Detailed analysis of metastatic colorectal cancer patients who developed cardiotoxicity on another fluoropyrimidine and switched to S-1 treatment (subgroup analysis of the CardioSwitch-study).

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.

The efficacy and safety of apatinib combined with S-1 for advanced gastric cancer: A systematic review and meta-analysis.

BACKGROUND: Advanced gastric cancer (AGC) that does not respond to first-line therapy poses a challenge to clinical management. The objective of this study was to compare the efficacy and safety of apatinib combined with S-1 in second-line and above treatment of AGC. METHODS: Cochrane Library, Science Direct, EMBASE, PubMed, and CNKI were searched for randomized controlled trial until August 2023. Only patients who met "Standardized Diagnosis and Treatment Guide for Gastric Cancer" were included in the study. The accurate data and distinguishing between follow-up time and drug dose were extracted to reduce heterogeneity and the risk of bias of the included trials was evaluated according to the Cochrane Handbook. Finally, the survival benefit of the treatment was evaluated based on clinical response rate, survival period, biochemical index, and adverse event occurrence in the trial. RESULTS: The meta-analysis included 29 randomized controlled trials involving 2149 participants. Statistically significant increases in clinical effective rate (odds ratios = 2.61, 95% confidence interval [2.13-3.20], P < .00001) and disease control rate (odds ratios = 3.16, 95% confidence interval [2.54-3.94], P < .00001) were found when apatinib combined with S-1, and also had obvious advantages in reducing tumor markers and regulating immune factors. In addition, apatinib combined with S-1 significantly increased the risk of hypertension but reduced damage to liver function, while the improvement of other adverse events was not pronounced. DISCUSSION: Apatinib combined with S-1 is more effective and safe for second-line and above treatment of AGC. This study minimized the conclusion bias caused by the basic data sources, but more high-quality studies are still needed to validate these conclusions.

Effect of Tegafur-Uracil in Resected Stage IB Lung Adenocarcinoma According to Presence or Absence of Epidermal Growth Factor Receptor Gene Mutation: A Retrospective Cohort Study.

PURPOSE: Tegafur-uracil (UFT) is the standard postoperative adjuvant therapy for stage IB lung adenocarcinoma (LUAD) in Japan. This study aimed to determine whether UFT is effective in stage IB LUAD with and without epidermal growth factor receptor (EGFR) mutations. METHODS: This retrospective study included 169 patients with stage IB LUAD who underwent complete resection at our department between 2010 and 2021. We investigated the clinicopathological and prognostic impact of EGFR mutations as well as the postoperative use of UFT. RESULTS: EGFR mutation-positive cases tended to show a higher cumulative recurrence rate than EGFR mutation-negative cases (p = 0.081), while overall survival was comparable between the groups (p = 0.238). In the entire cohort, UFT administration was not an independent prognostic factor in the multivariate regression analysis (p = 0.112). According to a stratification analysis, UFT administration was independently associated with favorable overall survival (p = 0.031) in EGFR mutation-negative cases, while it was not associated with recurrence-free survival (p = 0.991) or overall survival (p = 0.398) in EGFR mutation-positive cases. CONCLUSION: UFT administration can improve the prognosis of EGFR mutation-negative LUAD but not EGFR mutation-positive LUAD. Thus, clinical trials of adjuvant-targeted therapy for EGFR mutation-positive stage IB LUAD should also be conducted in Japan.

IgA Vasculitis as a Potential Complication of Fourth-Line Chemotherapy with Tegafur/Gimeracil/Oteracil (S-1) in Advanced Non-Small Cell Lung Cancer: A Case Report.

