the efficacy and safety of involved-field irradiation (IFI) combined with S-1 as definitive concurrent chemoradiotherapy (dCRT) for locally advanced elderly esophageal squamous cell carcinoma (ESCC), under the premise of intensity-modulated radiotherapy (IMRT). Methods We designed a prospective single-arm phase II study. The study enrolled 91 patients aged 75 to 92 years. Eligible participants had histologically confirmed squamous cell carcinoma, stage II to IV disease based on the 8th edition of the American Joint Committee on Cancer (AJCC). All elderly patients (EPs) received dCRT with S-1. which was administered orally twice daily for 28 days. The radiotherapy dose was 61.2 Gy delivered in 34 fractions or 50.4 Gy delivered in 28 fractions. The primary endpoint was 2-year overall survival (OS), and the secondary endpoints were progression-free survival (PFS), local control rate (LCR), and safety. Results From July 2017 to July 2021, we enrolled EPs with ESCC who were treated at the Jiangsu Cancer hospital. As of August 1, 2023, the median follow-up of surviving EPs was 31.4 months (IQR: 25.2 to 72.6 months). 83 patients (91.2%) completed the whole course of treatment. The 2-year OS rate was 59.2%, and the PFS rate was 43.7%. The most common grade 1 to 2 adverse effects (AEs) were radiation esophagitis (79.1%), and then were radiation pneumonia (46.2%). Anemia (41.8%) was the most common of grade 1 to 2 hematologic toxicity. The incidence of grade 3 or above AEs was 24.2%, and the incidence of leukopenia was the highest (11.0%). There was not one death due to treatment-related toxicity. In a subgroup analysis of radiotherapy doses, we found no statistically significant differences in PFS (P = 0.465) and OS (P = 0.345) in EPs with ESCC who received 50.4 Gy and 61.2 Gy, and that patients in the 50.4 Gy group had lower dermatitis (P = 0.045) and anemia (P = 0.004). Conclusions IF-IMRT combined with S-1 is a promising regimen for elderly ESCC. And the radiotherapy dose of 50.4 Gy remains the standard dose for EPs with ESCC undergoing CCRT.

Abstract Adjuvant oxaliplatin plus S-1 (SOX) chemotherapy for gastric cancer (GC) after D2 gastrectomy has been proven effective. There has yet to be a study that evaluates adjuvant nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus S-1. In this single-center, retrospective study, GC patients after D2 gastrectomy received either nab-paclitaxel plus S-1 (AS group) or SOX group were recruited between January 2018 and December 2020 in The First Affiliated Hospital of Zhejiang University. Intravenous nab-paclitaxel 120 mg/m2 or 260 mg/m2 and oxaliplatin 130 mg/m2 were administered as eight 3 week cycle, especially in the AS and SOX group. Patients received S-1 twice daily with a dose of 40 mg/m2 in the two groups on days 1–14 of each cycle. The end points were disease-free survival (DFS) rate at 3 years and adverse events (AEs). There were 56 eligible patients, 28 in the AS group and 35 in the SOX group. The 3 year DFS rate was 78.0% in AS group versus 70.7% in SOX group (p = 0.46). Subgroup analysis showed that the patients with signet-ring positive in the AS group had a prolonged DFS compared with the SOX group (40.0 vs. 13.8 m, p = 0.02). The diffuse-type GC or low differentiation in the AS group was associated with numerically prolonged DFS compared with the SOX group, but the association was not statistically significant (p = 0.27 and p = 0.15 especially). Leukopenia (14.3%) were the most prevalent AEs in the AS group, while thrombocytopenia (28.5%) in the SOX group. Neutropenia (7.1% in AS group) and thrombocytopenia (22.8% in SOX group) were the most common grade 3 or 4 AEs. In this study analyzing past data, a tendency towards a greater 3 year DFS was observed when using AS regimen in signet-ring positive patients. AS group had fewer thrombocytopenia compared to SOX group. More studies should be conducted with larger sample sizes.

