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Purpose: The high recurrence rate of colorectal cancer liver metastasis (CRCLM) after surgery remains a crucial problem. However, adjuvant chemotherapy after hepatectomy for CRCLM has not yet been established. This study evaluated the efficacy of adjuvant therapy with S-1 and oxaliplatin (SOX). Methods: In a multicenter, randomized, phase II study, patients undergoing curative resection of CRCLM were randomly enrolled in a 1:1 ratio to either the low- or high-dose group. S-1 and oxaliplatin were administered from days 1 to 14 of a 3-week cycle as a 2-h infusion every 3 weeks. The dose of S-1 was fixed at 80 mg/m2. The doses in the low- and high-dose oxaliplatin groups were 100 mg/m2 (low-dose group) and 130 mg/m2 (high-dose group), respectively. This treatment was repeated eight times. The primary endpoint was the rate of discontinuation owing to toxicity. The secondary endpoints were the relapse-free survival (RFS) and frequency of adverse events (AEs). Results: Between August 2010 and March 2015, 44 patients (low-dose group: 31 patients and high-dose group: 13 patients) were enrolled in the study. Of these, one patient was excluded from the efficacy analysis. In the high-dose group, five of nine patients were unable to continue the study due to toxicity in February 2013. At that time, recruitment to the high-dose group was stopped from the protocol. The relative dose intensity (RDI) for S-1 in the low- and high-dose groups were 49.8 and 48.7% (p = 0.712), and that for oxaliplatin was 75.9 and 73.0% (p = 0.528), respectively. The rates of discontinuation due to toxicity were 60 and 53.8% in the low- and high-dose groups, respectively, with no marked difference noted between the groups (p = 0.747). The frequency of grade ≥ 3 common adverse events was neutropenia (23.3%/23.1%), diarrhea (13.3%/15.4%), and peripheral sensory neuropathy (6.7%/7.7%). The disease-free survival (DFS) at 3 years was 52.9% in the low-dose group, which was not significantly different from that in the high-dose group (46.2%; p = 0.705). Conclusions: SOX regimens as adjuvant therapy after hepatectomy for CRCLM had high rates of discontinuation due to toxicity in both groups. In particular, the RDI of S-1 was < 50%. Therefore, the SOX regimen is not recommended as adjuvant chemotherapy after hepatectomy for CRCLM. [ABSTRACT FROM AUTHOR]

Gastric cancer rates and fatality rates have not decreased. Gastric cancer treatment has historically included surgery (both endoscopic and open), chemotherapy, targeted therapy, and immunotherapy. One of the aggravating carriers of this cancer is Helicobacter pylori infection. Various drug combinations are used to treat gastric cancer. However, examining the molecular function of these drugs, depending on whether or not there is a history of Helicobacter pylori infection, can be a better help in the treatment of these patients. This study was designed as bioinformatics. Various datasets such as patients with gastric cancer, with and without a history of H. pylori, and chemotherapy drugs cisplatin, docetaxel, and S-1 were selected. Using Venn diagrams, the similarities between gene expression profiles were assessed and isolated. Then, selected the signal pathways, ontology of candidate genes and proteins. Then, in clinical databases, we confirmed the candidate genes and proteins. The association between gastric cancer patients with and without a history of H. pylori with chemotherapy drugs was investigated. The pathways of cellular aging, apoptosis, MAPK, and TGFβ were clearly seen. After a closer look at the ontology of genes and the relationship between proteins, we nominated important biomolecules. Accordingly, NCOR1, KIT, MITF, ESF1, ARNT2, TCF7L2, and KRR1 proteins showed an important role in these connections. Finally, NCOR1, KIT, KRR1, and ESF1 proteins showed a more prominent role in the molecular mechanisms of S-1, Docetaxel, and Cisplatin in gastric cancer associated with or without H. pylori. [ABSTRACT FROM AUTHOR]

Background/Purpose: This study reports the long‐term results of a phase II trial evaluating the clinical efficacy of neoadjuvant gemcitabine, nab‐paclitaxel, and S1 (GAS) in borderline resectable pancreatic cancer with arterial contact (BRPC‐A). Methods: A multicenter, single‐arm, phase II trial was conducted. Patients received six cycles of GAS and patients without progressive disease were intended for R0 resection. Results: Of the 47 patients, 45 (96%) underwent pancreatectomy. At the time of this analysis, all patients were updated with no loss to follow‐up. A total of 30 patients died, while the remaining 17 patients were followed for a median of 68.1 months. The updated median overall survival (OS) was 41.0 months, with 2‐ and 5‐year OS rates of 68.0% and 44.6%, respectively. Multivariate analysis in the preoperative model showed that a tumor diameter reduction rate ≥10% and a CA19‐9 reduction rate ≥95% after neoadjuvant chemotherapy remained independently associated with favorable survival. In the postoperative multivariate model, no lymph node metastasis, no major surgical complications, and completion of adjuvant chemotherapy were independently associated with improved OS. Conclusions: This long‐term evaluation of the neoadjuvant GAS trial demonstrated the high efficacy of the regimen, suggesting that it is a promising treatment option for patients with BRPC‐A. [ABSTRACT FROM AUTHOR]

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 < 0.0001). There was no difference between two arms in surgical outcomes or postoperative complications. Safety-related data were like the known safety profile. In conclusion, from a clinical perspective, this trial indicated a trend towards higher three-year disease-free survival rate with perioperative SOX in stage II/III resectable gastric cancer with well-tolerated toxicity compared to adjuvant SOX, which might provide a theoretical basis for applying perioperative SOX in advanced gastric cancer patients. (ClinicalTrials.gov NCT01583361) [ABSTRACT FROM AUTHOR]

Background: The serum level of Krebs von den Lungen-6 (sKL-6) is a biomarker of interstitial pneumonia and has been reported to be elevated in patients with cancers. However, there have been few cases of gastric cancer (GC) with elevated sKL-6 that were treated by chemotherapy. We herein report two cases of GC with elevated sKL-6 that were treated with oxaliplatin plus S-1 (SOX) chemotherapy and discussed the resulting changes in sKL-6. Case presentation: The first patient was a 79-year-old woman complaining of loss of appetite. Esophagogastroduodenoscopy (EGD) showed a type-3 tumor in the gastric antrum and biopsy specimens showed adenocarcinoma. Computed tomography (CT) showed multiple liver metastases. sKL-6 was elevated to 1,292 U/ml, but a CT revealed no obvious lesions of the lungs, including interstitial pneumonia. The tumor was diagnosed as GC with liver metastases and elevated sKL-6. Respiratory function data were normal. SOX therapy using oxaliplatin and S-1 was performed. After 3 courses of SOX therapy, CT showed reductions of the liver metastases as well as the primary tumor, and sKL-6 was decreased to 201 U/ml. After the 44 courses, sKL-6 was slightly elevated. Chest CT showed interstitial pneumonia and chemotherapy was stopped. The patient is still alive without any metastasis 72 months later. The second patient was a 69-year-old woman complaining of upper abdominal pain. EGD revealed a type-3 tumor in the gastric antrum showing adenocarcinoma with HER2-positive pathology. CT showed multiple node metastases around the abdominal aorta. sKL-6 was elevated to 2,239 U/ml, but a respiratory function test showed no abnormalities, and CT of the lungs showed no obvious lesions. The tumor was diagnosed as GC with distant node metastases and elevated sKL-6. The patient received SOX therapy combined with trastuzumab. After 6 courses, the size of the primary tumor and multiple node metastases were reduced, and sKL-6 was decreased to 284 U/ml. Conclusions: These two cases suggest that sKL-6 may be important not only as an indicator of interstitial pneumonia in chemotherapeutic courses, but also as a tumor marker in GC patients with multiple metastases. [ABSTRACT FROM AUTHOR]

Background and purpose: Older patients are more likely to encounter difficulties receiving chemotherapy, but the factors involved in the continuation of chemotherapy in these patients remain unclear. We investigated the importance of muscle mass as a factor involved in delivering a sufficient dose of postoperative S-1 adjuvant chemotherapy (ACT) to older patients with gastric cancer. Methods: The subjects of this study were 79 patients aged ≥ 65 years with stage II/III gastric adenocarcinoma, who underwent curative gastrectomy and received S-1 ACT. Results: The overall median relative dose intensity (RDI) was 75.0% (18.8–93.5%). Patients were divided into two groups for receiver operating characteristic analysis according to the cutoff value. Significantly more patients in the high skeletal muscle index (SMI) group achieved > 62% RDI of S-1 ACT (p = 0.03). Conversely, more patients in the low SMI group suffered from S-1-induced nausea (p = 0.03) and discontinued chemotherapy because of adverse events (p = 0.02). Multivariate analysis identified low SMI as an independent factor for insufficient S-1 dose delivery (p = 0.03, hazard ratio = 2.87). Conclusion: Preoperative SMI is an indicator of the low-dose intensity of S-1 ACT in older patients following curative gastrectomy. [ABSTRACT FROM AUTHOR]