BACKGROUND Immunoglobulin A (IgA) vasculitis is a systemic vasculitis that involves the small vessels. It is mainly characterized by skin symptoms such as purpura, arthritis/arthralgia, abdominal symptoms, and nephropathy, which are caused by IgA adherence to the vessel walls. Herein, we report the case of an advanced non-small cell lung cancer (NSCLC) and a purpuric skin rash of the legs that developed during fourth-line chemotherapy with tegafur/gimeracil/oteracil (S-1). CASE REPORT A 68-year-old man diagnosed with NSCLC 2 years ago was undergoing S-1 as fourth-line chemotherapy when he developed purpura and edema on the lower extremities. Biopsy renal specimens were consistent with IgA vasculitis. Considering his medical history, both IgA vasculitis induced by S-1 and a paraneoplastic syndrome were considered, although the exact cause could not be identified. Subsequently, chemotherapy was discontinued because of his deteriorating general condition, and he received optimal supportive care. The purpura spontaneously disappeared; however, his ascites and renal function deteriorated. Systemic steroids improved renal function, but the ascites did not resolve. One month after being diagnosed with IgA vasculitis, the patient died due to deterioration of his general condition. CONCLUSIONS This case emphasizes the occurrence of IgA vasculitis during lung cancer treatment and its potential impact on the disease course of lung cancer. Moreover, the possible causes of IgA vasculitis in this case were paraneoplastic syndrome or S-1 adverse effects, but further case series are needed to gain a more comprehensive understanding. Refractory, steroid-unresponsive ascites may occur as an abdominal manifestation of IgA vasculitis.

Randomized phase II study of daily versus alternate-day administrations of S-1 for the elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm)-IIIA of non-small cell lung cancer: Setouchi Lung Cancer Group Study 1201.

BACKGROUND: It is shown that the postoperative adjuvant chemotherapy for non-small cell lung cancer (NSCLC) was associated with survival benefit in an elderly population. We aimed to analyze the feasibility and efficacy of alternate-day S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm) to IIIA (UICC TNM Classification of Malignant Tumours, 7th edition) NSCLC. METHODS: Elderly patients were randomly assigned to receive adjuvant chemotherapy for one year consisting of either alternate-day oral administration of S-1 (80 mg/m2/day) for 4 days a week (Arm A) or a daily oral administration of S-1 (80 mg/m2/day) for 14 consecutive days followed by 7-day rest (Arm B). The primary endpoint was feasibility (treatment completion rate), which was defined as the proportion of patients who completed the allocated intervention for 6 months with a relative dose intensity (RDI) of 70% or more. RESULTS: We enrolled 101 patients in which 97 patients received S-1 treatment. The treatment completion rate at 6 months was 69.4% in Arm A and 64.6% in Arm B (p = 0.67). Treatment completion rate in Arm B tended to be lower compared to Arm A, as the treatment period becomes longer (at 9 and 12 months). RDI of S-1 at 12 months and completion of S-1 administration without dose reduction or postponement at 12 months was significantly better in Arm A than in Arm B (p = 0.026 and p < 0.001, respectively). Among adverse events, anorexia, skin symptoms and lacrimation of any grade were significantly more frequent in Arm B compared with Arm A (p = 0.0036, 0.023 and 0.031, respectively). The 5-year recurrence-free survival rates were 56.9% and 65.7% for Arm A and B, respectively (p = 0.22). The 5-year overall survival rates were 68.6% and 82.0% for Arm A and B, respectively (p = 0.11). CONCLUSION: Although several adverse effects were less frequent in Arm A, both alternate-day and daily oral administrations of S-1 were demonstrated to be feasible in elderly patients with completely resected NSCLC. TRIAL REGISTRATION: Unique ID issued by UMIN: UMIN000007819 (Date of registration: Apr 25, 2012) https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009128. Trial ID issued by jRCT: jRCTs061180089 (Date of registration: Mar 22, 2019, for a shift toward a "specified clinical trial" based on Clinical Trials Act in Japan) https://jrct.niph.go.jp/en-latest-detail/jRCTs061180089.

Doxifluridine versus Tegafur/Gimeracil/Oteracil (S-1) as adjuvant chemotherapy for patients with gastric cancer after gastrectomy: A propensity score-matched analysis.

