• TS-1
• dog
• intranasal tumor
• toceranib phosphate

• Animals
• Dogs
• Dog Diseases/drug therapy
• Tegafur/administration & dosage
• Tegafur/therapeutic use
• Pyridines/administration & dosage
• Pyridines/therapeutic use
• Male
• Female
• Drug Combinations
• Indoles/administration & dosage
• Indoles/therapeutic use
• Pyrroles/administration & dosage
• Pyrroles/therapeutic use
• Oxonic Acid/administration & dosage
• Oxonic Acid/therapeutic use
• Nose Neoplasms/veterinary
• Nose Neoplasms/drug therapy
• Antineoplastic Combined Chemotherapy Protocols/administration & dosage
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Drug Administration Schedule

• Clinical trial results
• SOXIRI
• Unresectable pancreatic ductal adenocarcinoma

• Humans
• Irinotecan
• Oxaliplatin
• Pancreatic Neoplasms/drug therapy
• Neutropenia
• Adenocarcinoma/drug therapy
• Pain

• Adjuvant chemotherapy
• Carcinoma
• Multicenter study
• Pancreas
• Prospective study

• Humans
• Chemotherapy, Adjuvant/adverse effects
• Disease-Free Survival
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/surgery

Tegafur is a prodrug of fluoropyrimidine 5-fluorouracil (5-FU), while TS-1^TM is an oral fixed-dose combination of three active drugs, tegafur, gimeracil, and oteracil. This pilot study evaluated the safety of tegafur/gimeracil/oteracil in the treatment of cancers in dogs. Tegafur/gimeracil/oteracil was administered orally at a mean dose of 1.1 mg/kg twice daily on alternate days, Monday-Wednesday-Friday, every week to 11 dogs with tumors. Partial response and stable disease were observed in one dog each, whereas six exhibited progressive disease. Three dogs were not assessed. Adverse events, the most serious being grade 2, were noted in seven dogs. Adverse events were acceptable, and the drug was effective in some dogs. Therefore, tegafur/gimeracil/oteracil may be useful for treating malignant solid tumors in canines.

• 5-fluorouracil
• TS-1
• Teysuno
• dog
• tumor

• Adjuvant chemotherapy
• Alternate-day administration
• Non-small cell lung cancer
• S-1

• Adult
• Aged
• Carcinoma, Non-Small-Cell Lung/drug therapy
• Carcinoma, Non-Small-Cell Lung/mortality
• Carcinoma, Non-Small-Cell Lung/pathology
• Chemotherapy, Adjuvant
• Drug Administration Schedule
• Drug Combinations
• Female
• Humans
• Lung Neoplasms/drug therapy
• Lung Neoplasms/mortality
• Lung Neoplasms/pathology
• Male
• Middle Aged
• Neoplasm Staging
• Oxonic Acid/administration & dosage
• Oxonic Acid/adverse effects
• Tegafur/administration & dosage
• Tegafur/adverse effects

• Taiho Pharmaceutical

• S-1
• bevacizumab
• lung cancer
• non-squamous NSCLC
• progression free survival

• Bevacizumab
• Colorectal cancer
• Elderly
• Fluoropyrimidine
• S-1

Although triplet regimen of docetaxel, cisplatin, and 5-FU (DCF) reportedly yields high response rates for metastatic squamous cell carcinoma of the esophagus (SCCE), it has severe toxicity. In our previous phase II trial, grade 3/4 toxicities of neutropenia occurred in 68.8% of the patients. Development of chemotherapeutic regimen that does not impair quality of life of the patients with metastatic SCCE is therefore needed. A novel chemotherapeutic regimen combining docetaxel, cisplatin, and alternate-day administration of S-1 (modified DCS) may be associated with reduction of severe adverse effects.

This study is a single center phase I/II trial of chemotherapy using modified DCS regimen for patients with recurrent/unresectable SCCE. The phase I trial adopts a ‘3 + 3 patient cohort’, dose-escalating study design. In the phase II trial, the primary endpoint is evaluation of the overall response rate (ORR). Secondary endpoints are evaluation of drug-related toxicity, overall survival (OS), and progression-free survival (PFS).

In the phase I trial, the recommended dose for docetaxel, cisplatin, and S-1 were 40 mg/m² (day 1), 50 mg/m² (day 1), and 80 mg/m²/day, respectively. In the phase II trial (n = 50), the ORR was 54 %. The median OS and PFS were 10 and 4 months, respectively. Grade 3/4 adverse events included neutropenia (26%), leukopenia (14%), anorexia (10%) and febrile neutropenia (6%).

The modified DCS therapy for patients with advanced SCCE is feasible and safe in both chemotherapeutic and perioperative periods.

