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The New England Journal of Medicine Apr 2004In a previous phase 3 trial of adjuvant chemotherapy after resection of non-small-cell lung cancer, a combination of uracil and tegafur (often referred to as UFT) taken... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
In a previous phase 3 trial of adjuvant chemotherapy after resection of non-small-cell lung cancer, a combination of uracil and tegafur (often referred to as UFT) taken orally was shown to prolong survival. A subgroup analysis disclosed that most patients who benefited had pathological stage I adenocarcinoma.
METHODS
We randomly assigned patients with completely resected pathological stage I adenocarcinoma of the lung to receive either oral uracil-tegafur (250 mg of tegafur per square meter of body-surface area per day) for two years or no treatment. Randomization was performed with stratification according to the pathological tumor category (T1 vs. T2), sex, and age. The primary end point was overall survival.
RESULTS
From January 1994 through March 1997, 999 patients were enrolled. Twenty patients were found to be ineligible and were excluded from the analysis after randomization; 491 patients were assigned to receive uracil-tegafur and 488 were assigned to observation. The median duration of follow-up for surviving patients was 73 months. The difference in overall survival between the two groups was statistically significant in favor of the uracil-tegafur group (P=0.04 by a stratified log-rank test). Grade 3 toxic effects occurred in 10 of the 482 patients (2 percent) who actually received uracil-tegafur.
CONCLUSIONS
Adjuvant chemotherapy with uracil-tegafur improves survival among patients with completely resected pathological stage I adenocarcinoma of the lung.
Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Patient Compliance; Prodrugs; Proportional Hazards Models; Survival Analysis; Tegafur; Treatment Failure; Uracil
PubMed: 15102997
DOI: 10.1056/NEJMoa032792 -
Annals of Oncology : Official Journal... Jan 2015We evaluated the efficacy and safety of S-1 plus oxaliplatin (SOX) as an alternative to cisplatin plus S-1 (CS) in first-line chemotherapy for advanced gastric cancer... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
We evaluated the efficacy and safety of S-1 plus oxaliplatin (SOX) as an alternative to cisplatin plus S-1 (CS) in first-line chemotherapy for advanced gastric cancer (AGC).
PATIENTS AND METHODS
In this randomized, open-label, multicenter phase III study, patients were randomly assigned to receive SOX (80-120 mg/day S-1 for 2 weeks with 100 mg/m(2) oxaliplatin on day 1, every 3 weeks) or CS (S-1 for 3 weeks with 60 mg/m(2) cisplatin on day 8, every 5 weeks). The primary end points were noninferiority in progression-free survival (PFS) and relative efficacy in overall survival (OS) for SOX using adjusted hazard ratios (HRs) with stratification factors; performance status and unresectable or recurrent (+adjuvant chemotherapy) disease.
RESULTS
Overall, 685 patients were randomized from January 2010 to October 2011. In per-protocol population, SOX (n = 318) was noninferior to CS (n = 324) in PFS [median, 5.5 versus 5.4 months; HR 1.004, 95% confidence interval (CI) 0.840-1.199; predefined noninferiority margin 1.30]. The median OS for SOX and CS were 14.1 and 13.1 months, respectively (HR 0.958 with 95% CI 0.803-1.142). In the intention-to-treat population (SOX, n = 339; CS, n = 337), the HRs in PFS and OS were 0.979 (95% CI 0.821-1.167) and 0.934 (95% CI 0.786-1.108), respectively. The most common ≥grade 3 adverse events (SOX versus CS) were neutropenia (19.5% versus 41.8%), anemia (15.1% versus 32.5%), hyponatremia (4.4% versus 13.4%), febrile neutropenia (0.9% versus 6.9%), and sensory neuropathy (4.7% versus 0%).
CONCLUSION
SOX is as effective as CS for AGC with favorable safety profile, therefore SOX can replace CS.
CLINICAL TRIAL NUMBER
JapicCTI-101021.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur; Young Adult
PubMed: 25316259
DOI: 10.1093/annonc/mdu472 -
The New England Journal of Medicine Nov 2007Advanced gastric cancer can respond to S-1, an oral fluoropyrimidine. We tested S-1 as adjuvant chemotherapy in patients with curatively resected gastric cancer. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Advanced gastric cancer can respond to S-1, an oral fluoropyrimidine. We tested S-1 as adjuvant chemotherapy in patients with curatively resected gastric cancer.