Abstract This study aimed to compare second-line treatment outcomes for patients with unresectable pancreatic cancer previously treated with gemcitabine plus nab–paclitaxel (GnP) therapy. We conducted an integrated analysis of two retrospective studies included 318 patients receiving nanoliposomal irinotecan + 5-fluorouracil/folinic acid (NFF) (n = 102), S-1 (n = 57), or FOLFIRINOX (n = 14) as second-line treatment. Median overall survival (OS) in the NFF group was 9.08 months, significantly better than S-1 (4.90 months, P = 0.002). FOLFIRINOX had a median OS of 4.77 months, not statistically different from NFF. Subgroup analyses of OS indicated NFF was generally superior, however, a statistical interaction was observed between the treatment regimen in serum Alb

Background: This study aims to compare the effectiveness and safety of the combination of raltitrexed, S‐1 (RS), and fruquintinib with the combination of RS and bevacizumab in patients with refractory metastatic colorectal cancer (mCRC). Methods: This retrospective cohort included mCRC patients who received the RS plus fruquintinib or regorafenib as the third‐line therapy from May 2019 to April 2023. A propensity score matching (PSM) analysis was used to balance the baseline characteristics of all patients. Overall survival (OS), progression‐free survival (PFS), tumor response, and safety of the two regimens were evaluated. Results: Of the 153 patients enrolled, 123 patients received the RS plus bevacizumab and 30 patients received the RS plus fruquintinib. After PSM, 30 pairs were analyzed. Patients treated with RS plus fruquintinib had a longer PFS than those treated with RS plus bevacizumab before PSM (5.0 months vs. 4.3 months, p = 0.008) and after PSM (5.0 months vs. 4.4 months, p = 0.012). A longer OS was also observed in RS plus fruquintinib group before PSM and after PSM, but there was no statistic difference between two groups after PSM. Both objective response rate and disease control rate were higher in the RS plus fruquintinib cohort than those in the RS plus bevacizumab cohort before PSM, and the difference in values between the two groups reduced after PSM. The adverse effects (AEs) of both groups were well tolerated. Conclusion: In patients with refractory mCRC, RS plus fruquintinib demonstrated a superior OS, PFS than RS plus bevacizumab and had manageable AEs. [ABSTRACT FROM AUTHOR]

Objective: Explore the efficacy and safety of involved-field irradiation (IFI) combined with S-1 as definitive concurrent chemoradiotherapy (dCRT) for locally advanced elderly esophageal squamous cell carcinoma (ESCC), under the premise of intensity-modulated radiotherapy (IMRT). Methods: We designed a prospective single-arm phase II study. The study enrolled 91 patients aged 75 to 92 years. Eligible participants had histologically confirmed squamous cell carcinoma, stage II to IV disease based on the 8th edition of the American Joint Committee on Cancer (AJCC). All elderly patients (EPs) received dCRT with S-1. which was administered orally twice daily for 28 days. The radiotherapy dose was 61.2 Gy delivered in 34 fractions or 50.4 Gy delivered in 28 fractions. The primary endpoint was 2-year overall survival (OS), and the secondary endpoints were progression-free survival (PFS), local control rate (LCR), and safety. Results: From July 2017 to July 2021, we enrolled EPs with ESCC who were treated at the Jiangsu Cancer hospital. As of August 1, 2023, the median follow-up of surviving EPs was 31.4 months (IQR: 25.2 to 72.6 months). 83 patients (91.2%) completed the whole course of treatment. The 2-year OS rate was 59.2%, and the PFS rate was 43.7%. The most common grade 1 to 2 adverse effects (AEs) were radiation esophagitis (79.1%), and then were radiation pneumonia (46.2%). Anemia (41.8%) was the most common of grade 1 to 2 hematologic toxicity. The incidence of grade 3 or above AEs was 24.2%, and the incidence of leukopenia was the highest (11.0%). There was not one death due to treatment-related toxicity. In a subgroup analysis of radiotherapy doses, we found no statistically significant differences in PFS (P = 0.465) and OS (P = 0.345) in EPs with ESCC who received 50.4 Gy and 61.2 Gy, and that patients in the 50.4 Gy group had lower dermatitis (P = 0.045) and anemia (P = 0.004). Conclusions: IF-IMRT combined with S-1 is a promising regimen for elderly ESCC. And the radiotherapy dose of 50.4 Gy remains the standard dose for EPs with ESCC undergoing CCRT. [ABSTRACT FROM AUTHOR]

