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Journal of B.U.ON. : Official Journal... 2016To assess the efficacy and safety of S-1 plus sorafenib for the treatment of advanced hepatocellular carcinoma (HCC). (Review)
Review
PURPOSE
To assess the efficacy and safety of S-1 plus sorafenib for the treatment of advanced hepatocellular carcinoma (HCC).
METHODS
PubMed, the Cochrane Library, EMBASE, and ClinicalTrials.gov were searched using the terms "Hepatocellular Carcinoma" or "HCC" or "Hepatoma" or "Liver cancer" and "S-1" and "Sorafenib" or "Nexavar". Outcomes of main interest included overall survival (OS) and toxicities.
RESULTS
We identified 2 studies of S"1 plus sorafenib from 77 references that included a total of 65 patients. The percentage of male patients ranged from 70.0 to 89.5%. Median age was 59.2 years and ranged from 48.0 to 65.5 years. The percentage of hepatitis B virus ranged from 23.1 to 90.0%. The recommended dose of S-1 and sorafenib was 80 or 64 mg/m/day and 800 mg/day, respectively and treatment was administered orally on days 1-14 and days 1-21, respectively. Median OS were 10.4 and 10.5 months, respectively. The incidence of all-grade toxicities of more than 30% were hand"foot syndrome (HFS) and rash. The incidence of grade 3/4 toxicities more than 5% were thrombocytopenia, elevated AST/ALT and hyperbilirubinemia.
CONCLUSION
This systematic review suggests that S-1 plus sorafenib showed modest clinical efficacy and tolerable toxicity profile in patients with advanced HCC. The recommended dose of S-1 and sorafenib was 80 or 64 mg/m/day and 800 mg/day, respectively.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Disease Progression; Disease-Free Survival; Drug Combinations; Female; Humans; Liver Neoplasms; Male; Middle Aged; Niacinamide; Oxonic Acid; Phenylurea Compounds; Protein Kinase Inhibitors; Sorafenib; Tegafur; Time Factors; Treatment Outcome
PubMed: 28039697
DOI: No ID Found -
Medicine Apr 2021Advanced gastric cancer (AGC) patients are not tolerant to the toxicities of traditional chemotherapy and its second-line therapeutic regimens are limited. The aim of...
Advanced gastric cancer (AGC) patients are not tolerant to the toxicities of traditional chemotherapy and its second-line therapeutic regimens are limited. The aim of the present study is to evaluate the efficacy and safety of apatinib combined with S-1 as the second-line therapy for AGC patients.Patients with AGC were enrolled in this study. Patients received oral apatinib (250 mg to 500 mg once daily) and S-1(40 mg/m2 twice daily) on days 1-14. Each cycle was 28 days and one course of treatment consisted of 2 cycles. Clinical efficacy and adverse events (AEs) were observed. Kaplan-Meier method was used for survival analysis.From November 2015 to December 2017, 58 AGC patients who failed first-line chemotherapy were enrolled and assessed retrospectively. According to the Response Evaluation Criteria in Solid Tumors (RECIST) standard, all patients were evaluable for response. None achieved CR, and 10 (17.2%) achieved PR (95% CI 7.2%-27.3%). SD was observed in 58.6% (34/58) of patients (95% CI 45.6%-71.7%) and NR in 24.1% (14/58) of patients (95% CI 12.8%-35.5%). The objective response rate (ORR) and the disease control rate (DCR) were 17.2% and 75.8% respectively. The median progression-free survival (PFS) and median overall survival (OS) were 143.1 days (95% CI 121.7-164.5) and 211.6 days (95% CI 162.9-219.7) respectively. The multivariate analysis showed that the ECOG PS was the independent factor of PFS and OS for AGC patients (PFS: HR = 3.565, 95% CI: 2.25-5.65, P < .001; OS: HR = 3.676, 95% CI: 2.29-5.89, P < .001). The main AEs were fatigue (72.4%), hypertension (46.6%), and leukopenia (48.3%).Apatinib combined with S-1 showed promising efficiency and was well tolerated as the second-line therapy for AGC patients. ECOG PS was the independent factor of PFS and OS for AGC patients. AEs were moderate and controllable, and leukopenia or hypertension was predictable factors for the PFS and OS of AGC patients.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Drug Therapy, Combination; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Oxonic Acid; Progression-Free Survival; Pyridines; Response Evaluation Criteria in Solid Tumors; Retrospective Studies; Stomach Neoplasms; Tegafur; Young Adult