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.

A real-world study of anlotinib combined with GS regimen as first-line treatment for advanced pancreatic cancer.

Background: Anlotinib may boost the efficacy of pancreatic cancer (PC) treatment if timely added to the GS regimen (Gemcitabine, Tegafur-gimeracil-oteracil potassium); however, no data has been published. This study evaluated the safety and efficacy of anlotinib in combination with the GS regimen(hereafter referred to as the A+GS regimen) in the first-line treatment of patients with unresectable or metastatic PC. Methods: Patients with unresectable or metastatic PC treated at Yueyang Central Hospital and Yueyang People's Hospital between October 2018 and June 2022 were enrolled in this retrospective real-world investigation. Treatment efficacy was evaluated based on the overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and objective response rate (ORR), while the treatment safety was assessed by the frequency of major adverse events (AEs). Results: Seventy-one patients were included in this study, 41 in the GS group and 30 in the A+GS group. The A+GS group had a longer mPFS than the GS group (12.0 months (95% CI, 6.0-18.0) and 6.0 months (95% CI, 3.0-8.1)), respectively (P = 0.005). mOS was longer in the GS+A group) when compared with the GS group (17.0 months (95%CI, 14.0-20.0) and 10.0 months (95% CI, 7.5-12.5)), respectively (P = 0.018). The GS+A group had higher ORR (50.0% vs 26.8%, P = 0.045) and DCR (83.3% vs 58.5%, P = 0.026). Furthermore, there were no grade 4-5 AEs and no treatment-related deaths, and no discernible increase in AEs in the GS+A group when compared with the GS group. Conclusion: The A+GS regimen therapy holds great promise in managing treatment-naive advanced PC, except that future prospective studies with larger sample sizes and multiple centers are required to determine its efficacy and safety.

[A Case of UFT/LV-Induced Acute Liver Failure after Surgery for Sigmoid Colon Cancer].

Oral uracil and tegafur plus Leucovorin(UFT/LV)therapy is one of the standard adjuvant chemotherapies for colorectal cancer, and is widely used without any serious adverse events. Herein, we describe a case of UFT/LV-induced acute liver failure in a 75-year-old woman who underwent laparoscopic sigmoidectomy for sigmoid colon cancer. She was diagnosed with advanced colon cancer and lymph node metastasis by postoperative histopathological analysis, and adjuvant chemotherapy was initiated. After 30 days of commencing the therapy, the patient visited our hospital with complaints of severe diarrhea and difficulty in food intake. The apparent cause of these symptoms was unclear on computed tomography(CT), and mild liver damage was revealed in blood test results. The hepatic disorder gradually progressed after the hospitalization, and the condition was diagnosed as acute hepatic insufficiency. Additionally, obvious atrophy of the liver parenchyma and significant ascites were confirmed on CT. Two months later, the platelet count decreased markedly, but fortunately, no bleeding occurred. There has been no recurrence since 2 years after the surgery without any additional adjuvant therapy.

Impact of thoracic esophageal displacement after lobectomy on the continuity of oral adjuvant chemotherapy.

