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Medicine May 2024This study aimed to investigate the prognostic relationship between relative dose intensity (RDI) of adjuvant S-1 chemotherapy and psoas muscle mass volume (PMV) in... (Observational Study)
Observational Study
Correlation between relative dose intensity of adjuvant S-1 chemotherapy and psoas muscle mass volume and survival after resection of pancreatic ductal adenocarcinoma: A retrospective study.
This study aimed to investigate the prognostic relationship between relative dose intensity (RDI) of adjuvant S-1 chemotherapy and psoas muscle mass volume (PMV) in patients with resected pancreatic ductal adenocarcinoma. We enrolled 105 patients with histologically confirmed pancreatic ductal adenocarcinoma who had undergone pancreatectomy. Adjuvant S-1 chemotherapy was administered to 72 (68.6%) of the 105 patients and not to the remaining 33 patients. Patients who received adjuvant S-1 chemotherapy were stratified into high- and low-RDI groups by the cutoff value for RDI. Five-year overall survival (OS) and relapse-free survival (RFS) rates were significantly higher in the high- than in the low-RDI group. Similarly, both the 5-year OS and RFS rates were significantly greater among patients in the high-PMV group than among patients in the low-PMV group. The RDI was an independent prognostic factor in our study patients. Furthermore, patients who received adjuvant S-1 chemotherapy were stratified into 3 groups: those with both high RDI and high-PMV, Group A; those with either high RDI or high PMV (but not both), Group B; and those with both low RDI and low-PMV, group C. There were statistically significant differences in 5-year OS and RFS between 3 patient groups (5-year overall survival: P = .023, 5-year relapse-free survival: P = .001). The area under the curve for the combination of RDI and PMV (0.674) was greater than that for RDI alone (0.645). A sufficient dosage of adjuvant S-1 chemotherapy is important in improving survival of patients with resected pancreatic ductal adenocarcinoma. A combination of RDI and PMV may predict the prognosis of patients with resected pancreatic ductal adenocarcinoma more effective than RDI alone.
Topics: Humans; Male; Female; Oxonic Acid; Tegafur; Retrospective Studies; Middle Aged; Carcinoma, Pancreatic Ductal; Psoas Muscles; Chemotherapy, Adjuvant; Drug Combinations; Pancreatic Neoplasms; Aged; Pancreatectomy; Antimetabolites, Antineoplastic; Prognosis; Dose-Response Relationship, Drug; Adult
PubMed: 38788030
DOI: 10.1097/MD.0000000000038292 -
Medicine May 2024Advanced 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... (Meta-Analysis)
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.
Topics: Humans; Stomach Neoplasms; Oxonic Acid; Pyridines; Tegafur; Drug Combinations; Antineoplastic Combined Chemotherapy Protocols; Randomized Controlled Trials as Topic; Antineoplastic Agents; Treatment Outcome
PubMed: 38787998
DOI: 10.1097/MD.0000000000038272 -
BMC Cancer May 2024This study aims to develop a nomogram integrating inflammation (NLR), Prognostic Nutritional Index (PNI), and EBV DNA (tumor burden) to achieve personalized treatment...
OBJECTIVE
This study aims to develop a nomogram integrating inflammation (NLR), Prognostic Nutritional Index (PNI), and EBV DNA (tumor burden) to achieve personalized treatment and prediction for stage IVA NPC. Furthermore, it endeavors to pinpoint specific subgroups that may derive significant benefits from S-1 adjuvant chemotherapy.
METHODS
A total of 834 patients diagnosed with stage IVA NPC were enrolled in this study and randomly allocated into training and validation cohorts. Multivariate Cox analyses were conducted to identify independent prognostic factors for constructing the nomogram. The predictive and clinical utility of the nomogram was assessed through measures including the AUC, calibration curve, DCA, and C-indexes. IPTW was employed to balance baseline characteristics across the population. Kaplan-Meier analysis and log-rank tests were utilized to evaluate the prognostic value.