Summary: Background: Eribulin prolongs overall survival (OS) of patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC), particularly in later chemotherapy (ChT) treatment. However, the health-related quality of life (HRQoL) and efficacy of first or second-line therapy in eribulin-treated patients remain unknown. Using eribulin in the first- or second-line may demonstrate the non-inferiority of HRQoL compared to S-1, an oral 5-fluorouracil derivative, while maintaining OS. Methods: This randomised, controlled, open-label, phase III trial was conducted at 50 hospitals in Japan. Patients were enrolled from June 2016 and October 2019. Patients with HER2-negative MBC once under or no previous ChT were randomly assigned (1:1) to receive eribulin or S-1. HRQoL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) every six weeks until week 24 and every nine weeks until week 42. The primary endpoint was the deterioration defined as more than 10 points worsening of the general health score of QLQ-C30 or death within one year after randomisation. The secondary endpoints included OS. (Trial ID: UMIN000021398). Findings: Three hundred and two patients were enrolled, with 152 and 148 assigned to the eribulin and S-1 groups, respectively. The questionnaire compliance rate was 85.6%. Risk difference of global health status deterioration through one year was −0.66% (95% CI: −12.47–11.16; non-inferiority P = 0.077) for eribulin compared to S-1 groups. Median time to first deterioration for global health status score was 5.64 (95% CI: 3.51–8.00) and 5.28 months (95% CI: 3.28–7.80) in the eribulin and S-1 groups, respectively. The median OS was 34.7 and 27.8 months, (HR: 0.72, 95% CI: 0.54–0.96; P = 0.026); the median progression-free survival was 7.57 and 6.75 months in the eribulin and S-1 groups, (HR: 0.88, 95% CI: 0.67–1.16; P = 0.35), respectively. No new adverse events occurred. Interpretation: The time of the first clinical deterioration was similar between the two groups and OS significantly increased in eribulin-treated patients. Funding: This study was funded by CSPOR-BC and Eisai CO., Ltd.

Backgrounds: A recent randomized control trial (JCOG1202; ASCOT trial) demonstrated the efficacy of adjuvant S-1 chemotherapy (ASC) for biliary tract cancer (BTC) after surgical resection; however, the significance of the completion of ASC in the real-world setting remains unknown. Methods: Data of consecutive patients who underwent surgical resection for biliary tract cancer (BTC) from 2011 to 2021 were retrospectively reviewed. Of these, patients who underwent ASC were enrolled in this study. Patients were divided into two groups according to whether ASC was completed: the completion group and the non-completion group. Clinicopathological features and survival outcomes were assessed. Results: Of the 223 patients with BTC who underwent surgical resection, 75 patients who underwent ASC were included for analysis. Among them, 48 (64.0 %) completed the intended ASC course, while 27 cases (36.0 %) discontinued the treatment. The most common reason for the discontinuation was adverse event (n = 16, 59.3 %), followed by disease recurrence (n = 9, 33.3 %). Patients in the completion group showed significantly better overall survival (OS) (p

Abstract Aim We report the short/mid‐term results of surgery for high‐risk locally advanced rectal cancer (LARC) after neoadjuvant chemotherapy (NAC, four courses of S‐1 + oxaliplatin+ bevacizumab) without radiotherapy with the primary aim of ypT0‐2. Methods High‐risk LARC was defined as cT4b, mesorectal fascia (MRF) ≤1 mm (MRF+), or lateral lymph node metastasis (cLLN+) on high‐resolution MRI. The planned 32 cases from April 2018 to December 2021 were all included. Results There were 10 patients at cT4b (31.2%), 26 MRF+ (81.3%), and 22 cLLN+ (68.8%). Thirteen (40.6%) underwent NAC after a colostomy for stenosis. NAC was completed in 26 (81.2%) cases. Grade 3 or higher adverse events occurred in six (18.7%). One patient developed progressive disease (3.2%). Eleven were ycT0‐3MRF‐LLN‐ (34.3%). Curative‐intent surgery was performed on 31, with sphincter‐preserving surgery in 20, abdominoperineal resection in nine, total pelvic exenteration in two, and lateral lymph node dissection in 24. Two had R1/2 resection (6.4%). A Grade 3 or higher postoperative complication rate occurred in 3.2%. Pathological complete response and ypT0‐2 rates were 12.9% and 45.1%. Three‐year disease‐free survival rates (3yDFS) for ypT0‐2 and ypT ≥3 were 81.2%, 46.6% (p = 0.061), and 3‐year local recurrence rates (3yLR) were 0%, 48.8% (p = 0.015). 3yDFS for ycT0‐3MRF‐LLN‐ and ycT4/MRF+/LLN+ were 87.5%, 48.0% (p = 0.031) and 3yLR were 0%, 42.8% (p = 0.045). Conclusion NAC yielded a clinically significant effect in about half of high‐risk LARC patients. If NAC alone is ineffective, radiotherapy should be added, even if extended surgery is intended.

Abstract Purpose Gemcitabine, cisplatin, and S‐1 chemotherapy was superior to gemcitabine and cisplatin chemotherapy for progression‐free survival and overall survival for unresectable and recurrent biliary tract cancer in a randomized phase III trial (KHBO1401). This study aimed to evaluate the outcome of conversion surgery after chemotherapy in biliary tract cancer patients (ancillary study, KHBO1401‐3C). Methods A total of 246 patients were enrolled in KHBO1401. We compared progression‐free and overall survivals between the conversion surgery and non‐conversion surgery groups. Results Eight patients (3.3%) underwent conversion surgery with chemotherapy, seven of whom were diagnosed with unresectable disease and one with recurrence. Six and two patients received gemcitabine, cisplatin, and S‐1 chemotherapy as well as gemcitabine and cisplatin chemotherapy, respectively. Three patients in the conversion surgery group who received gemcitabine, cisplatin, and S‐1 chemotherapy showed no disease progression and survived without postoperative chemotherapy. Preoperative carbohydrate antigen 19‐9 (CA19‐9) level was a prognostic factor for conversion surgery. After correcting for immortal time bias, 1‐year progression‐free survival rates in the conversion surgery and non‐conversion surgery groups were 50.0% and 19.0%, respectively (hazard ratio 0.343, 95% confidence interval 0.286–0.843, p = 0.0092). One‐year overall survival rates in the conversion surgery and non‐conversion surgery groups were 87.5% and 56.0%, respectively (hazard ratio 0.222, 95% confidence interval 0.226–0.877, p = 0.0197). Conclusions Conversion surgery might be an option for the treatment of unresectable and recurrent biliary tract cancer in patients with normal preoperative CA19‐9 level.

Abstract Background We report a case of a patient with HER2-positive gastric cancer with marked tongue swelling during the second cycle of S-1, oxaliplatin, and trastuzumab. Case presentation The patient was a 74-year-old male, who was taking an angiotensin II receptor blocker (ARB) for pre-existing hypertension, with no history of allergies, diagnosed with HER2-positive gastric cancer, treated with tegafur, gimeracil, and oteracil potassium (S-1) and oxaliplatin for the first cycle, and trastuzumab was added from the second cycle. Three weeks after initiation, during an outpatient visit, grade 2 oral mucositis and significant enlargement of the patient's tongue were observed. Due to the risk of airway obstruction, the patient was referred to an otolaryngologist. After examination, hereditary angioedema was ruled out, and treatment was discontinued in view of ARB-induced angioedema. However, the tongue swelling did not improve markedly. Considering disease progression due to the discontinuation of chemotherapy, it was decided to change S-1 to capecitabine and continue treatment, and chemotherapy was resumed. Conclusions Angioedema has been reported to be hereditary and drug-related, and angiotensin-converting enzyme (ACE) inhibitors and ARBs have also been reported to lead to drug-related adverse events. Since the patient had oral mucositis at the time of onset and was taking an ARB, it is thought that oxaliplatin and S-1(SOX), and trastuzumab during ARB therapy induced oral mucositis, leading to the development of angioedema.

Lei Meng,1,&ast; Jun Cao,1,2,&ast; Li Kang,3,&ast; Gang Xu,1 Da-Wei Yuan,1 Kang Li,1 Kun Zhu1 1Department of Surgical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China; 2The Third Affiliated Hospital of Xi’an Medical University, Xi’an, 710068, People’s Republic of China; 3Department of Thoracic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kang Li; Kun Zhu, Department of Surgical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China, Tel +86 13087566643, Email healthlee@xjtu.edu.cn; dr.zhkun@mail.xjtu.edu.cnObjective: Regimens of S-1-based adjuvant chemotherapy are of great significance in attenuating recurrence risk in postoperative patients with gastric cancer (GC). Kinase insert-domain receptor (KDR) gene plays an essential role in tumor growth and metastasis. This study aimed to investigate the implication of KDR genotyping on the therapeutic outcomes of patients with gastric cancer (GC) who received S-1-based adjuvant chemotherapy.Methods: A total of 169 postoperative GC with pathological staging of II and III and no metastasis who received S-1-based adjuvant chemotherapy were included retrospectively. Peripheral blood specimens were collected and prepared for KDR genotyping and KDR mRNA expression. Correlation between KDR genotype status and prognosis was performed using Kaplan–Meier survival analysis, and multivariate analysis was ultimately adopted using Cox regression analysis.Results: Median disease-free survival (DFS) of the 169 patients with GC was 5.1 years [95% confidence interval (CI): 4.25– 5.95] and median overall survival (OS) was 6.7 years (95% CI: 5.44– 7.96). Rs2071559 was located at the upstream region, and the prevalence among 169 patients with GC was as follows: AA genotype in 104 cases (61.5%), AG genotype in 57 cases (33.7%), and GG genotype in 8 cases (4.7%), yielding a minor allele frequency of 0.22, which was consistent with Hardy-Weinberg equilibrium (P=0.958). Median DFS of patients with AA and AG/GG genotypes was 6.0 years and 4.0 years, respectively (P=0.002). Additionally, patients with the AA genotype had longer OS than those with the AG/GG genotype [median OS: not reached (NR) vs 5.5 years, P=0.011]. Additionally, KDR mRNA expression was significantly higher in patients with the AG/GG genotype than that in those with the AA genotype (P< 0.001).Conclusion: Rs2071559 in KDR gene might be a promising biomarker for evaluating the recurrence risk and OS of patients with GC who received S-1-based adjuvant chemotherapy. This conclusion should be confirmed in randomized clinical trials.Keywords: gastric cancer, S-1, KDR, polymorphism, prognosis, biomarker