PubMed: 33907117
DOI: 10.1097/MD.0000000000025630 -
Medicine Oct 2018To investigate the treatment effects of gemcitabine plus S-1 (GS) for metastatic pancreatic cancer in our institution.Data from 41 patients with metastatic pancreatic... (Observational Study)
Observational Study
To investigate the treatment effects of gemcitabine plus S-1 (GS) for metastatic pancreatic cancer in our institution.Data from 41 patients with metastatic pancreatic cancer treated with GS regimen in West China Hospital, Sichuan University were reviewed. The therapeutic efficacy and toxicity were evaluated. The influencing factors of progression-free survival (PFS) and overall survival (OS) were also explored.At the last follow-up, all patients had died. The objective response rate was 22.0% (9/41) and the disease control rate was 65.9% (27/41). The median PFS and OS times were 5.1 (range, 1.5-21) and 10.6 months (range, 1.5-40), respectively. The 0.5-, 1-, and 2-year OS rates were 65.9%, 41.5%, and 9.8%, respectively. In multivariate analysis, body mass index and carbohydrate antigen 19-9 change were the significant influencing factors of PFS, compared to tumor site and chemotherapy cycles for OS. The adverse effects were moderate and tolerable.The effects of GS for metastatic pancreatic cancer in our institution were good. The adverse effects were moderate and tolerable. However, further investigation in future prospective clinical studies is warranted.
Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; China; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Pancreatic Neoplasms; Prospective Studies; Tegafur; Gemcitabine
PubMed: 30313120
DOI: 10.1097/MD.0000000000012836 -
Nutrients Sep 2021Hyperuricemia is the primary cause of gouty arthritis and other metabolic disorders. Eggshell membrane (EM) is an effective and safe supplement for curing pain and...
Hyperuricemia is the primary cause of gouty arthritis and other metabolic disorders. Eggshell membrane (EM) is an effective and safe supplement for curing pain and stiffness connected with osteoarthritis. However, the effect of EM on hyperuricemia is unclear. This study determines the effects of EM on potassium oxonate-injected hyperuricemia. Uric acid, creatinine, blood urea nitrogen concentrations in the serum, and xanthine oxidase activity in the liver are measured. Protein levels of renal urate transporter 1 (URAT1), organic anion transporters 1 (OAT1), glucose transporter 9 (GLUT9), and ATP-binding cassette transporter G2 (ABCG2) in the kidney are determined with renal histopathology. The results demonstrate that EM reduces serum uric acid levels and increases urine uric acid levels in hyperuricemic rats. Moreover, EM downregulates renal URAT1 protein expression, upregulates OAT1 and ABCG2, but does not change GLUT9 expression. Additionally, EM does not change xanthine oxidase activity in the liver or the serum. EM also decreases uric acid uptake into oocytes expressing hURAT1. Finally, EM markedly reduces renal inflammation and serum interleukin-1β levels. These findings suggest that EM exhibits antihyperuricemic effects by promoting renal urate excretion and regulating renal urate transporters. Therefore, EM may be useful in the prevention and treatment of gout and hyperuricemia.
Topics: Animals; Egg Shell; Humans; Hyperuricemia; Inflammation; Injections; Kidney; Kidney Function Tests; Male; Oocytes; Organic Anion Transporters; Oxonic Acid; Rats, Sprague-Dawley; Uric Acid; Xanthine Oxidase; Xenopus; Rats
PubMed: 34684325
DOI: 10.3390/nu13103323 -
The Journal of Biological Chemistry Mar 1955
Topics: Allantoin; Humans; Hydantoins; Oxidation-Reduction; Oxonic Acid; Uric Acid
PubMed: 14353937
DOI: No ID Found -
World Journal of Gastroenterology Jan 2014To assess the efficacy and safety of combination therapy based on S-1, a novel oral fluoropyrimidine, vs S-1 monotherapy in advanced gastric cancer (AGC). (Meta-Analysis)
Meta-Analysis Review
AIM
To assess the efficacy and safety of combination therapy based on S-1, a novel oral fluoropyrimidine, vs S-1 monotherapy in advanced gastric cancer (AGC).