This study aimed to compare second-line treatment outcomes for patients with unresectable pancreatic cancer previously treated with gemcitabine plus nab–paclitaxel (GnP) therapy. We conducted an integrated analysis of two retrospective studies included 318 patients receiving nanoliposomal irinotecan + 5-fluorouracil/folinic acid (NFF) (n = 102), S-1 (n = 57), or FOLFIRINOX (n = 14) as second-line treatment. Median overall survival (OS) in the NFF group was 9.08 months, significantly better than S-1 (4.90 months, P = 0.002). FOLFIRINOX had a median OS of 4.77 months, not statistically different from NFF. Subgroup analyses of OS indicated NFF was generally superior, however, a statistical interaction was observed between the treatment regimen in serum Alb < 3.5 g/dL (P = 0.042) and serum CRP ≥ 0.3 mg/dL (P = 0.006). Median progression-free survival (PFS) was 2.93 months for NFF, significantly better than S-1 (2.53 months, P = 0.024), while FOLFIRINOX had a comparable PFS (3.04 months, P = 0.948). Multivariate analysis identified the serum CRP, serum CA19-9, duration of first-line GnP therapy, and use (yes/no) of S-1 for second-line treatment as independent predictors for OS. This study concludes that second-line NFF therapy demonstrated a more favorable OS compared to S-1 therapy, however, it is still important to consider the patient background characteristics while selecting the most appropriate treatment. [ABSTRACT FROM AUTHOR]

We report here a case of postoperative recurrent adenosquamous carcinoma (ASC) of the esophagogastric junction (EGJ) treated with S-1 therapy. A 79-year-old woman was diagnosed with carcinoma of the EGJ. Thoracoscopic subtotal esophagectomy was performed, and pathological examination revealed advanced ASC with lymph node metastasis. Five months after surgery, multiple lung metastases and multiple lymph node metastases were observed, and the patient was treated with S-1 monotherapy, which showed partial response and may be effective for advanced ASC of the EGJ. On the other hand, immunohistological analysis of the tumors showed a relatively wide range of areas that could differentiate into both adenocarcinoma and squamous cell carcinoma, suggesting that tumor cells with multidifferentiation potential, or at least the ability to differentiate into both adeno-epithelial and squamous epithelial cells, were the likely source of the tumors. [ABSTRACT FROM AUTHOR]

Pancreatic acinar cell carcinoma (PACC) represents a rare malignancy within the pancreatic tumor spectrum. Owing to its rarity, the establishment of a standardized chemotherapy regimen for patients presenting with either metastatic disease or recurrence after radical surgery remains elusive. Most previous studies and case reports have used gemcitabine-based and 5-fluorouracil-based regimens, however, no previous study has reported the use of liposomal irinotecan in combination with S-1. In this report, we present a patient with PACC who experienced disease progression with liver metastasis after radical tumor resection followed by chemoradiotherapy. The patient underwent second-line treatment with liposomal irinotecan in conjunction with S-1. Encouragingly, the patient has remained free of recurrence and progression during a follow-up period of 2 years and 3 months. [ABSTRACT FROM AUTHOR]