BACKGROUND: Adjuvant tegafur-uracil therapy has prolonged postoperative survival in patients with non-small cell lung cancer. Some patients experience treatment discontinuation due to gastrointestinal disorders such as anorexia, and the associated factors and the impact of lobectomy remain unclear. This study aimed to assess the postoperative esophageal displacement after lobectomy and to clarify its impact on the continuity of tegafur-uracil treatment. METHODS: Patients who received adjuvant tegafur-uracil therapy after lobectomy between April 2009 and March 2019 were retrospectively analyzed. Patient background, perioperative characteristics, treatment findings, and the degree of esophageal displacement measured by computed tomography were compared between the treatment completion group and the discontinuation group. A subgroup comparative analysis was further performed in the groups divided according to the degree of esophageal displacement. RESULTS: A total of 68 patients were reviewed, including 41 males and 27 females with a mean age of 66.2 years old. A total of 41 patients completed the 2-year adjuvant treatment and 27 patients discontinued it. The overall survival and relapse-free survival between the two groups were statistically significant (p = 0.027, p = 0.010). The degree of esophageal displacement at the Th7 level was a significant predictor of treatment discontinuation (p = 0.046, odds ratio [OR]: 1.138, 95% confidence interval [CI]: 1.002-1.291). Among the patients with a high degree of esophageal displacement above the baseline determined from the receiver operating characteristic curve, the cause of discontinuation was anorexia, which was significant in multivariate analysis (p = 0.013, OR: 14.72, 95% CI: 1.745-124.2). CONCLUSIONS: Our study suggested that anatomical displacement of the esophagus after lobectomy may affect the discontinuation of oral adjuvant chemotherapy in patients with lung cancer.

The clinical outcomes of combination chemotherapy in elderly patients with advanced biliary tract cancer: an exploratory analysis of JCOG1113.

In the FUGA-BT trial (JCOG1113), gemcitabine plus S-1 (GS) showed non-inferiority to gemcitabine plus cisplatin (GC) in overall survival (OS) with good tolerance for patients with advanced biliary tract cancer (BTC). We performed a subgroup analysis focused on the elderly cohort of this trial. All 354 enrolled patients in JCOG1113 were classify into two groups; < 75 (non-elderly) and ≥ 75 years (elderly) group. We investigated the influence of age on the safety analysis, including the incidence of chemotherapeutic adverse events and the efficacy analysis, including OS. There were no remarkable differences in OS between the elderly (n = 60) and the non-elderly groups (n = 294). In the elderly group, median OS was 12.7 and 17.7 months for those who received GC (n = 20) and GS (n = 40), respectively. The prevalence of all-grade adverse events was similar between the elderly and the non-elderly groups. However, among the elderly group, Grade ≥ 3 hematological adverse events were more frequently observed in the GC arm than in the GS arm. The clinical outcomes of combination chemotherapy in elderly patients with advanced BTC were comparable to non-elderly patients. GS may be the more favorable treatment for elderly patients with advanced BTC.

Fluoropyridmidine use and hypertriglyceridemia among Japanese patients: analysis of adverse event database.

Background The association between fluoropyrimidines except for capecitabine and the risk of hypertriglyceridemia is unclear. Objective To investigate hypertriglyceridemia in patients receiving fluoropyrimidines. Method This observational study used anonymized patient data recorded in the open-access Japanese Adverse Drug Event Report database. All fluoropyrimidine and taxane users were investigated. Results We identified 29,451 fluoropyrimidine users and 21,266 taxane users. Disproportionality for both hypertriglyceridemia and an increase in serum triglyceride levels was observed in fluoropyrimidine users compared with in taxane users (reporting odds ratio, 6.74; 95% confidence interval [CI] 2.05-22.17; P < .001). Multivariate logistic analysis showed that both hypertriglyceridemia and an increase in serum triglyceride levels among fluoropyrimidines users were significantly associated with doxifluridine use (odds ratio [OR] 42.50; 95% CI 5.34-338.00; P < .001), tegafur use (OR 9.56; 95% CI 2.08-43.90; P < .001), capecitabine use (OR 12.30; 95% CI 2.67-56.80; P < .001), and breast cancer (OR 5.61; 95% CI 1.07-29.50; P = .042). Conclusion This study suggests that the use of tegafur and doxifluridine is associated with an increased risk of hypertriglyceridemia similar to that with the use of capecitabine; in particular, fluoropyrimidine users with breast cancer may have a high risk of hypertriglyceridemia.

Joint Belgian recommendation on screening for DPD-deficiency in patients treated with 5-FU, capecitabine (and tegafur).