METHODS
We searched PubMed, EMBASE and the Cochrane Library for eligible studies published before March 2013. Our analysis identified four randomized controlled trials involving 790 participants with AGC. The outcome measures were overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and grade 3-4 adverse events.
RESULTS
Meta-analysis showed that S-1-based combination therapy significantly improved OS (HR = 0.77, 95%CI: 0.66-0.91, P = 0.002), PFS (HR = 0.58, 95%CI: 0.46-0.72, P = 0.000) and ORR (OR = 2.23, 95%CI: 1.54-3.21, P = 0.000). Sensitivity analysis further confirmed this association. Lower incidence of grade 3-4 leucopenia (OR = 4.06, 95%CI: 2.11-7.81), neutropenia (OR = 3.94, 95%CI: 2.1-7.81) and diarrhea (OR = 2.41, 95%CI: 1.31-4.44) was observed in patients with S-1 monotherapy.
CONCLUSION
S-1-based combination therapy is superior to S-1 monotherapy in terms of OS, PFS and ORR. S-1 monotherapy is associated with less toxicity.
Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Disease-Free Survival; Drug Combinations; Humans; Odds Ratio; Oxonic Acid; Risk Factors; Stomach Neoplasms; Tegafur; Time Factors; Treatment Outcome
PubMed: 24415887
DOI: 10.3748/wjg.v20.i1.310 -
Oncology (Williston Park, N.Y.) Oct 1998Discussed herein are selected oral fluorinated pyrimidines that are converted to 5-fluorouracil (5-FU) in vivo to exert antitumor activity. These agents include... (Review)
Review
Discussed herein are selected oral fluorinated pyrimidines that are converted to 5-fluorouracil (5-FU) in vivo to exert antitumor activity. These agents include capecitabine (Xeloda), tegafur-uracil (UFT) plus leucovorin (Orzel), and S-1 (BMS247616). These agents offer the convenience of an orally administered therapy with potentially fewer toxic effects than conventional bolus regimens of 5-FU plus leucovorin. These oral agents provide prolonged 5-FU exposure at lower peak concentrations than observed with bolus intravenous administration of 5-FU and may confer pharmacoeconomic advantages by reducing administration costs and toxicity-related hospitalizations. These regimens also have the potential for improved therapeutic activity by achieving higher 5-FU concentrations in the tumor or by biochemically modulating 5-FU. Phase III trials in patients with advanced colorectal carcinomas are comparing the antitumor activity of these agents with that of intravenous 5-FU plus leucovorin.
Topics: Administration, Oral; Antimetabolites, Antineoplastic; Capecitabine; Deoxycytidine; Fluorouracil; Humans; Leucovorin; Oxonic Acid; Prodrugs; Pyridines; Tegafur; Uracil
PubMed: 9830626
DOI: No ID Found -
Biomedical and Environmental Sciences :... Dec 2015We tested whether melamine nephrotoxicity was exacerbated by urate (a typical component of renal stones in humans) in rats with hyperuricemiainduced by the uricase...
OBJECTIVE
We tested whether melamine nephrotoxicity was exacerbated by urate (a typical component of renal stones in humans) in rats with hyperuricemiainduced by the uricase inhibitor, potassium oxonate (Oxo).
METHODS
Rats were exposed to melamine or Oxo alone or combinations of melamine (200-400 mg/kg) and Oxo (200-600 mg/kg) for 3 consecutive days. Kidney injury was evaluated by renal biochemical functions, histomorphology, and lipid peroxidation. Kidney crystals were analyzed for their composition.
RESULTS
Nephrotoxicity was minimal in animals administered melamine or Oxo alone, but it was demonstrable in animals administered at least 800 mg/kg of the two compounds combined. All rats in the 400+600 (melamine+Oxo) and 400+400 mg/kg groups and 4 out of 6 in the 200+600 mg/kg group died within 3 days; no rat died in the 200+400 or 200+200 mg/kg group. Dose-dependent renal damage resembling clinical findings in affected patients was observed in rats administered the two compounds. Crystal composition determination revealed the existence of melamine and uric acid in the affected kidneys, resembling human stones.
CONCLUSION
Our findings suggest that uric acid plays a key role in melamine-related kidney injury in humans. Future studies should consider uric acid together with melamine when examining adverse effects in humans.