Abstract Background This study evaluated the efficacy and safety of the combination chemotherapy of docetaxel plus S‐1 in patients with previously treated non‐small cell lung cancer (NSCLC) compared to docetaxel alone. Methods Patients with previously treated NSCLC were randomly assigned to docetaxel alone (arm A) or a combination of docetaxel and S‐1 (arm B) for a maximum of four cycles. The primary endpoint was overall survival (OS). Results The study was terminated early because of poor accrual. The number of patients evaluated were 74 and 77 in arm A and arm B, respectively. The median OS was 9.8 months (95% confidence interval [CI]: 6.8–15.2) and 12.3 months (95% CI: 9.2–14.5) in arms A and B, respectively. In arms A and B, the median progression‐free survival was 3.5 months (95% CI: 2.7–4.0) and 4.1 months (95% CI: 3.2–4.7), respectively. No statistically significant difference was observed in OS (hazard ratio [HR]: 0.984, 95% CI: 0.682–1.419, p = 0.4569) or progression‐free survival (HR: 0.823, 95% CI: 0.528–1.282, p = 0.0953). The major toxicity was myelosuppression. The incidence of grade 3 or more neutropenia was higher in arm A than in arm B (44.6% vs. 35.1%). However, the incidence of grade 3 or more febrile neutropenia and infection with neutropenia (12.2% vs. 22.1%) was more frequently observed in arm B. Conclusions The prematurely terminated study did not show the benefit of two cytotoxic agents over single‐agent therapy for previously treated NSCLC patients.

Objective: Gemcitabine plus nab-paclitaxel (GnP) is the standard first-line therapy for advanced pancreatic ductal adenocarcinoma (PDAC). S-1, an oral fluoropyrimidine derivative, as compared with gemcitabine, is non-inferior in terms of overall survival (OS) and is associated with lower hematologic toxicity. Accordingly, S-1 is a convenient oral alternative treatment for advanced PDAC. This study was aimed at comparing the efficacy and safety of gemcitabine plus S-1 (GS) vs. GnP as first-line chemotherapy for advanced PDAC. Methods: Patients with advanced PDAC who received first-line GS or GnP at the Peking Union Medical College Hospital between March 2011 and November 2022 were evaluated. Results: A total of 300 patients were assessed, of whom 84 received GS and 216 received GnP. The chemotherapy completion rate was higher with GS than GnP (50.0% vs. 30.3%, P = 0.0028). The objective response rate (ORR) was slightly higher (14.3% vs. 9.7%, P = 0.35), and the median OS was significantly longer (17.9 months vs. 13.3 months, P = 0.0078), in the GS group than the GnP group. However, the median progression-free survival (PFS) did not significantly differ between groups. Leukopenia risk was significantly lower in the GS group than the GnP group (14.9% vs. 28.1%, P = 0.049). Conclusions: As first-line chemotherapy for advanced PDAC, the GS regimen led to a significantly longer OS than the GnP regimen. The PFS, ORR, and incidence of severe adverse events were comparable between the GS and GnP groups.

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: Recent observations have led to an expansion of the role of neoadjuvant treatment (NAT) as a component of a multidisciplinary approach to the treatment of pancreatic ductal adenocarcinoma (PDAC). However, some issues related to this treatment remain unclear, including (1) the appropriate indications for NAT (as opposed to up-front surgery); (2) predictors of response to NAT; (3) the effect of the response to NAT on the efficacy of postoperative adjuvant chemotherapy (AC); and (4) the establishment of an adjuvant treatment policy based on post-neoadjuvant therapy/surgery histopathological findings. In this article, we discuss these issues based on a review of the literature and the authors' own experience of NAT using gemcitabine plus S-1. In addition to established evidence of the efficacy of adjuvant chemotherapy (AC) for pancreatic ductal adenocarcinoma (PDAC), evidence of the effects of neoadjuvant treatments (NATs), including chemotherapy and chemoradiotherapy, has also been accumulating. Recent results from prospective studies and meta-analyses suggest that NATs may be beneficial not only for borderline resectable PDAC, but also for resectable PDAC, by increasing the likelihood of successful R0 resection, decreasing the likelihood of the development of lymph node metastasis, and improving recurrence-free and overall survival. In addition, response to NAT may be informative for predicting the clinical course after preoperative NAT followed by surgery; in this way, the postoperative treatment strategy can be revised based on the effect of NAT and the post-neoadjuvant therapy/surgery histopathological findings. On the other hand, the response to NAT and AC is also influenced by the tumor biology and the patient's immune/nutritional status; therefore, planning of the treatment strategy and meticulous management of NAT, surgery, and AC is required on a patient-by-patient basis. Our experience of using gemcitabine plus S-1 showed that this NAT regimen achieved tumor shrinkage and decreased the levels of tumor markers but failed to provide a survival benefit. Our results also suggested that response/adverse events to NAT may be predictive of the efficacy of AC, as well as survival outcomes. [ABSTRACT FROM AUTHOR]

A recent randomized control trial (JCOG1202; ASCOT trial) demonstrated the efficacy of adjuvant S-1 chemotherapy (ASC) for biliary tract cancer (BTC) after surgical resection; however, the significance of the completion of ASC in the real-world setting remains unknown. Data of consecutive patients who underwent surgical resection for biliary tract cancer (BTC) from 2011 to 2021 were retrospectively reviewed. Of these, patients who underwent ASC were enrolled in this study. Patients were divided into two groups according to whether ASC was completed: the completion group and the non-completion group. Clinicopathological features and survival outcomes were assessed. Of the 223 patients with BTC who underwent surgical resection, 75 patients who underwent ASC were included for analysis. Among them, 48 (64.0 %) completed the intended ASC course, while 27 cases (36.0 %) discontinued the treatment. The most common reason for the discontinuation was adverse event (n = 16, 59.3 %), followed by disease recurrence (n = 9, 33.3 %). Patients in the completion group showed significantly better overall survival (OS) (p < 0.001) and recurrence-free survival (RFS) (p < 0.001) compared to the non-completion group. Further, after excluding the patients in the non-completion group who discontinued ASC due to disease recurrence, the significance of ASC completion was retained for both OS and RFS. The completion of ASC was associated with improved prognosis in patients with BTC after surgical resection. The achievement of ASC should be the goal after surgical resection, while further study may be warranted regarding the resistance of ASC. [ABSTRACT FROM AUTHOR]

Background/Aim: Renal dysfunction necessitates S-1 dose reduction. However, decreased dihydropyrimidine dehydrogenase (DPD) activity may lead to adverse events due to 5-FU. The guidelines provided by pharmaceutical companies state that total bilirubin (T-Bil) should be =upper limit of normal (ULN)×1.5 as a reference value for safely taking S-1. Nevertheless, the relationship between the degree of liver dysfunction and S-1 dose reduction has not been clearly established. Patients and Methods: This study focused on patients who received S-1 monotherapy for various types of cancer. The primary outcome was defined as the variation between blood sampling results on the test day and the subsequent test. The variation data were categorized based on the difference in T-Bil: Low T-Bil group (=2.25) and High T-Bil group (>2.25). Results: The number of patients that underwent S-1 monotherapy was 883 and the running number was 7,511; Low T-Bil group included 7,245 and High T-Bil group included 266. Examination of the effect of the T-Bil Group on clinical outcomes revealed a correlation with red blood cell (RBC) count, platelet (PLT) count, and T-Bil level. When the impact of the interaction between the T-Bil Group and any of the clinical outcomes, such as the RBC count, PLT count, and T-Bil level, was determined, each outcome showed a significant decrease in the High T-Bil group compared with the Low T-Bil group. Conclusion: S-1 administration in patients with liver dysfunction accompanied by elevated T-Bil levels may cause thrombocytopenia. [ABSTRACT FROM AUTHOR]