RESULTS
In our study, we examined the clinical features of 557 individuals from the training cohort and 277 from the validation cohort. The median follow-up period was 50.1 and 49.7 months, respectively. For the overall cohort, the median follow-up duration was 53.8 months. The training and validation sets showed 3-year OS rates of 87.7% and 82.5%, respectively. Meanwhile, the 3-year DMFS rates were 95.9% and 84.3%, respectively. We created a nomogram that combined PNI, NRI, and EBV DNA, resulting in high prediction accuracy. Risk stratification demonstrated substantial variations in DMFS and OS between the high and low risk groups. Patients in the high-risk group benefited significantly from the IC + CCRT + S-1 treatment. In contrast, IC + CCRT demonstrated non-inferior 3-year DMFS and OS compared to IC + CCRT + S-1 in the low-risk population, indicating the possibility of reducing treatment intensity.
CONCLUSIONS
In conclusion, our nomogram integrating NLR, PNI, and EBV DNA offers precise prognostication for stage IVA NPC. S-1 adjuvant chemotherapy provides notable benefits for high-risk patients, while treatment intensity reduction may be feasible for low-risk individuals.
Topics: Humans; Nomograms; Male; Female; Middle Aged; Nasopharyngeal Carcinoma; Chemotherapy, Adjuvant; Prognosis; Neoplasm Staging; Nasopharyngeal Neoplasms; Inflammation; Adult; Nutrition Assessment; Herpesvirus 4, Human; Tegafur; DNA, Viral; Drug Combinations; Oxonic Acid; Aged; Kaplan-Meier Estimate
PubMed: 38734620
DOI: 10.1186/s12885-024-12330-6 -
Acta Oncologica (Stockholm, Sweden) May 2024The CardioSwitch-study demonstrated that patients with solid tumors who develop cardiotoxicity on capecitabine or 5-fluorouracil (5-FU) treatment can be safely switched...
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.
Topics: Humans; Colorectal Neoplasms; Tegafur; Oxonic Acid; Male; Female; Middle Aged; Drug Combinations; Aged; Retrospective Studies; Cardiotoxicity; Capecitabine; Fluorouracil; Adult; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38698698
DOI: 10.2340/1651-226X.2024.24023 -
International Journal of Clinical... Jun 2024The aim of this study was to explore the clinical utility of serum HER2 extracellular domain (sHER2 ECD) using data from a clinical trial evaluating trastuzumab combined...
BACKGROUND
The aim of this study was to explore the clinical utility of serum HER2 extracellular domain (sHER2 ECD) using data from a clinical trial evaluating trastuzumab combined S-1 plus oxaliplatin (SOX) in HER2 positive gastric cancer.
METHODS
sHER2 ECD were prospectively measured at baseline and subsequent treatment courses. Based on each quantile point of baseline sHER2 ECD levels and its early changes, patients were divided into two groups and compared clinical outcomes.
RESULTS
43 patients were enrolled, and 17 patients (39.5%) were positive for baseline sHER2 ECD. Higher baseline sHER2 ECD levels tended to have lower hazard ratios (HRs). When divided into two groups by baseline sHER2 ECD of 19.1 ng/ml, median progression-free survival (PFS) and overall survival (OS) was longer in the higher group (mPFS: 16.8 vs 8.7 months, p = 0.359. mOS: 35.5 vs 20.6 months, p = 0.270), respectively. After initiation of treatment, sHER2 ECD significantly decreased up until the third cycle. Higher reduction rates of sHER2 ECD within 3 cycles also tended to have lower HRs. When divided into two groups by reduction rate of 42.5%, mPFS and mOS was longer in the higher reduced group (mPFS: 17.2 vs 8.7 months, p = 0.095. mOS: 65.0 vs 17.8 months, p = 0.047), respectively. Furthermore, higher reduction rates could surrogate higher objective response rates (ORR) (ORR: 90% vs 63.2% for 29.5%, p = 0.065. 100% vs 70% for 42.5%, p = 0.085), respectively.