METHODS
Patients in Japan with stage II or III gastric cancer who underwent gastrectomy with extended (D2) lymph-node dissection were randomly assigned to undergo surgery followed by adjuvant therapy with S-1 or to undergo surgery only. In the S-1 group, administration of S-1 was started within 6 weeks after surgery and continued for 1 year. The treatment regimen consisted of 6-week cycles in which, in principle, 80 mg of oral S-1 per square meter of body-surface area per day was given for 4 weeks and no chemotherapy was given for the following 2 weeks. The primary end point was overall survival.
RESULTS
We randomly assigned 529 patients to the S-1 group and 530 patients to the surgery-only group between October 2001 and December 2004. The trial was stopped on the recommendation of the independent data and safety monitoring committee, because the first interim analysis, performed 1 year after enrollment was completed, showed that the S-1 group had a higher rate of overall survival than the surgery-only group (P=0.002). Analysis of follow-up data showed that the 3-year overall survival rate was 80.1% in the S-1 group and 70.1% in the surgery-only group. The hazard ratio for death in the S-1 group, as compared with the surgery-only group, was 0.68 (95% confidence interval, 0.52 to 0.87; P=0.003). Adverse events of grade 3 or grade 4 (defined according to the Common Toxicity Criteria of the National Cancer Institute) that were relatively common in the S-1 group were anorexia (6.0%), nausea (3.7%), and diarrhea (3.1%).
CONCLUSIONS
S-1 is an effective adjuvant treatment for East Asian patients who have undergone a D2 dissection for locally advanced gastric cancer. (ClinicalTrials.gov number, NCT00152217 [ClinicalTrials.gov].).
Topics: Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Survival Rate; Tegafur
PubMed: 17978289
DOI: 10.1056/NEJMoa072252 -
Journal of Clinical Oncology : Official... May 2019S-1 is a standard postoperative adjuvant chemotherapy for patients with stage II or III gastric cancer in Asia. Neoadjuvant or perioperative strategies dominate in... (Randomized Controlled Trial)
Randomized Controlled Trial
Addition of Docetaxel to Oral Fluoropyrimidine Improves Efficacy in Patients With Stage III Gastric Cancer: Interim Analysis of JACCRO GC-07, a Randomized Controlled Trial.
PURPOSE
S-1 is a standard postoperative adjuvant chemotherapy for patients with stage II or III gastric cancer in Asia. Neoadjuvant or perioperative strategies dominate in Western countries, and docetaxel has recently shown significant survival benefits when combined with other standard regimens in advanced cancer and perioperative settings.
PATIENTS AND METHODS
This randomized phase III study was designed to prove the superiority of postoperative S-1 plus docetaxel over S-1 alone for R0 resection of pathologic stage III gastric cancer. The sample size of 1,100 patients was necessary to detect a 7% increase in 3-year relapse-free survival as the primary end point (hazard ratio, 0.78; 2-sided α = .05; β = .2).
RESULTS
The second interim analysis was conducted when the number of events reached 216 among 915 enrolled patients (median follow-up, 12.5 months). Analysis demonstrated the superiority of S-1 plus docetaxel (66%) to S-1 (50%) for 3-year relapse-free survival (hazard ratio, 0.632; 99.99% CI, 0.400 to 0.998; stratified log-rank test, < .001), and enrollment was terminated as recommended by the independent data and safety monitoring committee. Incidences of grade 3 or greater adverse events, particularly neutropenia and leukopenia, were higher in the S-1 plus docetaxel group, but all events were manageable.