Adjuvant oxaliplatin plus S-1 (SOX) chemotherapy for gastric cancer (GC) after D2 gastrectomy has been proven effective. There has yet to be a study that evaluates adjuvant nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus S-1. In this single-center, retrospective study, GC patients after D2 gastrectomy received either nab-paclitaxel plus S-1 (AS group) or SOX group were recruited between January 2018 and December 2020 in The First Affiliated Hospital of Zhejiang University. Intravenous nab-paclitaxel 120 mg/m2 or 260 mg/m2 and oxaliplatin 130 mg/m2 were administered as eight 3 week cycle, especially in the AS and SOX group. Patients received S-1 twice daily with a dose of 40 mg/m2 in the two groups on days 1–14 of each cycle. The end points were disease-free survival (DFS) rate at 3 years and adverse events (AEs). There were 56 eligible patients, 28 in the AS group and 35 in the SOX group. The 3 year DFS rate was 78.0% in AS group versus 70.7% in SOX group (p = 0.46). Subgroup analysis showed that the patients with signet-ring positive in the AS group had a prolonged DFS compared with the SOX group (40.0 vs. 13.8 m, p = 0.02). The diffuse-type GC or low differentiation in the AS group was associated with numerically prolonged DFS compared with the SOX group, but the association was not statistically significant (p = 0.27 and p = 0.15 especially). Leukopenia (14.3%) were the most prevalent AEs in the AS group, while thrombocytopenia (28.5%) in the SOX group. Neutropenia (7.1% in AS group) and thrombocytopenia (22.8% in SOX group) were the most common grade 3 or 4 AEs. In this study analyzing past data, a tendency towards a greater 3 year DFS was observed when using AS regimen in signet-ring positive patients. AS group had fewer thrombocytopenia compared to SOX group. More studies should be conducted with larger sample sizes. [ABSTRACT FROM AUTHOR]

Purpose This prospective study in a real-world setting investigated the feasibility and safety of S-1 plus nimotuzumab (S-1-Nimo) based concurrent chemoradiotherapy (CCRT) in locally advanced esophageal squamous cell carcinoma (LA-ESCC) patients who failed to neoadjuvant chemotherapy or chemoimmunotherapy.Methods LA-ESCC patients who failed to converse to resectable disease after neoadjuvant chemotherapy or chemoimmunotherapy were enrolled to receive the 4-week S-1-Nimo regimen of radiotherapy (40 Gy in 20 fractions, 5 days per week), S-1 chemotherapy, and nimotuzumab. Then, after surgical assessments, patients evaluated as resectable disease received surgery; patients with unresectable disease continued to receive definitive radiotherapy (50–60 Gy in 25–30 fractions, 5 days per week) concurrently with S-1-Nimo. The primary endpoint was event-free survival (EFS).Results Sixty-four patients were enrolled and evaluated. The median follow-up time was 23.2 months. Median EFS was 9.6 (95% confidence interval [CI], 7.1–14.0) months, with an estimated 2-year EFS rate of 24.2%. The median overall survival (OS) and the estimated OS rate at 2 years were 13.4 (95% CI, 10.3–17.5) months and 31.2%, respectively. Twelve underwent surgery, with a surgical conversion rate of 18.8% and an R0 resection rate of 100.0%. Subgroup analysis identified the significantly prolonged EFS and OS in patients who experienced radical surgery (median EFS, not reached vs. 8.7 months; p = .0117. median OS, 24.9 vs. 10.6 months; p = .0205) as compared to those treated with CCRT. Of 64 patients, grade 3 adverse events mainly included radiation esophagitis (4.7%), anemia (1.6%), and thrombocytopenia (1.6%).Conclusion The study demonstrated the reasonable efficacy and promising safety of the S-1-Nimo-based CCRT in LA-ESCC patients with failure to neoadjuvant chemotherapy or chemoimmunotherapy.