CONCLUSIONS
Baseline sHER2 ECD levels and its early decline may be useful biomarkers for SOX plus trastuzumab efficacy in HER2 positive gastric cancer.
Topics: Humans; Stomach Neoplasms; Female; Receptor, ErbB-2; Trastuzumab; Male; Middle Aged; Oxonic Acid; Antineoplastic Combined Chemotherapy Protocols; Aged; Oxaliplatin; Tegafur; Drug Combinations; Adult; Prospective Studies; Biomarkers, Tumor; Progression-Free Survival
PubMed: 38589679
DOI: 10.1007/s10147-024-02509-z -
The American Journal of Case Reports Dec 2023BACKGROUND Immunoglobulin A (IgA) vasculitis is a systemic vasculitis that involves the small vessels. It is mainly characterized by skin symptoms such as purpura,...
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.
Topics: Male; Humans; Aged; IgA Vasculitis; Carcinoma, Non-Small-Cell Lung; Oxonic Acid; Tegafur; Ascites; Immunoglobulin A; Lung Neoplasms; Purpura; Steroids; Paraneoplastic Syndromes
PubMed: 38153915
DOI: 10.12659/AJCR.941826 -
Pharmaceutical Biology Dec 2023Thunb. (Labiatae) (CS), a perennial traditional Chinese medicinal herb that can reduce serum uric acid (sUA) levels and ameliorate renal function is widely used to...
CONTEXT
Thunb. (Labiatae) (CS), a perennial traditional Chinese medicinal herb that can reduce serum uric acid (sUA) levels and ameliorate renal function is widely used to treat hyperuricaemic nephropathy (HN).
OBJECTIVE
To investigate the molecular mechanism of action of CS in HN treatment using and experiments.
MATERIALS AND METHODS
Sprague-Dawley rats were randomly divided into control, HN, CS and positive control allopurinol groups. The HN group was intraperitoneally injected with 750 mg/kg oxonic acid potassium (OA), whereas the CS group was injected with OA along with a gavage of CS (low dose 3.125 g/kg, high dose 6.25 g/kg) for five weeks. For studies, uric acid-treated HK2 cells were used to verify the therapeutic mechanism of CS in HN.
RESULTS
HN rats exhibit pathological phenotypes of elevated sUA levels and renal injury. CS significantly improved these symptoms and sUA ( < 0.05) and blood urea nitrogen ( < 0.01) levels, and dramatically improved renal tubular injury in HN rats. The IC value of UA (uric acid) in HK2 cells was 826.32 ± 3.55 μg/mL; however, 120 ng/mL CS had no significant cytotoxicity on HK2 cells. and studies showed that CS inhibited NF-κB phosphorylation and inhibited α-smooth muscle actin (α-SMA) and vimentin expression while increasing E-cadherin expression, suggesting that CS inhibited the fibrotic process in renal cells, thus protecting renal function.
DISCUSSION AND CONCLUSIONS
These findings provide a fundamental understanding of the application of CS in HN treatment to better guide clinical interventions.
Topics: Animals; Rats; Rats, Sprague-Dawley; NF-kappa B; Hyperuricemia; Uric Acid; Epithelial-Mesenchymal Transition; Kidney
PubMed: 37599625
DOI: 10.1080/13880209.2023.2243086 -
International Journal of Molecular... Jul 2023Redox stress is involved in the aortic aneurysm pathogenesis in Marfan syndrome (MFS). We recently reported that allopurinol, a xanthine oxidoreductase inhibitor,...