CONCLUSION
Addition of docetaxel to S-1 is effective with few safety concerns in patients with stage III gastric cancer. The present findings may also be applicable in countries in which perioperative adjuvant chemotherapy or chemoradiation is not standard.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Female; Gastrectomy; Humans; Male; Medication Adherence; Middle Aged; Neoplasm Staging; Oxonic Acid; Postoperative Care; Stomach Neoplasms; Tegafur
PubMed: 30925125
DOI: 10.1200/JCO.18.01138 -
Oncology (Williston Park, N.Y.) Oct 2000Over the past decade, increasing data have emphasized both the importance of dihydropyrimidine dehydrogenase (DPD), the initial, rate-limiting enzyme in the catabolism... (Review)
Review
Over the past decade, increasing data have emphasized both the importance of dihydropyrimidine dehydrogenase (DPD), the initial, rate-limiting enzyme in the catabolism of fluorouracil (5-FU), and its role as a control step in 5-FU metabolism, regulating the availability of 5-FU for anabolism. It is now clear that DPD also accounts for much of the variability observed with therapeutic use of 5-FU, including variabilities in 5-FU levels over a 24-hour infusion, interindividual pharmacokinetics, bioavailability, toxicity, and drug response (resistance). This variability makes effective dosing of 5-FU and related drugs difficult. In order to lessen this variability, and potentially improve 5-FU pharmacology, the pharmaceutical industry has made an effort to develop DPD inhibitors to modulate 5-FU metabolism, which has resulted in the creation of a new subclass of orally administered fluoropyrimidines, known as DPD-inhibiting fluoropyrimidines (DIF). Four drugs--uracil and tegafur (UFT) or the combination of UFT and leucovorin, ethynyluracil (eniluracil), S-1, and BOF-A2--have recently undergone clinical evaluation in the United States. The biochemical basis for using these drugs is reviewed.
Topics: Administration, Oral; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Biological Availability; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Drug Resistance, Neoplasm; Fluorouracil; Humans; Leucovorin; Oxidoreductases; Oxonic Acid; Pyridines; Tegafur; Uracil
PubMed: 11098485
DOI: No ID Found -
Dermatology Online Journal Nov 2019Drug-induced subacute cutaneous lupus erythematosus (SCLE) is the most common subtype of drug-induced systemic lupus erythematosus and has been associated with more than... (Review)
Review
Drug-induced subacute cutaneous lupus erythematosus (SCLE) is the most common subtype of drug-induced systemic lupus erythematosus and has been associated with more than 100 drugs. It presents weeks to months after initiation of the culprit medication. The eruption is typically in a photodistribution and it is marked by positive serology to anti-Ro (SSA) antibody. Systemic 5-fluorouracil (5-FU) is a less-common culprit of drug-induced SCLE and its occurrence is likely dependent on exposure to ultraviolet light. Herein, we present a review of drug-induced lupus induced by the pyrimidine analog, 5-FU, and its prodrugs, capecitabine and uracil-tegafur. The search was carried out using the following terms: (PubMed: keywords included drug-induced lupus, 5-fluorouracil, subacute cutaneous lupus erythematosus, capecitabine, uracil-tegafur, discoid lupus, systemic lupus erythematosus).
Topics: Age Distribution; Aged; Antimetabolites, Antineoplastic; Capecitabine; Female; Fluorouracil; Humans; Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Systemic; Male; Middle Aged; Sex Distribution; Tegafur
PubMed: 32045142
DOI: No ID Found -
ESMO Open Apr 2021The ACTS-CC 02 trial demonstrated that S-1 plus oxaliplatin (SOX) was not superior to tegafur-uracil and leucovorin (UFT/LV) in terms of disease-free survival (DFS) as... (Randomized Controlled Trial)
Randomized Controlled Trial
S-1 and oxaliplatin versus tegafur-uracil and leucovorin as post-operative adjuvant chemotherapy in patients with high-risk stage III colon cancer: updated 5-year survival of the phase III ACTS-CC 02 trial.
BACKGROUND
The ACTS-CC 02 trial demonstrated that S-1 plus oxaliplatin (SOX) was not superior to tegafur-uracil and leucovorin (UFT/LV) in terms of disease-free survival (DFS) as adjuvant chemotherapy for high-risk stage III colon cancer (any T, N2, or positive nodes around the origin of the feeding arteries). We now report the final overall survival (OS) and subgroup analysis according to the pathological stage (TNM 7th edition) for treatment efficacy.
PATIENTS AND METHODS
Patients who underwent curative resection for pathologically confirmed high-risk stage III colon cancer were randomly assigned to receive either UFT/LV (300 mg/m of UFT and 75 mg/day of LV on days 1-28, every 35 days, five cycles) or SOX (100 mg/m of oxaliplatin on day 1 and 80 mg/m/day of S-1 on days 1-14, every 21 days, eight cycles). The primary endpoint was DFS and the patients' data were updated in February 2020.