AimGastric cancer is the third leading cause of cancer-related mortality and the fifth most common cancer globally. In China, many patients are diagnosed at an advanced stage and cannot be operated on, so the prognosis is very poor. The role of maintenance therapy after first-line chemotherapy in gastric cancer is still unclear. Apatinib is a small-molecule VEGFR-2 TKI and is currently approved for third-line treatment after failure of second-line chemotherapy for advanced gastric cancer. In this article, we use case reports to illustrate its effectiveness and to study what effective maintenance treatments are available for gastric cancer.MethodsThe main treatment is chemotherapy and targeted therapy. We reported a 68-year-old man with a diagnosis of advanced gastric cancer with liver metastasis. From 12/2014 to 05/2015 Oxaliplatin + S-1(dose) chemotherapy for 6 cycles, the efficacy of partial response (PR) evaluation. After the patient’s oral S-1 + Apatinib (dose) to maintain the therapeutic usage and dosage, the patient is well tolerated, the tumor is reviewed regularly, and the condition is stable. The patient was finally infected with the COVID-2019 in May 2023, resulting in death after ineffective treatment.ResultsAfter Oxaliplatin combined with S-1 regimen, the effect was up to PR. S-1 combined with Apatinib maintenance therapy after first-line chemotherapy, the patient has survived for more than 7 years without progression.ConclusionsThe current treatment of advanced gastric cancer is not satisfactory. The combined application of S-1 and Apatinib in gastric cancer maintenance therapy deserves further study. Maintenance therapy for gastric cancer has attracted wide attention, and more large-scale clinical research is under way.

BackgroundRecently, the clinical benefits of neoadjuvant chemotherapy combined with immunotherapy have been observed in patients with locally advanced gastric or gastroesophageal junction (G/GEJ) cancer; however, the pathological complete response (pCR) and long-term survival rates are still unsatisfactory. The aim of this study is to investigate the efficacy and safety of chemotherapy combined with tislelizumab and low-dose radiation therapy (LDRT) for the neoadjuvant treatment of locally advanced G/GEJ cancer.MethodsThis is a prospective, multicenter, single-arm, phase Ib/II trial. In the phase Ib study, 5 patients will be enrolled in each treatment group with different radiation doses. In the phase II study, a total of 44 patients will be enrolled. Eligible patients will be registered and receive three cycles of SOX regimen chemotherapy (S-1: 40-60 mg Bid, d1-14, q3w; oxaliplatin: 130 mg/m2, iv drip, d1, q3w) plus tislelizumab (200 mg, iv drip, d1, q3w). Simultaneously, LDRT will be planned and administered after the first cycle of systemic therapy. Radical D2 gastrectomy will be performed 4-6 weeks after the last administration of chemotherapy plus tislelizumab. The primary endpoint of phase Ib study is to determine the optimal radiation dose for phase II study. The primary endpoint of phase II is the pCR rate. The secondary endpoints include R0 resection rate, major pathological response (MPR) rate, 2-year event-free survival (EFS) rate, 2-year overall survival (OS) rate and safety profile. Moreover, we will also explore potential molecular markers for predicting the benefit and safety of this neoadjuvant regimen. Written informed consent should be provided by all patients enrolled in the study. The study protocol was approved by the independent ethics committee at each institution.DiscussionThis is the first study to explore the efficacy and safety of neoadjuvant chemotherapy combined with tislelizumab and LDRT in G/GEJ cancer patients, the results of which may provide novel treatment strategy for patients with locally advanced G/GEJ adenocarcinoma.Clinical trial registrationClinicalTrials.Gov, identifier NCT06266871.