Background: Pancreatic adenocarcinoma carries a grim prognosis, and there are few recognized effective second-line treatment strategies. We attempted to evaluate the efficacy and safety of a combination of S-1, sintilimab, and anlotinib as a second-line treatment in pancreatic cancer patients with liver metastasis. Methods: Pancreatic cancer patients with liver metastases were recruited. S-1 was administered orally at 25 mg/m2 bid, anlotinib was administered orally at 12 mg qd from day 1 to day 14, and sintilimab was administered intravenously at 200 mg on day 1. This method was repeated every 21 days, and the therapeutic effect was evaluated every 3 cycles. The primary outcome was the objective response rate (ORR). Results: Overall, 23 patients were enrolled in this study of whom 19 patients had objective efficacy evaluation. The ORR was 10.5% (95% CI 0.4%-25.7%) in the evaluable population. The progression-free survival (PFS) was 3.53 (95% CI 2.50-7.50) months, and the overall survival (mOS) was 8.53 (95% CI 4.97-14.20) months. Grade 3 adverse events were 26.1%, and no grade 4 or above adverse events occurred. High-throughput sequencing was performed on the tumor tissues of 16 patients; patients with HRD-H (n = 10) had shorter PFS than those with HRD-L (n = 6) (2.43 vs. 5.45 months; P = 0.043), but there was no significant difference in OS between the two groups (4.43 vs. 9.35 months; P = 0.11). Conclusions: This study suggests the advantage of S-1 combined with sintilimab and anlotinib in extending OS as a second-line therapy in pancreatic cancer patients with liver metastasis. [ABSTRACT FROM AUTHOR]

Purpose: In the present study, we aimed to evaluate the efficacy and safety of camrelizumab combined with oxaliplatin plus S‐1 in patients with resectable gastric or gastroesophageal junction cancer. Methods: In this single‐arm, phase II clinical trial, patients with locally advanced gastric or gastroesophageal junction adenocarcinoma were enrolled to receive three cycles of neoadjuvant camrelizumab and oxaliplatin plus S‐1 every 3 weeks, followed by surgical resection and adjuvant therapy with the same regimen. The primary endpoint was pathological complete response (pCR) (ypT0) rate and secondary endpoints were R0 resection rate, total pCR (tpCR, ypT0N0) rate, major pathological response (MPR) rate, downstaging, objective response rate (ORR), disease control rate (DCR), event‐free survival (EFS), overall survival (OS), and safety. Results: Between September, 2020 and January, 2022, a total of 29 patients were enrolled in the present study, all of whom completed neoadjuvant therapy and underwent surgery. Three (10.3%) (95% CI: 2.2–27.4) patients achieved pCR as well as tpCR, 20 (69.0%) patients had MPR and 28 (96.6%) patients achieved R0 resection. Treatment‐emergent adverse events (AEs) of any grade were observed in 24 (82.8%) patients. Immune‐related adverse events of any grade were reported in 13 (44.8%) patients, whereas no grade 3 or higher adverse events occurred. Conclusion: The neoadjuvant therapy with camrelizumab in combination with oxaliplatin and S‐1 showed a modest pCR rate, and favorable MPR rate and safety profile in patients with gastric or gastroesophageal junction cancer. [ABSTRACT FROM AUTHOR]

Background: Although there is insufficient evidence for the treatment of older patients with advanced gastric cancer, fluorouracil combined with platinum chemotherapy has been recognized as a standard first-line treatment for such populations in Japan despite the lack of efficacy and toxicity data. Methods: Patients aged 75 years or older with advanced gastric cancer were enrolled. S-1 plus docetaxel (docetaxel: 40 mg/m2, day 1; S-1: 80 mg/m2, days 1–14; q21 days) was repeated every 3 weeks. The primary endpoint was overall response rate. Secondary endpoints were safety, progression-free survival, time to treatment failure, and overall survival. The sample size was calculated as 30 under the hypothesis of an expected response rate of 40% and a threshold response rate of 20%, at a power of 90% and a two-sided alpha value of 5%. Results: From February 2010 to January 2015, 31 patients were enrolled and assessed for efficacy and toxicity. The response rate was 45.2% (95% CI 27.3%–64.0%; p = 0.001) and it exceeded the expected response rate set at 40%. Median progression-free survival was 5.8 months, the 1-year survival rate was 58.1%, and the median survival time was 16.1 months. The major grade 3/4 adverse events were neutropenia (58%), febrile neutropenia (13%), anemia (10%), anorexia (10%), and fatigue (6%). Conclusions: These findings indicate that S-1 plus docetaxel as first-line treatment for older patients is feasible and that it has promising efficacy against advanced gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Tertiary lymphoid structures (TLSs) are observed in cancer‐invasive sites of various organs, and show evidence of tumor‐specific B and/or T cells, suggesting an active humoral antitumor response. The aim of this study was to evaluate the relationship between TLSs and prognosis in patients with tongue squamous cell carcinoma (TSCC) after preoperative S‐1 chemotherapy. Methods: Among 196 TSCC cases, 111 patients who received preoperative S‐1 chemotherapy were compared to 85 patients who did not receive chemotherapy. We investigated the incidence of TLSs in both preoperative biopsy and resected specimens. Results: TLSs were present in 24 (12%) biopsy specimens and 31 (16%) resected specimens. TLSs were associated with clinicopathologically advanced cases and positivity for lymphatic invasion. None of the cases with pStage 0 (i.e., noninvasive cancer) showed TLSs. In preoperative S‐1 chemotherapy cases, TLSs were significantly more common in those treated with S‐1 for more than 21 days and in those with treatment effects 0, Ia, and Ib. TLSs may not be a favorable prognostic factor by themselves but maybe a prognostic factor when combined with preoperative S‐1 treatment. Conclusion: The presence of TLSs was suggested to be a factor indicating a favorable prognosis when considering the indication for preoperative S‐1 chemotherapy. The synergistic effect of S‐1 by activating antitumor immunity may be associated with a better prognosis in TSCC patients with TLSs. [ABSTRACT FROM AUTHOR]

Cutaneous squamous cell carcinoma is usually treated with surgery; however, locoregionally advanced cutaneous squamous cell carcinoma can be difficult to resect. Although recent guidelines from Western countries recommend using anti–programmed cell death protein 1 (PD‐1) antibodies, including cemiplimab and pembrolizumab, there are no approved anti–PD‐1 antibodies for locoregional cutaneous squamous cell carcinoma in Asian countries. S‐1 is an oral drug with a low incidence of severe toxicity that can be used for head and neck cancers, including head and neck locoregional cutaneous squamous cell carcinoma, in Japan. We retrospectively evaluated patients with head and neck locoregional cutaneous squamous cell carcinoma treated with S‐1 at two Japanese institutions (2008–2022). The initial dosage was determined by the body surface area (<1.25 m2: 80 mg/day, 1.25–1.5 m2: 100 mg/day, ≥1.5 m2: 120 mg/day) for 28 consecutive days. The outcome measures were objective response rate (ORR), progression‐free survival (PFS), and overall survival (OS). Fourteen patients were included. The ORR was 78%, and the complete response (CR) rate was 64.3%. The median PFS and OS were not reached (NR) (95% confidence interval [CI], 5.9 months–NR) and NR (95% CI, 13.8 months–NR), respectively. The 12‐month PFS and OS rates were 51% and 85%, respectively. Six of the nine patients who achieved CR showed no recurrence during the follow‐up period (median follow‐up, 24.7 months). After CR, three patients experienced recurrence. Among these, two resumed S‐1 treatment and subsequently underwent salvage surgery, resulting in a sustained absence of recurrence. One patient developed lung metastasis and died, although S‐1 therapy was resumed. Only one patient (7.1%) developed grade 3 anemia. S‐1 showed favorable efficacy and low toxicity in patients with head and neck locoregionally advanced cutaneous squamous cell carcinoma. S‐1 may be a good alternative to the anti–PD‐1 antibody for treating head and neck locoregionally advanced squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Background: Postoperative adjuvant chemotherapy with S-1 for 1 year (corresponding to eight courses) is the standard treatment for pathological stage II gastric cancer. The phase III trial (JCOG1104) investigating the non-inferiority of four courses of S-1 to eight courses was terminated due to futility at the first interim analysis. To confirm the primary results, we reported the results after a 5-years follow-up in JCOG1104. Methods: Patients histologically diagnosed with stage II gastric cancer after radical gastrectomy were randomly assigned to receive S-1 for eight or four courses. In detail, 80 mg/m2/day S-1 was administered for 4 weeks followed by a 2-week rest as a single course. Results: Between February 16, 2012, and March 19, 2017, 590 patients were enrolled and randomly assigned to 8-course (295 patients) and 4-course (295 patients) regimens. After a 5-years follow-up, the relapse-free survival at 3 years was 92.2% for the 8-course arm and 90.1% for the 4-course arm, and that at 5 years was 87.7% for the 8-course arm and 85.6% for the 4-course arm (hazard ratio 1.265, 95% CI 0.846–1.892). The overall survival at 3 years was 94.9% for the 8-course arm, 93.2% for the 4-course arm, and that at 5 years was 89.7% for the 8-course arm, and 88.6% for the 4-course arm (HR 1.121, 95% CI 0.719–1.749). Conclusions: The survival of the four-course arm was slightly but consistently inferior to that of the eight-course arm. Eight-course S-1 should thus remain the standard adjuvant chemotherapy for pathological stage II gastric cancer. [ABSTRACT FROM AUTHOR]