RESULTS
A total of 478 patients in the UFT/LV group and 477 patients in the SOX group were included in the final analysis. With a median follow-up time of 74.3 months, the 5-year DFS rate was 55.2% in the UFT/LV group and 58.1% in the SOX group [stratified hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.76-1.11; P = 0.3973], and the 5-year OS rates were 78.3% and 79.1%, respectively (stratified HR 0.97; 95% CI 0.76-1.24; P = 0.8175). In the subgroup analysis, the 5-year OS rates in patients with T4N2b disease were 51.0% and 64.1% in the UFT/LV and SOX groups, respectively (HR 0.72; 95% CI 0.40-1.31).
CONCLUSION
Our final analysis reconfirmed that SOX as adjuvant chemotherapy is not superior to UFT/LV in terms of DFS in patients with high-risk stage III colon cancer. The 5-year OS rate was similar in the UFT/LV and SOX groups.
Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Humans; Leucovorin; Neoplasm Staging; Oxaliplatin; Tegafur; Uracil
PubMed: 33714860
DOI: 10.1016/j.esmoop.2021.100077 -
Nagoya Journal of Medical Science Aug 2019Eye problems are an adverse reaction sometimes found in chemotherapy. Although not life-threatening, they can reduce patients' quality of life. The highest incidence of...
Eye problems are an adverse reaction sometimes found in chemotherapy. Although not life-threatening, they can reduce patients' quality of life. The highest incidence of eye problems is reported for the combination anticancer drug S-1 (tegafur-gimeracil-oteracil), and methods to prevent or treat the eye problems caused by this drug are presently lacking. To determine early detection methods and treatment for adverse ocular reactions, we measured changes in tear volume and levels of tegafur (FT) and 5-fluorouracil (5-FU), an active metabolite of FT, in the tears of patients with long-term use of S-1. A total of 11 patients receiving S-1 monotherapy as adjuvant chemotherapy after gastric cancer surgery were included. Tear volume and FT and 5-FU levels in tears were measured by liquid chromatography with tandem mass spectrometry during a maximum of 8 treatment cycles (48 weeks). For analysis, patients were divided into two groups: "watering eyes" (n=6, complaints of watering eyes at least once during the treatment period) and "no watering eyes" (n=5, no complaints of watering eyes). Both groups exhibited increased FT and 5-FU levels in tears upon initiation of S-1 treatment, and levels rapidly decreased upon discontinuation. Our findings suggest a relationship between FT level in tears and tear volume in patients with long-term S-1 use. The symptom of watering eyes may thus be linked to FT level in tears.
Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Chromatography, Liquid; Drug Combinations; Female; Fluorouracil; Humans; Male; Middle Aged; Oxonic Acid; Quality of Life; Tandem Mass Spectrometry; Tears; Tegafur
PubMed: 31579332
DOI: 10.18999/nagjms.81.3.415 -
Health Technology Assessment... 2003To evaluate the clinical and cost-effectiveness of capecitabine and tegafur with uracil (UFT/LV) as first-line treatments for patients with metastatic colorectal cancer,... (Review)
Review
OBJECTIVES
To evaluate the clinical and cost-effectiveness of capecitabine and tegafur with uracil (UFT/LV) as first-line treatments for patients with metastatic colorectal cancer, as compared with 5-fluorouracil/folinic acid (5-FU/FA) regimens.
DATA SOURCES
Electronic databases, reference lists of relevant articles and sponsor submissions were also consulted.
REVIEW METHODS
Systematic searches, selection against criteria and quality assessment were performed to obtain data from relevant studies. Costs were estimated through resource-use data taken from the published trials and the unpublished sponsor submissions. Unit costs were taken from published sources, where available. An economic evaluation was undertaken to compare the cost-effectiveness of capecitabine and UFT/LV with three intravenous 5-FU/LV regimens widely used in the UK: the Mayo, the modified de Gramont regimen and the inpatient de Gramont regimens.
