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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 -
The Oncologist May 2021The 3-year disease-free survival rate of the twice-daily regimen was not inferior to that of the conventional three-times-daily regimen, and the twice-daily regimen did... (Randomized Controlled Trial)
Randomized Controlled Trial
LESSONS LEARNED
The 3-year disease-free survival rate of the twice-daily regimen was not inferior to that of the conventional three-times-daily regimen, and the twice-daily regimen did not lead to an increase in adverse events. The effectiveness of the twice-daily regimen highlights an increased number of treatment options for patients. This will facilitate personalized medicine, particularly for elderly or frail patients who may experience more severe side effects from the combination therapy.
BACKGROUND
Tegafur-uracil (UFT)/leucovorin calcium (LV) is an adjuvant chemotherapy treatment for colorectal cancer. We conducted a multicenter randomized trial to assess the noninferiority of a twice-daily compared with a three-times-daily UFT/LV regimen for stage II/III colorectal cancer in an adjuvant setting.
METHODS
Patients were randomly assigned to group A (three doses of UFT [300 mg/m per day]/LV [75 mg per day]) or B (two doses of UFT [300 mg/m per day]/LV [50 mg per day]). The primary endpoint was 3-year disease-free survival.
RESULTS
In total, 386 patients were enrolled between July 28, 2011, and September 27, 2013. The 3-year disease-free survival rates of group A (n = 194) and B (n = 192) were 79.4% and 81.4% (95% confidence interval, 72.6-84.4-74.5-85.9), respectively. The most common grade 3/4 adverse events in group A and B were diarrhea (3.9% vs. 7.3%), neutropenia (2.9% vs. 1.6%), increase in aspartate aminotransferase (4.0% vs. 3.9%), increase in alanine aminotransferase (6.2% vs. 6.8%), nausea (1.7% vs. 3.4%), and fatigue (1.1% vs. 2.3%).
CONCLUSION
Group B outcomes were not inferior to group A outcomes, and adverse events did not increase.
Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Calcium; Chemotherapy, Adjuvant; Colorectal Neoplasms; Humans; Leucovorin; Tegafur; Uracil
PubMed: 33604941
DOI: 10.1002/onco.13724 -
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 -
World Journal of Gastroenterology Aug 2017Tegafur-uracil has been reported to have only minor adverse effects and is associated with liver injury in 1.79% of Japanese patients. The development of...
Tegafur-uracil has been reported to have only minor adverse effects and is associated with liver injury in 1.79% of Japanese patients. The development of tegafur-uracil-induced hepatic fibrosis with portal hypertension is rare. Here, we report a case of a 74-year-old woman with rapidly developing tegafur-uracil-induced hepatic fibrosis. The patient had no history of liver disease and had been treated with tegafur-uracil for 8 mo after breast cancer surgery. The patient was admitted to our hospital for abdominal distension and leg edema associated with liver dysfunction. Computed tomography imaging revealed massive ascites and splenomegaly, and a non-invasive assessment of liver fibrosis indicated advanced fibrosis. The histopathological findings revealed periportal fibrosis and bridging fibrosis with septation. The massive ascites resolved after discontinuing tegafur-uracil. These findings suggest that advanced hepatic fibrosis can develop from a relatively short-term administration of tegafur-uracil and that non-invasive assessment is useful for predicting hepatic fibrosis.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Biopsy; Carcinoma, Hepatocellular; Diuretics; Female; Humans; Hypertension, Portal; Liver; Liver Cirrhosis; Liver Neoplasms; Tegafur; Time Factors; Tomography, X-Ray Computed; Uracil; Withholding Treatment
PubMed: 28883709
DOI: 10.3748/wjg.v23.i31.5823 -
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 -
Annals of Oncology : Official Journal... Aug 2008Major achievements in the treatment of localised rectal cancer include the development of total mesorectal excision and the perioperative administration of radiotherapy... (Review)
Review
BACKGROUND
Major achievements in the treatment of localised rectal cancer include the development of total mesorectal excision and the perioperative administration of radiotherapy in combination with continuous infusion (CI) 5-fluorouracil (5-FU). This multimodal approach has resulted in extended survival and lower local relapse rates, with the potential for sphincter-preserving procedures. However, CI 5-FU is inconvenient for patients and is costly. Oral fluoropyrimidines like UFT (tegafur-uracil) offer a number of advantages over 5-FU.
METHODS
We undertook a review of published articles and abstracts relating to clinical studies of UFT in the treatment of locally advanced rectal cancer (LARC). Pre- and postoperative studies carried out in patients with newly diagnosed or recurrent disease were included.
RESULTS
The combination of UFT and radiotherapy was effective and well tolerated in the preoperative setting, while adjuvant UFT improved survival and reduced distant relapse compared with surgery alone. The efficacy of UFT appears comparable with that of 5-FU and capecitabine and its side-effect profile is favourable.
CONCLUSION
Clinical experience to date suggests that UFT is a valuable treatment option for the perioperative treatment of LARC. Further improvements in patient outcomes may result from the combination of UFT with targeted agents.
Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Humans; Rectal Neoplasms; Tegafur; Uracil
PubMed: 18381370
DOI: 10.1093/annonc/mdn067 -
Oncology (Williston Park, N.Y.) Oct 2000The mechanism of action of fluorouracil (5-FU) and the oral fluoropyrimidines and the importance of biochemical modulation and inhibition of dihydropyrimidine... (Review)
Review
The mechanism of action of fluorouracil (5-FU) and the oral fluoropyrimidines and the importance of biochemical modulation and inhibition of dihydropyrimidine dehydrogenase for oral application of the prodrugs of 5-FU are discussed. The regulation of thymidylate synthase, as well as its roles as a target for antineoplastic activity and in drug resistance, are also mentioned. The more downstream events of 5-FU action and their implication in 5-FU resistance, with the possible involvement of the Fas/FasL system and the proteins associated with apoptosis regulation, are highlighted. Also discussed is the suggestion that the oral 5-FU prodrug tegafur and uracil (UFT) and its metabolites function as an angiogenesis inhibitor.
Topics: Administration, Oral; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Drug Resistance, Neoplasm; Drug Therapy, Combination; Fluorouracil; Humans; Tegafur; Thymidylate Synthase; Uracil
PubMed: 11098484
DOI: No ID Found