Background and purpose: The CardioSwitch-study demonstrated that patients with solid tumors who develop cardiotoxicity on capecitabine or 5-fluorouracil (5-FU) treatment can be safely switched to S-1, an alternative fluoropyrimidine (FP). In light of the European Medicines Agency approval of S-1 in metastatic colorectal cancer (mCRC), this analysis provides more detailed safety and efficacy information, and data regarding metastasectomy and/or local ablative therapy (LAT), on the mCRC patients from the original study. Materials and methods: This retrospective cohort study was conducted at 12 European centers. The primary endpoint was recurrence of cardiotoxicity after switch. For this analysis, safety data are reported for 78 mCRC patients from the CardioSwitch cohort (N = 200). Detailed efficacy and outcomes data were available for 66 mCRC patients. Results: Data for the safety of S-1 in mCRC patients were similar to the original CardioSwitch cohort and that expected for FP-based treatment, with no new concerns. Recurrent cardiotoxicity (all grade 1) with S-1-based treatment occurred in 4/78 (5%) mCRC patients; all were able to complete FP treatment. Median progression-free survival from initiation of S-1-based treatment was 9.0 months and median overall survival 26.7 months. Metastasectomy and/or LAT was performed in 33/66 (50%) patients, and S-1 was successfully used in recommended neoadjuvant/conversion or adjuvant-like combination regimens and schedules as for standard FPs. Interpretation: S-1 is a safe and effective FP alternative when mCRC patients are forced to discontinue 5-FU or capecitabine due to cardiotoxicity and can be safely used in the standard recommended regimens, settings, and schedules. [ABSTRACT FROM AUTHOR]

Aim: We report the short/mid‐term results of surgery for high‐risk locally advanced rectal cancer (LARC) after neoadjuvant chemotherapy (NAC, four courses of S‐1 + oxaliplatin+ bevacizumab) without radiotherapy with the primary aim of ypT0‐2. Methods: High‐risk LARC was defined as cT4b, mesorectal fascia (MRF) ≤1 mm (MRF+), or lateral lymph node metastasis (cLLN+) on high‐resolution MRI. The planned 32 cases from April 2018 to December 2021 were all included. Results: There were 10 patients at cT4b (31.2%), 26 MRF+ (81.3%), and 22 cLLN+ (68.8%). Thirteen (40.6%) underwent NAC after a colostomy for stenosis. NAC was completed in 26 (81.2%) cases. Grade 3 or higher adverse events occurred in six (18.7%). One patient developed progressive disease (3.2%). Eleven were ycT0‐3MRF‐LLN‐ (34.3%). Curative‐intent surgery was performed on 31, with sphincter‐preserving surgery in 20, abdominoperineal resection in nine, total pelvic exenteration in two, and lateral lymph node dissection in 24. Two had R1/2 resection (6.4%). A Grade 3 or higher postoperative complication rate occurred in 3.2%. Pathological complete response and ypT0‐2 rates were 12.9% and 45.1%. Three‐year disease‐free survival rates (3yDFS) for ypT0‐2 and ypT ≥3 were 81.2%, 46.6% (p = 0.061), and 3‐year local recurrence rates (3yLR) were 0%, 48.8% (p = 0.015). 3yDFS for ycT0‐3MRF‐LLN‐ and ycT4/MRF+/LLN+ were 87.5%, 48.0% (p = 0.031) and 3yLR were 0%, 42.8% (p = 0.045). Conclusion: NAC yielded a clinically significant effect in about half of high‐risk LARC patients. If NAC alone is ineffective, radiotherapy should be added, even if extended surgery is intended. [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. [ABSTRACT FROM AUTHOR]

Background Recent studies suggest that early tumor shrinkage (ETS) and depth of response (DpR) reflect outcomes of chemotherapy in various cancers. This study evaluated the association of ETS and DpR with clinical outcomes using data from JCOG1113, which demonstrated the non-inferiority of gemcitabine plus S-1 (GS) to gemcitabine plus cisplatin (GC) for chemotherapy-naïve advanced biliary tract cancer. Material and Methods In total, 354 (289 with measurable target lesions) patients enrolled in JCOG1113 were divided into ETS-unachieved and ETS-achieved groups (≥20% tumor reduction at week 6) and DpR-low and DpR-high groups (≥40% maximum shrinkage) until 12 weeks after enrollment. The impact of ETS and DpR on survival outcome was evaluated using the multivariable Cox proportional hazard model. Results The proportions of patients in the ETS-achieved and DpR-high groups were similar between the 2 treatment arms. The hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS) for the ETS-achieved group were 0.70 (95% confidence interval (CI), 0.52-0.93) and 0.60 (95%CI, 0.44-0.81), respectively. The HRs of PFS and OS for the DpR-high group were 0.67 (95%CI, 0.48-0.94) and 0.64 (95%CI, 0.46-0.90), respectively. In the subpopulation treatment effect pattern plot analysis, most patients in the ETS-achieved group in the GC arm did not experience disease progression after 12 weeks from the landmark. Conclusion As on-treatment markers, ETS and DpR were effective tools. ETS was clinically useful, because it can be used to evaluate the outcomes of treatment early at a specific time. [ABSTRACT FROM AUTHOR]

Purpose: The intensity of adjuvant treatment for pancreatic ductal adenocarcinomas (PDACs) has not been stratified according to the risk after resection. This study was designed to identify patients with PDACs in whom the current S-1 adjuvant treatment is ineffective. Methods: This single-center, retrospective study included patients who underwent pancreatectomy for PDACs from 2009 to 2020 at Sendai Open Hospital and were receiving S-1 adjuvant treatment. The independent risk factors for recurrence and survival were determined by using a Cox proportional hazards regression model. The effects of S-1 adjuvant treatment and detailed patterns of recurrence were evaluated in patients with high-risk factors. Results: Overall, 118 patients with PDAC received S-1 adjuvant treatment. Postoperative nonnormalized carbohydrate antigen (CA19-9) was a predictive risk factor for recurrence (p < 0.010; hazard ratio [HR], 3.87; 95% confidence interval [CI], 2.26–6.62) and survival (p = 0.008; HR, 2.25; 95% CI, 1.24–4.11) after S-1 adjuvant treatment. In 24 patients with nonnormalized postoperative CA19-9, S-1 monotherapy was ineffective in preventing recurrence, even during the treatment period, compared with that noted in patients who did not receive adjuvant treatment. The recurrence rate during adjuvant treatment was 41.7%; in all cases, recurrence was caused by distant metastasis. The total recurrence rate was up to 95.8%, and distant recurrence was especially frequent. Conclusions: The current S-1 adjuvant treatment regimen is ineffective for patients with postoperative nonnormalized CA19-9. The postoperative CA19-9 level may be a good indicator for further aggressive treatment. This study may lead to further discussions on intensity stratification of adjuvant treatments for PDAC. [ABSTRACT FROM AUTHOR]

Introduction: Doxifluridine (DF), an oral 5-FU prodrug, has been used for various solid cancers due to its efficacy and low toxicity. We aim to evaluate the effect of DF as adjuvant monotherapy in advanced gastric cancer. Methods: We retrospectively reviewed the clinical data of 263 patients with advanced gastric cancer who underwent curative gastrectomy between January 2010 and December 2013 at our institute. Since previous randomized control trials have confirmed the efficacy of S-1 as adjuvant chemotherapy in advanced gastric cancer, we analyzed the oncologic effect and patient compliance of the DF group compared to the S-1 group. After propensity score matching, 48 patients were included in each group. Results: There was no significant difference in 5-year overall survival (OS) and 5-year disease-free survival (DFS) between DF and S-1 groups (5-year OS; 77.1% vs 75.0%; p = 0.729, 5-year DFS; 76.6% vs 73.9%; p = 0.748). The completion rates of the DF and S-1 groups were 60.4% and 72.9%, respectively (p = 0.194). The mean relative dose intensity of the DF and S-1 groups were 76.2% and 84.2%, respectively (p = 0.195). After multivariate analysis, the chemotherapy regimen was not a risk factor for OS and DFS, whereas relative dose intensity and pathologic stage were independent prognostic factors. Conclusion: There was no significant difference in the oncologic effect and patient compliance between DF and S-1 groups. DF could be an alternative option for adjuvant chemotherapy in advanced gastric cancer. In addition, we confirmed that relative dose intensity is an important independent prognostic factor for survival.

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).