OBJECTIVES: Fluoropyrimidines such as 5-Fluorouracil (5-FU), capecitabine and tegafur are drugs that are often used in the treatment of maliginancies. The enzyme dihydropyrimidine dehydrogenase (DPD) is the first and rate limiting enzyme of 5-FU catabolism. Genetic variations within the DPYD gene (encoding for DPD protein) can lead to reduced or absent DPD activity. Treatment of DPD deficient patients with fluoropyrimidines can result in severe and, rarely, fatal toxicity. Screening for DPD deficiency should be implemented in practice. METHODS: The available methods in routine to screen for DPD deficiency were analyzed and discussed in several group meetings involving members of the oncological, genetic and toxicological societies in Belgium: targeted genotyping based on the detection of 4 DPYD variants and phenotyping, through the measurement of uracil and dihydrouracil/uracil ratio in plasma samples. RESULTS: The main advantage of targeted genotyping is the existence of prospectively validated genotype-based dosing guidelines. The main limitations of this approach are the relatively low sensitivity to detect total and partial DPD deficiency and the fact that this approach has only been validated in Caucasians so far. Phenotyping has a better sensitivity to detect total and partial DPD deficiency when performed in the correct analytical conditions and is not dependent on the ethnic origin of the patient. CONCLUSION: In Belgium, we recommend phenotype or targeted genotype testing for DPD deficiency before starting 5-FU, capecitabine or tegafur. We strongly suggest a stepwise approach using phenotype testing upfront because of the higher sensitivity and the lower cost to society.

Addition of sintilimab to nanoparticle albumin-bound paclitaxel and S-1 as adjuvant therapy in stage IIIC gastric cancer.

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

Lay abstract The prognosis of stage IIIC gastric cancer is poor and the treatment for it is not satisfying. This is a clinical trial that aims to explore a more effective therapy in gastric cancer patients of stage IIIC. Patients with stage IIIC gastric cancer must meet all of the inclusion criteria and none of the exclusion criteria to be eligible for this trial. The eligible patients will be given eight cycles of combinatory therapy of albumin-bound paclitaxel, a chemotherapy (day 1 and day 8), and S-1, another chemotherapy (days 1 to 14), plus sintilimab, a type of immunotherapy called an immune checkpoint inhibitor (day 1) every 3 weeks and then sintilimab maintenance for up to 12 months.

Application of Evidence-Based Nursing Intervention in the Treatment of Advanced Squamous Cell Carcinoma of the Lung by Erlotinib Combined with Tegafur, Gimeracil, and Oteracil Potassium and Its Influence on Quality of Life.

Objective: To explore the application of evidence-based nursing intervention in the treatment of advanced squamous cell carcinoma of the lung by erlotinib combined with tegafur, gimeracil, and oteracil potassium (TS-1) and its influence on quality of life (QOL). Methods: Clinical data of 92 patients with advanced squamous cell carcinoma of the lung treated with erlotinib and TS-1 in our hospital (January 2017-January 2021) were retrospectively analyzed. Forty-six patients receiving conventional nursing were set as the control group (CG), and other 46 patients receiving evidence-based nursing intervention additionally were set as the study group (SG). The clinical observation indexes of the two groups were compared and analyzed. Results: No obvious difference in general data between both groups (P > 0.05). According to EORTC QLQ-C30, compared with the CG, the scores of role function, physical function, social function, cognitive function, and emotional function in the SG were remarkably higher (P < 0.05). After intervention, scores of VAS of patients were obviously lower than those before intervention (P < 0.05), and scores of VAS in the SG after intervention were obviously lower than those in the CG (P < 0.05). After intervention, scores of SAS and SDS were lower than those before intervention, and those of the SG were obviously lower than those of the SG (P < 0.05). Compared with the CG, incidences of adverse reactions such as diarrhoea, nausea and vomiting, erythra, pressure sores, and leukopenia in the SG were obviously lower (P < 0.05). Compared with the CG, "very satisfied" and total satisfaction in the SG were obviously higher (P < 0.05). Conclusion: Application of evidence-based nursing intervention in the treatment of advanced squamous cell carcinoma of the lung by erlotinib combined with TS-1 can help patients to relieve pain, improve their psychological state, reduce the incidence of adverse reactions, significantly improve the QOL, and also enhance the satisfaction of clinical nursing.