RESULTS
The evidence suggests that treatment with capecitabine improves overall response rates and has an improved adverse effect profile in comparison with 5-FU/LV treatment with the Mayo regimen, with the exception of hand-foot syndrome. Time to disease progression or death after treatment with UFT/LV in one study appears to be shorter than after treatment with 5-FU/LV with the Mayo regimen, although it also had an improved adverse effect profile. Neither capecitabine nor UFT/LV appeared to improve health-related quality of life. Little information on patient preference was available for UFT/LV, but there was indicated a strong preference for this over 5-FU/LV. The total cost of capecitabine and UFT/LV treatments were estimated at 2111 pounds and 3375 pounds, respectively, compared with the total treatment cost for the Mayo regimen of 3579 pounds. Cost estimates were also presented for the modified de Gramont and inpatient de Gramont regimens. These were 3684 pounds and 6155 pounds, respectively. No survival advantage was shown in the RCTs of the oral drugs against the Mayo regimen. Cost savings of capecitabine and UFT/LV over the Mayo regimen were estimated to be 1461 pounds and 209 pounds, respectively. Drug acquisition costs were higher for the oral therapies than for the Mayo regimen, but were offset by lower administration costs. Adverse event treatment costs were similar across the three regimens. It was inferred that there was no survival difference between the oral drugs and the de Gramont regimens. Cost savings of capecitabine and UFT/LV over the modified de Gramont regimen were estimated to be 1353 pounds and 101 pounds, respectively, and over the inpatient de Gramont regimen were estimated to be 4123 pounds and 2870 pounds, respectively.
CONCLUSIONS
The results show that there are cost savings associated with the use of oral therapies. No survival difference has been proven between the oral drugs and the Mayo regimen. In addition, no evidence of a survival difference between the Mayo regimen and the de Gramont regimens has been identified. However, improved progression-free survival and an improved adverse event profile have been shown for the de Gramont regimen over the Mayo regimen. Further research is recommended into the following areas: quality of life data should be included in trials of colorectal cancer treatments; the place of effective oral treatments in the treatment of colorectal cancer, the safety mechanisms needed to ensure compliance and the monitoring of adverse effects; the optimum duration of treatment; the measurement of patient preference; and a phase III comparative trial of capecitabine and UFT/LV versus modified de Gramont treatment to determine whether there was any survival advantage and to collate the necessary economic data.
Topics: Antimetabolites, Antineoplastic; Capecitabine; Colorectal Neoplasms; Cost-Benefit Analysis; Deoxycytidine; Drug Therapy, Combination; Fluorouracil; Humans; Neoplasm Metastasis; Tegafur; United Kingdom; Uracil
PubMed: 14604497
DOI: 10.3310/hta7320 -
BMJ Open Jun 2020Anlotinib hydrochloride is a multi-targeted receptor tyrosine kinase inhibitor that targets angiogenesis-related kinases and has already showed good safety and efficacy... (Clinical Trial)
Clinical Trial
Anlotinib combined with SOX regimen (S1 (tegafur, gimeracil and oteracil porassium capsules) + oxaliplatin) in treating stage IV gastric cancer: study protocol for a single-armed and single-centred clinical trial.
INTRODUCTION
Anlotinib hydrochloride is a multi-targeted receptor tyrosine kinase inhibitor that targets angiogenesis-related kinases and has already showed good safety and efficacy in some solid tumours. However, evidence on the safety and feasibility of anlotinib in patients with stage IV gastric cancer is scarce.
METHODS AND ANALYSIS
This study is a single-armed and single-centred clinical study being designed to include 150 patients of stage IV gastric cancer. The patients' demographics, pathological characteristics, test results of blood, biochemistry and tumour markers before and after medication, disease-free survival and overall survival will be collected and analysed. The primary and main efficacy outcomes are objective response rate, progression-free survival, disease control rate and overall survival. The secondary efficacy outcome is safety indicator including the incidence of adverse drug reactions and adverse events after administration.
ETHICS AND DISSEMINATION
Ethics approval has been obtained from the Ethics Committee at the First Affiliated Hospital (Xijing Hospital) of Fourth Military Medical University (KY20192111-F-1). The results of this study will be disseminated at several research conferences and as published articles in peer-reviewed journals.
TRIAL REGISTRATION NUMBER
ChiCTR1900026291 (registration date: 29 September 2019).
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Female; Humans; Male; Middle Aged; Neoplasm Staging; Oxaliplatin; Oxonic Acid; Progression-Free Survival; Pyridines; Stomach Neoplasms; Tegafur; Treatment Outcome
PubMed: 32499264
DOI: 10.1136/bmjopen-2019-034685