BackgroundPancreatic adenocarcinoma carries a grim prognosis, and there are few recognized effective second-line treatment strategies. We attempted to evaluate the efficacy and safety of a combination of S-1, sintilimab, and anlotinib as a second-line treatment in pancreatic cancer patients with liver metastasis.MethodsPancreatic cancer patients with liver metastases were recruited. S-1 was administered orally at 25 mg/m2 bid, anlotinib was administered orally at 12 mg qd from day 1 to day 14, and sintilimab was administered intravenously at 200 mg on day 1. This method was repeated every 21 days, and the therapeutic effect was evaluated every 3 cycles. The primary outcome was the objective response rate (ORR).ResultsOverall, 23 patients were enrolled in this study of whom 19 patients had objective efficacy evaluation. The ORR was 10.5% (95% CI 0.4%–25.7%) in the evaluable population. The progression-free survival (PFS) was 3.53 (95% CI 2.50–7.50) months, and the overall survival (mOS) was 8.53 (95% CI 4.97–14.20) months. Grade 3 adverse events were 26.1%, and no grade 4 or above adverse events occurred. High-throughput sequencing was performed on the tumor tissues of 16 patients; patients with HRD-H (n = 10) had shorter PFS than those with HRD-L (n = 6) (2.43 vs. 5.45 months; P = 0.043), but there was no significant difference in OS between the two groups (4.43 vs. 9.35 months; P = 0.11).ConclusionsThis study suggests the advantage of S-1 combined with sintilimab and anlotinib in extending OS as a second-line therapy in pancreatic cancer patients with liver metastasis.Clinical Trial Registration: ChiCTR2000030659

Background: We report a case of a patient with HER2-positive gastric cancer with marked tongue swelling during the second cycle of S-1, oxaliplatin, and trastuzumab. Case presentation: The patient was a 74-year-old male, who was taking an angiotensin II receptor blocker (ARB) for pre-existing hypertension, with no history of allergies, diagnosed with HER2-positive gastric cancer, treated with tegafur, gimeracil, and oteracil potassium (S-1) and oxaliplatin for the first cycle, and trastuzumab was added from the second cycle. Three weeks after initiation, during an outpatient visit, grade 2 oral mucositis and significant enlargement of the patient's tongue were observed. Due to the risk of airway obstruction, the patient was referred to an otolaryngologist. After examination, hereditary angioedema was ruled out, and treatment was discontinued in view of ARB-induced angioedema. However, the tongue swelling did not improve markedly. Considering disease progression due to the discontinuation of chemotherapy, it was decided to change S-1 to capecitabine and continue treatment, and chemotherapy was resumed. Conclusions: Angioedema has been reported to be hereditary and drug-related, and angiotensin-converting enzyme (ACE) inhibitors and ARBs have also been reported to lead to drug-related adverse events. Since the patient had oral mucositis at the time of onset and was taking an ARB, it is thought that oxaliplatin and S-1(SOX), and trastuzumab during ARB therapy induced oral mucositis, leading to the development of angioedema. [ABSTRACT FROM AUTHOR]

Purpose: A phase III trial comparing S-1 and docetaxel with S-1 alone as postoperative chemotherapy for pathologically Stage III gastric cancer was conducted and clarified the superiority of the doublet in terms of 3-year relapse-free survival as the primary endpoint (67.7% versus 57.4%, hazard ratio [HR] 0.715, 95% confidence interval [CI] 0.587–0.871; p = 0.0008). This final report analyzed 5-year survival outcomes along with the incidence and pattern of late recurrences. Patients and methods: Patients with histologically confirmed Stage III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive adjuvant chemotherapy with either S-1 plus docetaxel or S-1 alone. The same 912 patients who were evaluated for 3-year survival outcomes in the previous report were analyzed. Results: Five-year overall survival rate of the S-1 plus docetaxel group (67.91%) was significantly superior to that in the S-1 group (60.27%; HR 0.752, 95% CI 0.613–0.922; p = 0.0059). The incidence of late recurrence at > 3 years after randomization was similar in both groups (7.3% versus 7.2%). Peritoneal dissemination was the most common pattern of late recurrence. Addition of docetaxel significantly suppressed relapse through the lymphatic (6.8% [95% CI 4.52–9.17] versus 15% [95% CI 11.76–18.30]; p < 0.0001) and hematogenous (10.2% [95% CI 7.37–12.94] versus 15.7% [95% CI 12.36–19.01]; p < 0.0137) pathways throughout the 5 years of follow-up. Conclusion: The survival benefit of postoperative chemotherapy with S-1 and docetaxel in terms of 5-year overall survival rate was confirmed for patients with pathologically Stage III gastric cancer, although late recurrences were not prevented. [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]

Purpose: Gemcitabine, cisplatin, and S‐1 chemotherapy was superior to gemcitabine and cisplatin chemotherapy for progression‐free survival and overall survival for unresectable and recurrent biliary tract cancer in a randomized phase III trial (KHBO1401). This study aimed to evaluate the outcome of conversion surgery after chemotherapy in biliary tract cancer patients (ancillary study, KHBO1401‐3C). Methods: A total of 246 patients were enrolled in KHBO1401. We compared progression‐free and overall survivals between the conversion surgery and non‐conversion surgery groups. Results: Eight patients (3.3%) underwent conversion surgery with chemotherapy, seven of whom were diagnosed with unresectable disease and one with recurrence. Six and two patients received gemcitabine, cisplatin, and S‐1 chemotherapy as well as gemcitabine and cisplatin chemotherapy, respectively. Three patients in the conversion surgery group who received gemcitabine, cisplatin, and S‐1 chemotherapy showed no disease progression and survived without postoperative chemotherapy. Preoperative carbohydrate antigen 19‐9 (CA19‐9) level was a prognostic factor for conversion surgery. After correcting for immortal time bias, 1‐year progression‐free survival rates in the conversion surgery and non‐conversion surgery groups were 50.0% and 19.0%, respectively (hazard ratio 0.343, 95% confidence interval 0.286–0.843, p = 0.0092). One‐year overall survival rates in the conversion surgery and non‐conversion surgery groups were 87.5% and 56.0%, respectively (hazard ratio 0.222, 95% confidence interval 0.226–0.877, p = 0.0197). Conclusions: Conversion surgery might be an option for the treatment of unresectable and recurrent biliary tract cancer in patients with normal preoperative CA19‐9 level. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the efficacy and safety of the combination chemotherapy of docetaxel plus S‐1 in patients with previously treated non‐small cell lung cancer (NSCLC) compared to docetaxel alone. Methods: Patients with previously treated NSCLC were randomly assigned to docetaxel alone (arm A) or a combination of docetaxel and S‐1 (arm B) for a maximum of four cycles. The primary endpoint was overall survival (OS). Results: The study was terminated early because of poor accrual. The number of patients evaluated were 74 and 77 in arm A and arm B, respectively. The median OS was 9.8 months (95% confidence interval [CI]: 6.8–15.2) and 12.3 months (95% CI: 9.2–14.5) in arms A and B, respectively. In arms A and B, the median progression‐free survival was 3.5 months (95% CI: 2.7–4.0) and 4.1 months (95% CI: 3.2–4.7), respectively. No statistically significant difference was observed in OS (hazard ratio [HR]: 0.984, 95% CI: 0.682–1.419, p = 0.4569) or progression‐free survival (HR: 0.823, 95% CI: 0.528–1.282, p = 0.0953). The major toxicity was myelosuppression. The incidence of grade 3 or more neutropenia was higher in arm A than in arm B (44.6% vs. 35.1%). However, the incidence of grade 3 or more febrile neutropenia and infection with neutropenia (12.2% vs. 22.1%) was more frequently observed in arm B. Conclusions: The prematurely terminated study did not show the benefit of two cytotoxic agents over single‐agent therapy for previously treated NSCLC patients. [ABSTRACT FROM AUTHOR]

Purpose: Poorly cohesive cells-gastric cancer (PCC-GC) represents distinct features within the GC spectrum. The present study investigated the clinicopathologic characteristics and chemo-sensitivity for a relatively large cohort of PCC-GC patients. Materials and methods: A total of 268 patients diagnosed with stage II or III PCC-GC were included. GC cell lines were also analyzed for drug sensitivity to 5-fluorouracil (5-FU) and oxaliplatin in vitro. Results: One hundred fifteen (42.9%) patients were stage II and 153 (57.1%) were stage III. Two hundred twenty-three (83.2%) patients received adjuvant therapy. Among these patients, 139 (62.3%) received CAPOX and 84 (37.7%) received S-1. With a median follow-up of 38.9 (1.6–137.8) months, the estimated 5-year disease-free survival (DFS) and overall survival (OS) rates were 52.3% and 61.0%, respectively. In the univariate analysis, survival was significantly better in the adjuvant chemotherapy group than in the surgery only group. In the subgroup analysis, there was no significant difference in DFS or OS between the types of adjuvant chemotherapy for either disease stage. In vitro cell line analysis, different responses to 5-FU and oxaliplatin were observed in SRC and non-SRC, where the treatment in KATOIII cell lines with oxaliplatin had less effect at a higher concentration compared to non-SRC cell lines. Conclusion: The current study found that adjuvant chemotherapy was not significantly associated with survival benefit for patients with resected stage II and III PCC-GC. Plus, S-1 showed numerically longer DFS and OS compared to CAPOX in PCC-GC patients, although no significant in the multivariate analysis. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to evaluate the efficacy and safety of docetaxel/S-1 (TS) compared with docetaxel/capecitabine (TX) as a first-line treatment for advanced breast cancer. Methods: Patients with advanced metastatic breast cancer were randomly divided into the TS group (n = 54) and the TX group (n = 57) for first-line chemotherapy from August 2015 to April 2019 (ClinicalTrials.org registration no. NCT02947061). Following the completion of combination therapy, patients without progression received S-1 or capecitabine maintenance treatment. The primary end point was progression-free survival (PFS). Results: Among 111 enrolled patients, the median PFS did not differ significantly between the TS group and the TX group (TS vs. TX, 9.0 vs. 7.4 months, P = 0.365, 95% confidence interval [CI]: 0.50–1.11, hazard ratio [HR]: 0.75). There was also no statistically significant difference in median overall survival (OS) between the two groups (TS vs. TX, 40.2 vs. 41.3 months, P = 0.976). In addition, visceral metastasis and metastasis sites, such as the liver or lung, did not lead to a significant effect on PFS and OS. The two regimens showed no significant difference in adverse events, except hand-foot syndrome, which predominated in the TX group (38.6% vs. 7.4%, P = 0.001), and diarrhea (24.1% vs. 3.6%, P = 0.003) and elevation of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels (14.8% vs. 3.5%, P = 0.049), which were more frequent in the TS group. Conclusions: The TS and TX regimens demonstrated similar efficacy and safety for the first-line treatment of advanced breast cancer. The TS regimen had fewer cases of severe hand-foot syndrome than the TX regimen, representing an effective alternative option to the TX regimen. Further studies are warranted to define the efficacy and safety of this strategy in real-world settings.