Oxaliplatin plus S-1 with intraperitoneal paclitaxel for the treatment of Chinese advanced gastric cancer with peritoneal metastases.

BACKGROUND: In this study, we tried to access the efficacy and safety of oxaliplatin plus S-1 with intraperitoneal paclitaxel (PTX) for the treatment of Chinese advanced gastric cancer with peritoneal metastases. PATIENTS AND METHODS: Thirty patients diagnosed with advanced gastric cancer underwent laparoscopic exploration and were enrolled when macroscopic disseminated metastases (P1) were confirmed. PTX was diluted in 1 l of normal saline and IP administered through peritoneal port at an initial dose of 40 mg/m2 over 1 h on day1,8, respectively. Oxaliplatin was administered intravenously at an initial dose of 100 mg/m2 on day1, and S-1 was administered orally at an initial dose of 80 mg/m2 for 14 days followed by 7 days rest, repeated by every 3 weeks. RESULTS: Of all these 30 patients, the median number of cycles was 6 (range 2-16) due to the limitation of hematotoxicity and peripheral neuropathy by oxaliplatin. There were 11 (36.7%) patients received conversion surgery. The median progression free survival (PFS) was 6.6 months (95% CI = 4.7-8.5 months) and the median overall survival (OS) was 15.1 months (95% CI = 12.4-17.8 months). The grade 3-4 hematological toxicities were leucopenia (23.3%), neutropenia (23.3%), anemia (16.7%), and thrombocytopenia (20%), respectively. The grade 3-4 non-hematological toxicities were tolerated, most of which were peripheral sensory neuropathy (40%) due to oxaliplatin, diarrhea (20%), nausea and vomiting (26.7%). CONCLUSIONS: SOX+ip PTX regimen was effective in advanced gastric cancer with peritoneal metastasis. Survival time was significantly prolonged by conversion surgery. Grade 3-4 toxicities were uncommon. Large scale clinical trial is necessary to get more evidence to identify its efficacy. TRAIL REGISTRATION: ChiCTR, ChiCTR-IIR-16009802 . Registered 9 November 2016.

Phase II feasibility study of adjuvant chemotherapy with docetaxel/cisplatin/S-1 followed by S-1 for stage III gastric cancer.

BACKGROUND: This study aimed to evaluate the feasibility, safety, and efficacy of postoperative adjuvant chemotherapy with docetaxel/cisplatin/S-1 (DCS) following S-1 therapy in patients with stage III gastric cancer after curative gastrectomy. METHODS: Patients with stage III gastric cancer who underwent D2 gastrectomy were enrolled. Adjuvant chemotherapy was initiated within 8 weeks of gastrectomy. The first cycle of chemotherapy consisted of S-1 monotherapy (day 1-14), followed by a 7-day rest period. Cycles 2 and 3 consisted of the following: S-1 (day 1-14) administration, followed by a 14-day rest period, and an intravenous infusion of cisplatin and docetaxel on days 1 and 15. After two cycles, S-1 was administered for up to 1 year. RESULTS: Thirty patients were enrolled between 2014 and 2017. Febrile neutropenia of grade 3 or higher was the most common hematological toxicity with 4 patients (13.3%). Other hematological toxicities of grade 3 or higher were as follows: neutropenia in 3 (10.0%), leukopenia in 3 (10.0%), and anemia in 2 (6.7%) patients. Most frequent non-hematological toxicity of grade 3 was anorexia (n = 4, 13.3%) and general fatigue (n = 3, 10.0%); no grade 4 non-hematological toxicities were observed. Twenty-five patients (83.3%) completed two cycles of DCS treatment and 18 (60.0%) completed subsequent S-1 treatment for 1 year. The relative dose intensity of docetaxel and cisplatin was 0.86 and that of S-1 was 0.88. CONCLUSION: The DCS regimen can be acceptable as an adjuvant chemotherapy and offers an effective postoperative treatment option for stage III gastric cancer patients. TRIAL REGISTRATION NUMBER: UMIN000012785 . DATE OF REGISTRY: 08/01/2014.