Topics: Animals; Disease Models, Animal; Hyperuricemia; Kidney Diseases; Lipid Peroxidation; Male; Oxonic Acid; Rats, Wistar; Triazines
PubMed: 26777910
DOI: 10.3967/bes2015.124 -
World Journal of Gastroenterology Apr 2015To rationally evaluate the effect of S-1 vs capecitabine for the treatment of gastric cancer. (Meta-Analysis)
Meta-Analysis Review
AIM
To rationally evaluate the effect of S-1 vs capecitabine for the treatment of gastric cancer.
METHODS
MEDLINE, EMBASE, Cochrane Controlled Trials Register, Google Scholar, and China Journal Full Text Database were accessed to collect clinical randomized controlled trials regarding the effect of S-1 vs capecitabine for the treatment of gastric cancer patients. Statistical analysis was performed by meta-analysis. Four randomized controlled trials met the inclusion criteria.
RESULTS
Compared with capecitabine regimens, the 1-year survival rate in gastric cancer patients was 0.80 (95%CI: 0.52-1.21, P = 0.29). The overall response rate of S-1 vs capecitabine was 0.94 (95%CI: 0.59-1.51, P = 0.93). Compared with capecitabine regimens, the most frequent hematologic toxicities were neutropenia (OR = 0.99, 95%CI: 0.65-1.49, P = 0.94) and thrombocytopenia (OR = 0.72, 95%CI: 0.31-1.67, P = 0.44). The most frequent non-hematologic toxicities included nausea (OR = 0.85, 95%CI: 0.56-1.28, P = 0.43) and hand-foot syndrome (OR = 0.16, 95%CI: 0.10-0.27, P < 0.00001).
CONCLUSION
The existing studies suggest that S-1 is not more effective than capecitabine in the treatment of gastric cancer patients, but does exhibit less toxicity with regard to hand-foot syndrome.
Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chi-Square Distribution; Drug Combinations; Hand-Foot Syndrome; Humans; Odds Ratio; Oxonic Acid; Risk Factors; Stomach Neoplasms; Survival Analysis; Survival Rate; Tegafur; Time Factors; Treatment Outcome
PubMed: 25892887
DOI: 10.3748/wjg.v21.i14.4358 -
Medicine Jul 2017Pancreatic cancer (PC) is one of the most lethal digestive system tumors. Most new cases are diagnosed based on metastasis or local aggression and are known as "advanced... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Pancreatic cancer (PC) is one of the most lethal digestive system tumors. Most new cases are diagnosed based on metastasis or local aggression and are known as "advanced PC." Recently, studies investigating S-1 have indicated that it has a better clinical curative effect on PC. We conducted a meta-analysis to evaluate the efficacy and safety of S-1 monotherapy compared with S-1 combination regimens in patients with gemcitabine (GEM)-refractory PC.
METHODS
Trials published between 1978 and 2016 were identified by an electronic search of public databases (Medline, Embase, and the Cochrane Library). All prospective studies were independently identified by 2 authors for inclusion. The response rate (RR), progression-free and overall survival (PFS and OS, respectively), and the primary toxicities were extracted for the meta-analysis.
RESULTS
Four randomized controlled trials consisting of 623 patients were included in the analysis, among which 315 patients underwent S-1 monotherapy and 308 patients underwent S-1 combination therapy. The pooled data showed a significantly higher response rate and longer PFS in the S-1 combination group than in the S-1 monotherapy group (RR, 1.75; 95% confidence interval [CI], 1.19-2.57; P = .005 and hazard ration [HR], 0.75; 95% CI, 0.62-0.91; P = .005). There were no significant differences in OS or adverse events.
CONCLUSIONS
Compared with the S-1 monotherapy group, the S-1 combination group had a higher response rate and longer PFS. Both groups had few adverse events, which were balanced between the groups. The subgroup analysis suggested that S-1 combination regimens with leucovorin or irinotecan (CPT-11) provided promising efficacy. These promising combination regimens should be considered for patients with advanced PC who choose S-1 as their second-line therapy.
Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Combinations; Drug Resistance, Neoplasm; Humans; Oxonic Acid; Pancreatic Neoplasms; Randomized Controlled Trials as Topic; Tegafur; Gemcitabine
PubMed: 28746215
DOI: 10.1097/MD.0000000000007611