Abstract Background and Objective In general, there are not many studies exploring the clinical value of adjuvant chemotherapy or maintenance chemotherapy (AC/MC) after induction chemotherapy and concurrent chemoradiotherapy (IC+CCRT+AC/MC). The purpose of this study was to establish a clinical nomogram for the use of AC/MC in patients with locoregionally advanced nasopharyngeal carcinoma (LA‐NPC). Material and Methods Two centers (Guangzhou Medical University Cancer Center [N = 1226] and Zhongshan People's Hospital [N = 150]) recruited 1376 patients with LA‐NPC. All the patients underwent IC+CCRT; 560 patients received AC with cisplatin/nedaplatin plus docetaxel/paclitaxel (TP) or cisplatin/nedaplatin plus fluorouracil (PF), and 81 patients received MC with S‐1. Multivariate Cox regression was used to confirm optimal predictors of progression‐free survival (PFS), and a nomogram was established to identify patients into low‐risk and high‐risk cohorts. Additionally, bootstrap internal validation was performed to further verify our nomogram. Results After propensity score matching (PSM), the survival curves were not statistically different between IC+CCRT+AC/MC and IC+CCRT (all p > 0.05). Then, a nomogram was developed based on variables that were screened by univariate and multivariate Cox regression, including N stage, cumulative platinum dose during CCRT, body mass index (BMI), IC cycles, IC regimen and cervical lymph node (CLN) necrosis and infiltration of adjacent tissues. The results of the nomogram showed that the high‐risk cohort had greatly worse 5‐year DMFS, LRFS, PFS and OS compared to low‐risk cohort (all p

Abstract Background The role of adjuvant chemotherapy in patients with pathological lymph node‐positive (pN+) resectable esophageal squamous cell carcinoma (ESCC) remains unclear. We aimed to explore whether adjuvant chemotherapy could improve the overall survival (OS) of patients with pN+ ESCC and whether oral chemotherapy could be used as an alternative to intravenous chemotherapy. Methods The patients were divided into two groups: a surgery plus chemotherapy group (S + CT group, 400 patients) and a surgery alone group (S group, 582 patients). Propensity score matching (PSM) was used to create patient groups that were balanced across several covariates (n = 331 in each group). The survival rates of patients receiving oral chemotherapy (69 patients with S‐1 and 68 patients with tegafur tablets) and intravenous chemotherapy (263 patients) were compared using the Kaplan–Meier method. Results In the overall study cohort, the 3‐year OS was significantly higher in the S + CT group than in the S group (66.3% vs. 49.9%, p

Abstract Background Intraperitoneal paclitaxel is proved to be efficient for peritoneal metastasis of gastric cancer. It remains uncertain the efficacy and safety of the triplets regimen which combined intraperitoneal high‐dose paclitaxel with systemic SOX in gastric cancer patients with peritoneal metastasis. This study aimed to evaluate the efficacy and safety of intraperitoneal administration of high‐dose paclitaxel, intravenous oxaliplatin and S‐1 in patients with peritoneal metastatic gastric cancer. Methods This single‐center, prospective, single‐arm phase II study was conducted between January 2017 and May 2019 in West China Hospital, Sichuan University. Patients diagnosed with primary gastric cancer by histopathology and confirmed synchronous peritoneal metastasis were enrolled. This study aimed to evaluate efficacy and safety of intraperitoneal administration of high‐dose paclitaxel (80 mg/m2, d1), intravenous oxaliplatin (100 mg/m2, d1), and S‐1 (80 mg/m2, d1‐14) of patients. The primary endpoint was 1‐year overall survival rate, and the second endpoints were progression‐free survival (PFS), overall survival (OS), overall response rate (ORR), disease control rate (DCR) and adverse events. Results In this single‐arm phase II clinical trial, 49 patients received SOX combined intraperitoneal high‐dose paclitaxel treatment. One‐year survival rate was 81.6% (95% CI, 68.6–90.0%). Median PFS and OS were 6.50 months (95% CI, 2.89–10.11) and 16.9 months (95% CI, 13.58 to 20.22), respectively; ORR was 55.3% (95% CI, 41.3–68.6) and DCR was 76.6% (95% CI, 62.8–86.4). Thirteen patients underwent second laparoscopic detection, but only nine ultimately underwent radical gastrectomy. Subgroup analysis showed that sPCI ≤12 was a good index for a favorable prognosis. The most frequent grade 3/4 toxicities were neutropenia (40.8%), anemia (22.4%), leukopenia (18.4%), nausea (14.3%), and vomiting (12.2%). None of the patients had any intraperitoneal catheter‐related complications. Conclusions Intraperitoneal high‐dose paclitaxel with systemic SOX is an effective and tolerable first‐line treatment for patients with peritoneal metastatic gastric cancer and patients with sPCI≤12 scores might be recommended crowd for this regimen as conversion therapy.

Abstract Purpose The prognosis of diffuse‐type gastric cancer (DGC) is poorer than that of intestinal type, but S‐1 is a potential treatment option in DGC. This study explored the maximal tolerated dose (MTD) and the recommended dose for phase II study (RP2D) of nab‐paclitaxel combined with S‐1 (AS regimen) as adjuvant chemotherapy in stage III DGC. Methods Patients with stage III DGC were recruited into this phase I dose‐escalation study between July 2019 and June 2020 in Zhongshan Hospital. Nab‐paclitaxel and S‐1 (80–120 mg/day, d1‐14, q3w) were administrated for 6 cycles, and then 8 cycles of S‐1 monotherapy were applied. The patients received nab‐paclitaxel at 180, 220, or 260 mg/m2 according to the 3 + 3 design based on dose‐limiting toxicity (DLT). The primary endpoint was RP2D. Secondary endpoints were the 1‐year disease‐free survival (DFS) rate and adverse events (AEs). Results One case experienced DLT in 180‐mg/m2 dose group, subsequently three additional subjects were enrolled. DLT was not observed in the 220‐ and 260‐mg/m2 dose groups (both n = 3). Therefore, the MTD has not reached, and the RP2D of nab‐paclitaxel would be 260 mg/m2. Five participants showed progressive disease, with three and two participants in the 180‐ and 220‐mg/m2 dose groups, respectively. The 6‐, 12‐, and 18‐month DFS rates were 100%, 63.6%, and 50.9%, respectively. The most frequently observed AEs were neutropenia (83.3%) and leukopenia (66.7%). Conclusion The RP2D of nab‐paclitaxel as adjuvant chemotherapy in DGC was 260 mg/m2. The AS regimen had a tolerable AE profile in stage III DGC.

Background: S-1 plus docetaxel (DS) therapy followed by S-1 is the standard of care in Japan in postoperative adjuvant chemotherapy for stage III gastric cancer, but long-term survival and the number of DS cycles required are unclear. The purpose of this study was to investigate the impact of the number of cycles of DS therapy on the 5-year survival in stage III gastric cancer in a pooled analysis of two phase II trials (OGSG0604 and OGSG1002). Patients and methods: Patients with histologically confirmed stage III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were enrolled in this pooled analysis. They received DS therapy for four or eight cycles, followed by S-1 until 1 year postgastrectomy. The 5-year overall survival (OS) and the 5-year disease free survival (DFS) by the landmark analysis was evaluated. Results: In total, 113 patients from the OGSG0604 and OGSG1002 trials were enrolled in this study. The landmark analysis showed a 5-year OS that was better with four to eight cycles of DS therapy than with one to three cycles of DS therapy, with the best 5-year OS of 77.4% (95% confidence interval, 66.5–90.1%) for eight cycles. The 5-year DFS was approximately 66% when four or eight cycles of DS therapy were given. Conclusion: Although eight cycles of DS therapy may prolong prognosis, the present study did not provide a clear conclusion as to how many DS therapy cycles are needed to improve prognosis after D2 gastrectomy for stage III gastric cancer. Trial registration: Registration number: UMIN00000714 and UMIN000004440. [ABSTRACT FROM AUTHOR]