Impact of Renal Function on S-1 + Radiotherapy for Locally Advanced Pancreatic Cancer: An Integrated Analysis of Data From 2 Clinical Trials.

OBJECTIVES: S-1 monotherapy with concurrent radiotherapy (RT) is a standard of care for patients with locally advanced pancreatic cancer (LAPC). Although renal dysfunction increases S-1 monotherapy toxicity, its effect in S-1 with concurrent RT remains unknown. We evaluated the effect of renal function on the safety of S-1 with RT for LAPC. METHODS: We performed an integrated exploratory post hoc analysis of data from 2 prospective studies (JCOG1106 and LAPC-S1RT), where patients with LAPC received RT (50.4 Gy/28 fraction for 5.5 weeks) and concurrent S-1 (40 mg/m2 per dose, twice daily on the day of irradiation). We split the patients into high creatinine clearance (CCr; ≥80 mL/min) and low CCr (<80 mL/min) groups and compared the findings to determine treatment safety. RESULTS: The high and low CCr groups showed a median of 97.5 (range, 80.0-194.6) and 64.4 (range, 50.0-78.3) mL/min, respectively. The low CCr group presented more adverse reactions (ARs) of grade 3 or higher and gastrointestinal ARs of grade 2 or higher than the high CCr group (30.8% vs 15.8% and 51.9% vs 36.8%). CONCLUSIONS: The incidence of ARs associated with concurrent S-1 and RT increases in patients with low CCr; therefore, ARs should be duly considered in such patients.

Survival Outcomes of Gemcitabine Plus S-1 Adjuvant Chemotherapy after Surgical Resection for Advanced Biliary Tract Cancer.

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

Severe hypertriglyceridemia induced by S-1: Subsequent case series of four patients and further review of the literature.

OBJECTIVE: We previously reported a case where S-1, containing tegafur, gimeracil, and oteracil potassium, induced severe hypertriglyceridemia. After the case, we regularly monitored serum lipid levels and surprisingly observed an additional 4 cases within 1.5 years. We here report the treatment process. CASE REPORT: At least 3 patients exhibited hyperlipidemia at baseline; in 2 of them, this was caused by previous fluoropyrimidine treatment. One patient experienced grade 4 hypertriglyceridemia, and the other 3 grade 3 hypertriglyceridemia. One patient developed temporary serum triglyceride elevation during the S-1 administration period, and the 3 experienced persistent elevation. The severity of serum triglyceride level worsened with increasing administration and peaked in cycles 2 - 6. Fenofibrate 80 - 160 mg/day and S-1 dose reduction were effective, with some significantly and others gradually decreasing to grade 0 - 1. DISCUSSION: The summarized clinical features are as follows: (1) Severe hypertriglyceridemia tends to appear after several treatment cycles and worsens with increasing administration. (2) It tends to occur in patients with hyperlipidemia at baseline. (3) Patients previously affected with fluoropyrimidines-induced hypertriglyceridemia can experience S-1 symptoms. (4) In some cases, it might decrease after the S-1 suspension period. (5) Fibrates and S-1 dose reductions were effective. As the final fluoropyrimidine product is fluorouracil, its presence or that of its metabolizing enzymes and the genetic background of the patients might have affected the results. We should be aware of the risk of temporal and asymptomatic occurrence of S-1-induced hypertriglyceridemia for early detection with appropriate treatment.

Modified FOLFIRINOX versus S-1 as second-line chemotherapy in gemcitabine-failed metastatic pancreatic cancer patients: A randomised controlled trial (MPACA-3).

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