ObjectivesLiterature data are scarce on concurrent chemoradiotherapy (CCRT) with S-1 for locally advanced nasopharyngeal carcinoma (LANPC) treatment. This study compared the efficacy and safety of the S-1 versus platinum-based CCRT in LANPC treatment. Methods: This study enrolled 547 patients newly diagnosed with LANPC who underwent CCRT with S-1 or platinum at three institutions. Propensity score matching in a 1:1 ratio balancing baseline features was performed. Survival and adverse effects were compared between groups.ResultsOf 160 patients in the cohort, 100 eligible were propensity score matched. Matched dataset analyses showed a higher 5-year overall survival rate (87.1% vs. 84.7%, P = 0.833), progression-free survival (79.6% vs. 75.5%, P = 0.669), locoregional recurrence-free survival (87.0% vs. 84.7%, P = 0.518), and distant metastasis-free survival (84.8% vs. 83.0%, P = 0.780) in the S-1 group than in the platinum-based CCRT group, although not statistically significant. Objective response rate (98.0% vs. 88.0%, P = 0.117) was significantly higher in the S-1 than in the platinum-based regimen, although it was not statistically reflected. Compared with platinum-based, those undergoing S-1-based chemotherapy demonstrated a higher incidence of grade 3 mucositis (20.0% vs. 2.0%, P = 0.016) in the S-1 group and a lower incidence of leukopenia (44.0% vs. 68.0%, P = 0.033), neutropenia (28.0% vs. 52.0%, P = 0.032), anemia (22.0% vs. 44.0%, P = 0.040), nephrotoxicity (4.0% vs. 20.0%, P = 0.028), and nausea/vomiting (30.0% vs. 56.0%, P = 0.019).ConclusionThe results suggest that S-1 can be used as a concurrent chemotherapy regimen during radiotherapy for patients with LANPC, since it presents a noninferior survival benefit compared with platinum and shows tolerable adverse effects.

Abstract Evidence from Europe shows that perioperative chemotherapy may be beneficial for the treatment of locally advanced gastric cancer, but reliable and robust data is lacking. To rectify this, the phase 3 RESONANCE trial investigated the efficacy and safety of S-1 plus oxaliplatin (SOX) as a perioperative chemotherapy regimen for gastric cancer. This randomized, open-label trial enrolled patients from 19 medical centers with stage II/III resectable gastric cancer who were centrally randomly assigned to either perioperative chemotherapy (PC) arm or adjuvant chemotherapy (AC) arm. Patients in the PC arm received two to four cycles of SOX followed by surgery and four to six cycles of SOX. Patients in the AC arm received upfront surgery and eight cycles of SOX. 386 patients in each group were enrolled and 756 (382 in PC and 374 in AC) were included in the mITT population. The three-year DFS rate was 61.7% in the PC arm and 53.8% in the AC arm (log-rank p = 0.019). The R0 resection rate in the PC arm was significantly higher than that in the AC arm (94.9% vs. 83.7%, p

Introduction: The multicenter randomized phase III KHBO1401 study (gemcitabine+cisplatin+S-1 [GCS] vs. GC in biliary tract cancers [BTC]) demonstrated that GCS not only prolonged patient survival but also achieved a high response rate and that it should be good for neoadjuvant therapy. Therefore, to explore the possibilities of neoadjuvant therapy, we investigated the tumor shrinkage pattern. Methods: Among the total of 246 patients enrolled in the KHBO1401, the tumor shrinkage pattern and survival were investigated in patients with measurable BTC (n = 183, 74%; GCS, n = 91; GC, n = 92). Results: The tumor shrinkage pattern could be divided into 4 categories based on the response at 100 days after enrollment: categories A (<–30% in size), B (−30–0%), C (0% to +20%), and D (>+20%). The GCS arm included more category A and B cases (61 [67%] vs. 33 [36%], p < 0.0001). Each category predicted the best response and overall survival (p < 0.0001). Category A showed sustained tumor response compared with category B; in GCS, the time to maximum tumor response was 165 ± 76 days in category A and 139 ± 78 in category B. Categories C and D did not achieve tumor shrinkage. The maximum tumor shrinkage size in category A was −53% in the GCS arm and −65% in the GC arm (p = 0.0892). Twenty percent of patients in the GCS showed tumor regrowth 154 ± 143 days later. Conclusion: GCS provided faster and greater tumor shrinkage with better survival in comparison to GC, although 20% of patients showed regrowth after 6 cycles. [ABSTRACT FROM AUTHOR]