Redox stress is involved in the aortic aneurysm pathogenesis in Marfan syndrome (MFS). We recently reported that allopurinol, a xanthine oxidoreductase inhibitor, blocked aortopathy in a MFS mouse model acting as an antioxidant without altering uric acid (UA) plasma levels. Hyperuricaemia is ambiguously associated with cardiovascular injuries as UA, having antioxidant or pro-oxidant properties depending on the concentration and accumulation site. We aimed to evaluate whether hyperuricaemia causes harm or relief in MFS aortopathy pathogenesis. Two-month-old male wild-type (WT) and MFS mice () were injected intraperitoneally for several weeks with potassium oxonate (PO), an inhibitor of uricase (an enzyme that catabolises UA to allantoin). Plasma UA and allantoin levels were measured via several techniques, aortic root diameter and cardiac parameters by ultrasonography, aortic wall structure by histopathology, and pNRF2 and 3-NT levels by immunofluorescence. PO induced a significant increase in UA in blood plasma both in WT and MFS mice, reaching a peak at three and four months of age but decaying at six months. Hyperuricaemic MFS mice showed no change in the characteristic aortic aneurysm progression or aortic wall disarray evidenced by large elastic laminae ruptures. There were no changes in cardiac parameters or the redox stress-induced nuclear translocation of pNRF2 in the aortic tunica media. Altogether, the results suggest that hyperuricaemia interferes neither with aortopathy nor cardiopathy in MFS mice.
Topics: Mice; Male; Animals; Marfan Syndrome; Antioxidants; Disease Models, Animal; Allantoin; Hyperuricemia; Aortic Aneurysm
PubMed: 37511051
DOI: 10.3390/ijms241411293 -
Asian Journal of Surgery Sep 2023Doxifluridine (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...
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.
Topics: Humans; Stomach Neoplasms; Tegafur; Retrospective Studies; Oxonic Acid; Propensity Score; Chemotherapy, Adjuvant; Gastrectomy; Antineoplastic Combined Chemotherapy Protocols; Neoplasm Staging
PubMed: 37002050
DOI: 10.1016/j.asjsur.2023.03.065 -
Cancer Mar 2023Based on the Japan Adjuvant Study Group of Pancreatic Cancer 01 study, the standard duration of adjuvant chemotherapy with S-1 (an oral 5-fluorouracil prodrug consisting...
Impact of S-1 adjuvant chemotherapy longer than 6 months on survival in patients with resected pancreatic cancer: a nationwide survey by the Japan Pancreas Society based on real-world data.
BACKGROUND
Based on the Japan Adjuvant Study Group of Pancreatic Cancer 01 study, the standard duration of adjuvant chemotherapy with S-1 (an oral 5-fluorouracil prodrug consisting of tegafur, gimeracil, and oteracil) in patients with resected pancreatic ductal adenocarcinoma (PDAC) was considered to be 6 months, but the impact of increasing its duration on postoperative survival was unknown. Here, the authors investigated this question by reviewing real-world data from a large cohort of patients with PDAC.
METHODS
In total, 3949 patients who underwent surgery for PDAC during the study period followed by S-1 adjuvant chemotherapy in board-certified institutions were included. Based on the duration of S-1 chemotherapy, two subgroups were defined: a standard-duration group that included patients who were treated for 180 ± 30 days and a longer duration group that included patients who received treatment for >210 days.
RESULTS
The median duration of S-1 chemotherapy was 167 days, with a mean ± standard deviation of 200 ± 193 days. After excluding patients who had a recurrence within 210 days after the initiation of adjuvant chemotherapy, postoperative recurrence-free survival (RFS) and overall survival (OS) in the standard-duration group (n = 1473) and the longer duration group (n = 975) were compared. RFS and OS did not differ significantly between the standard-duration and longer duration groups (5-year RFS: 37.8% vs. 36.2% respectively; p = .6186; 5-year OS: 52.8% vs. 53.4%, respectively; p = .5850). The insignificant difference was verified by multivariate analysis and propensity-score matching analysis.
CONCLUSIONS
The current findings suggest that extending S-1 adjuvant chemotherapy beyond 6 months has no significant additional effect on survival in patients with PDAC. This could be useful in determining whether to extend S-1 chemotherapy in patients who have completed the standard 6-month treatment.
Topics: Humans; Tegafur; Oxonic Acid; Japan; Pancreatic Neoplasms; Chemotherapy, Adjuvant; Carcinoma, Pancreatic Ductal; Pancreas; Retrospective Studies
PubMed: 36504020
DOI: 10.1002/cncr.34580