Background: The development of triplet regimens for advanced gastric cancer is challenging. The aim of this phase I dose-escalation study was to determine the maximum tolerated dose and recommended dose of the combination of irinotecan, cisplatin, and S-1 in chemotherapy-naïve patients with HER2-negative advanced gastric cancer. Methods: The 3 + 3 design was adopted. Every 4 weeks, patients received an escalating dose of intravenous irinotecan (100–150 mg/m2) on day 1 and fixed doses of intravenous cisplatin (60 mg/m2) on day 1 and oral S-1 (80 mg/m2) on days 1 to 14. Results: Twelve patients were enrolled in two dose level cohorts. In the level 1 cohort (irinotecan 100 mg/m2, cisplatin 60 mg/m2, and S-1 80 mg/m2), dose-limiting toxicity including grade 4 neutropenia and febrile neutropenia occurred in one of six patients, whereas in the level 2 cohort (irinotecan 125 mg/m2, cisplatin 60 mg/m2, and S-1 80 mg/m2), dose-limiting toxicities including grade 4 neutropenia developed in two of six patients. Thus, the level 1 and 2 doses were determined to be the recommended and maximum tolerated doses, respectively. Common grade 3 or higher adverse events were neutropenia (75%; n = 9), anemia (25%; n = 3), anorexia (8%; n = 1), and febrile neutropenia (17%; n = 2). Irinotecan, cisplatin, and S-1 combination therapy achieved an overall response rate of 67% with a median progression-free survival and overall survival of 19.3 and 22.4 months, respectively. Conclusions: The potential treatment efficacy of this triplet regimen in HER2-negative advanced gastric cancer warrants further evaluation, especially in patients requiring intensive chemotherapy. [ABSTRACT FROM AUTHOR]

Doxifluridine (DF), an oral 5-FU prodrug, has been used for various solid cancers due to its efficacy and low toxicity. We aim to evaluate the effect of DF as adjuvant monotherapy in advanced gastric cancer. We retrospectively reviewed the clinical data of 263 patients with advanced gastric cancer who underwent curative gastrectomy between January 2010 and December 2013 at our institute. Since previous randomized control trials have confirmed the efficacy of S-1 as adjuvant chemotherapy in advanced gastric cancer, we analyzed the oncologic effect and patient compliance of the DF group compared to the S-1 group. After propensity score matching, 48 patients were included in each group. There was no significant difference in 5-year overall survival (OS) and 5-year disease-free survival (DFS) between DF and S-1 groups (5-year OS; 77.1% vs 75.0%; p = 0.729, 5-year DFS; 76.6% vs 73.9%; p = 0.748). The completion rates of the DF and S-1 groups were 60.4% and 72.9%, respectively (p = 0.194). The mean relative dose intensity of the DF and S-1 groups were 76.2% and 84.2%, respectively (p = 0.195). After multivariate analysis, the chemotherapy regimen was not a risk factor for OS and DFS, whereas relative dose intensity and pathologic stage were independent prognostic factors. There was no significant difference in the oncologic effect and patient compliance between DF and S-1 groups. DF could be an alternative option for adjuvant chemotherapy in advanced gastric cancer. In addition, we confirmed that relative dose intensity is an important independent prognostic factor for survival. [ABSTRACT FROM AUTHOR]

Background: Based on the Japan Adjuvant Study Group of Pancreatic Cancer-01 results, S-1 adjuvant chemotherapy has been the standard in resected pancreatic ductal adenocarcinoma (PDAC) patients in Japan and elsewhere, initiated within 10 weeks after surgery. To assess the clinical impact of this timing, we conducted a secondary analysis of a nationwide survey by the Japan Pancreas Society. Methods: A total of 3361 patients were divided into two groups: 2681 (79.8%) initiating the therapy within 10 weeks after surgery (standard) and 680 (20.2%) after 10 weeks (delayed). We compared recurrence-free survival (RFS) and overall survival (OS) using the log-rank test and Cox proportional hazards model with conditional landmark analysis between the groups. Results were verified by adjustment with inverse-probability-of-treatment weighting (IPTW) analysis. Results: The median timing of S-1 adjuvant chemotherapy initiation was 50 days (interquartile range: 38–66). In the standard group, 5-year RFS and OS rates were 32.3–48.7%, respectively, compared with 25.0–38.7% in the delayed group. Hazard ratios (HRs) and 95% confidence intervals were 0.84 (0.76–0.93) for RFS (p < 0.001) and 0.77 (0.69–0.87) for OS (p < 0.001). The IPTW analysis yielded 5-year RFS rates of 32.1% and 25.3% in the standard versus delayed group, respectively [HR = 0.86 (0.77–0.96), p < 0.001] and 5-year OS rates of 48.3% and 39.8%, respectively [HR = 0.81 (0.71–0.92), p < 0.001]. Conclusions: Initiation of S-1 adjuvant chemotherapy in resected PDAC patients within 10 weeks after surgery may offer survival benefit over later initiation. [ABSTRACT FROM AUTHOR]

The safety and effectiveness of chemotherapy in elderly patients with biliary tract cancer (BTC) remain unclear. Therefore, we retrospectively reviewed patients who underwent chemotherapy for locally advanced, metastatic, or recurrent BTC at our institution from January 2016 to December 2021. Of the 283 included patients, 91 (32.5%) were aged 75 years or older when initiating chemotherapy. Elderly patients were more likely than non-elderly patients to receive monotherapy with gemcitabine or S-1 (58.7% vs. 9.4%, p < 0.001) and were less likely to experience grade 3–4 toxicities (55.4% vs. 70.2%, p = 0.015). The rates of termination due to intolerance (6.5% vs. 5.8%, p = 0.800) and transition to second-line chemotherapy (39.1% vs. 40.3%, p = 0.849) were similar between groups. In the overall cohort, age was not an independent predictor of overall survival (OS). Within the elderly cohort, there were no differences in severe adverse events between patients receiving monotherapy and combination therapy (50.0% vs. 63.2%, p = 0.211). Median OS was longer in the combination therapy group (10.4 vs. 14.1 months; p = 0.010); however, choice of monotherapy was not an independent predictor of overall survival. Monotherapy appears to be a viable alternative in selected elderly BTC patients. [ABSTRACT FROM AUTHOR]

Objectives: Preoperative S-1 chemotherapy is administered to prevent tumor proliferation before surgery in oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the relationship between the histological therapeutic effect and prognosis in patients with OSCC after pre-operative S-1 chemotherapy. Materials and methods: Among 461 OSCC cases, 281 patients who received preoperative S-1 chemotherapy were compared with 180 patients that did not receive chemotherapy to determine the histological therapeutic effect in the resected specimens and the differences in relapse-free survival. Results: The histological chemotherapeutic effect was well correlated with the subsequent prognosis. In an examination of the combined effect of treatment and ypStage, the groups with good S-1 treatment effects had extremely good prognoses, even if the postoperative resection specimens were within the same ypStage. In a stratified search of patients who received S-1 for more than 7 days and who had a significantly better prognosis than those who did not receive S-1, it was found that the prognosis was significantly better for patients with tongue cancer according to site; furthermore, tongue cancer, age under 70 years of age, male sex, and clinical stage I were factors associated with a significantly better prognosis. Conclusions: Even if the postoperative resection specimens were within the same ypStage, the groups that responded to S-1 treatment were considered to have extremely good prognoses. Clinical relevance: A good adaptation for S-1 was tongue cancer, and especially tongue cancer with cStage I, male sex, and age less than 70 years old. [ABSTRACT FROM AUTHOR]

Background: Definitive chemoradiotherapy (CRT) with 5-fluorouracil plus mitomycin-C is a standard treatment for stage II/III squamous cell carcinoma of the anal canal (SCCA). We performed this dose-finding and single-arm confirmatory trial of CRT with S-1 plus mitomycin-C to determine the recommended dose (RD) of S-1 and evaluate its efficacy and safety for locally advanced SCCA. Methods: Patients with clinical stage II/III SCCA (UICC 6th) received CRT comprising mitomycin-C (10 mg/m2 on days 1 and 29) and S-1 (60 mg/m2/day at level 0 and 80 mg/m2/day at level 1 on days 1–14 and 29–42) with concurrent radiotherapy (59.4 Gy). Dose-finding used a 3 + 3 cohort design. The primary endpoint of the confirmatory trial was 3-year event-free survival. The sample size was 65, with one-sided alpha of 5%, power of 80%, and expected and threshold values of 75% and 60%, respectively. Results: Sixty-nine patients (dose-finding, n = 10; confirmatory, n = 59) were enrolled. The RD of S-1 was determined as 80 mg/m2/day. Three-year event-free survival in 63 eligible patients who received the RD was 65.0% (90% confidence interval 54.1–73.9). Three-year overall, progression-free, and colostomy-free survival rates were 87.3%, 85.7%, and 76.2%, respectively; the complete response rate was 81% on central review. Common grade 3/4 acute toxicities were leukopenia (63.1%), neutropenia (40.0%), diarrhea (20.0%), radiation dermatitis (15.4%), and febrile neutropenia (3.1%). No treatment-related deaths occurred. Conclusions: Although the primary endpoint was not met, S-1/mitomycin-C chemoradiotherapy had an acceptable toxicity profile and favorable 3-year survival and could be a treatment option for locally advanced SCCA. Clinical trial information: jRCTs031180002. [ABSTRACT FROM AUTHOR]