Introduction: S-1 has been shown to be an effective adjuvant treatment option for East Asian patients who underwent gastrectomy for stage II/III gastric cancer. We conducted a phase I/II study to evaluate the feasibility, tolerability, and efficacy of administering S-1 in the adjuvant setting after R0-resection of adenocarcinoma of the stomach and esophagogastric junction (EGJ) in Caucasian patients. Methods: In this single-cohort, open-label, phase I/II trial, we enrolled patients with locally advanced adenocarcinoma of the stomach or EGJ having undergone R0-resection with or without neoadjuvant treatment. One treatment cycle consisted of oral S-1 (30 mg/m2 bid) for 14 days. Cycles were repeated every 3 weeks for 18 cycles (54 weeks). Primary endpoint was feasibility and tolerability. Safety was evaluated according to the Common Toxicity Criteria Adverse Events (CTCAE) version 4.0. Secondary endpoints were 1-year relapse-free survival (RFS) rate, RFS, and overall survival (OS). Results: Between October 2015 and February 2018, 32 patients were enrolled in 12 German centers, and 30 started adjuvant study treatment. Seventeen patients completed all 18 cycles. Two patients terminated study treatment early due to adverse events (AEs), 7 due to patient's or investigator's decision, and 4 due to recurrence or distant metastasis during adjuvant therapy. Dose levels were reduced to 25 mg/m2 in 9 patients and to 20 mg/m2 in 1 patient. Of patients completing all 18 cycles, 5 did so with reduced dosage of S-1. Documented grade ≥3 AEs were neutropenia, diarrhea, vomiting, polyneuropathy, palmar-plantar erythrodysaesthesia, and rash. Serious AEs were observed in 7 patients. Median RFS was 32.2 months. One-year RFS rate was 77%. Data on OS were still premature at the end of the study. Conclusion: Adjuvant treatment with S-1 for 1 year is a feasible and safe treatment option for Caucasian patients diagnosed with gastric adenocarcinoma or cancer of the EGJ after R0-resection. [ABSTRACT FROM AUTHOR]

Introduction: Surgical resection is considered an effective cure for biliary tract cancer (BTC); however, the prognosis is unsatisfactory despite improved surgical techniques and perioperative management. The recurrence rate remains high even after curative resection. The efficacy of adjuvant chemotherapy in pancreatic and gastric cancers has been previously reported, and the feasibility of adjuvant therapy with S-1 has recently been reported in patients with resected BTC. We aimed to retrospectively investigate the effects of adjuvant chemotherapy with S-1 on resected advanced BTC. Methods: We included data from 438 BTC patients who underwent resection between 2001 and 2020. After excluding patients with pTis-pT1 (n = 112) and other exclusion criteria, 266 patients were included in the analysis. Results: After propensity score matching, 48 patients received S-1 adjuvant chemotherapy (S-1 group), and 48 patients received non-S1 adjuvant chemotherapy or underwent surgery alone (Non-S-1 group). The patients in the S-1 group had significantly better overall survival (OS) than those in the non-S-1 group (MST 51 vs 37 months, hazard ratio [HR]:.54, 95% confidence interval [CI]:.30-.98, P =.04). The S-1 group had a significantly better recurrence-free survival (RFS) than the non-S-1 group (94 vs 21 months, HR:.57, 95% CI:.33-.97, P =.03). Subgroup analyses for OS and RFS exhibited the benefits of S-1 in patients aged <75 years and in patients with primary sites of extrahepatic and perineural invasion and curability of R0. Discussion: S-1 adjuvant therapy is promising for improving the postoperative survival of patients with resected advanced BTC, positive nerve invasion, and R0 resection. [ABSTRACT FROM AUTHOR]