Registration number: UMIN000016364.

• S-1
• cisplatin
• docetaxel
• esophageal cancer
• squamous cell carcinoma

• Adenocarcinoma/drug therapy
• Adenocarcinoma/pathology
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Carcinoma, Pancreatic Ductal/drug therapy
• Carcinoma, Pancreatic Ductal/pathology
• Cohort Studies
• Drug Combinations
• Female
• Follow-Up Studies
• Humans
• Irinotecan/administration & dosage
• Male
• Middle Aged
• Oxaliplatin/administration & dosage
• Oxonic Acid/administration & dosage
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/pathology
• Prognosis
• Tegafur/administration & dosage

• Alternate-day administration
• Metastatic colorectal carcinoma
• S-1
• Second-line

Although S-1 based chemotherapy for patients with advanced gastric cancer has generally been accepted in Japan, discontinuations of treatment have been reported due to grade 3 or more adverse events. The present randomized phase II study was conducted to test whether alternate-day administration of S-1 would be comparably efficient and reduce adverse events compared with conventional daily administration in the first-line chemotherapy for advanced gastric cancer.

132 patients with advanced gastric cancer were randomly assigned to 1:2 ratios to receive treatment with daily at a standard dose of 80 mg/m²/day or alternate-day administration group received S-1 on 4 days a week. The primary end point was progression-free survival (PFS), and the secondary end points were safety, overall survival, time to treatment failure (TTF), disease control rate, and response rate.

The 6-month PFS rate of the alternate-day administration group was 20.9% and failed to show significant difference from the pre-specified threshold at 15% (p = 0.117), whereas that of the daily administration group was 39.1% and significantly higher than the threshold (p = 0.001). The hazard ratio of the alternate-day administration group compared with the daily administration group was 1.753 (95% confidence interval (CI) 1.15–2.68, p = 0.010). With regard to OS, the hazard ratio of the alternate-day administration group compared with the daily administration group was 1.487 (95% CI 0.97–2.29, p = 0.072). The median TTF were 4.2 and 2.8 months in the daily and alternate-day administration group, respectively (p = 0.007).

The alternate-day administration of S-1 was not recommended as the first-line therapy for patients with advanced gastric cancer.

• Chemotherapy
• Gastric cancer
• Randomized phase II study
• S-1

The feasibility of the S-1 administration schedules (the 4-week versus the 2-week) showed no significant difference for adjuvant chemotherapy among pathological-Stage IA non–small-cell lung cancer patients.

The aim of this multicenter study was to determine the appropriate administration schedule for S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in patients with completely resected pathological-Stage IA (tumor diameter, 2–3 cm) non–small-cell lung cancer.

Patients were randomly assigned to receive adjuvant chemotherapy consisting of either the 4-week oral administration of S-1 (80–120 mg/body/day) followed by a 2-week rest (Group A), or the 2-week oral administration of S-1 (80–120 mg/body/day) followed by a 1-week rest (Group B). The duration of adjuvant chemotherapy was 1 year in both arms. The primary endpoint was compliance, namely drug discontinuation-free survival, which was calculated using the Kaplan–Meier method with log-rank test.

Eighty patients were enrolled in this study, and 76 patients actually received S-1 treatment. The drug discontinuation-free survival rates at 1 year were 49.1% in Group A and 52.7% in Group B (P = 0.373). The means of the relative dose intensities were 55.3% in Group A and 64.6% in Group B (P = 0.237). There were no treatment-related deaths. Patients with grade 3/4 toxicities were significantly more frequent in Group A (40.5%) than in Group B (15.4%, P = 0.021). The 2-year relapse-free survival rates were 97.5% in Group A and 92.5% in Group B, and the 2-year overall survival rates were 100% in both groups.

The feasibility showed no significant difference between the two groups among patients with completely resected Stage IA (tumor diameter, 2–3 cm) non–small-cell lung cancer.

• S-1
• adjuvant chemotherapy
• clinical trials
• non–small-cell lung cancer

• 5-FU
• Alternate-day administration
• Gastrointestinal toxicity
• Regulatory T cell
• S-1

• S-1
• adjuvant chemotherapy
• feasibility
• gastric cancer
• randomized controlled trial

AIM: To assess the efficacy and tolerability of S-1-based vs non-S-1-based chemotherapy in advanced gastric cancer (AGC).

METHODS: We extracted reported endpoints, including overall survival (OS), progression-free survival (PFS), time-to-treatment failure (TTF), objective response rate (ORR) and adverse effects, from randomized controlled trials identified in PubMed, the Cochrane library, Science Direct, EMBASE and American Society of Clinical Oncology meetings. Stata software was used to calculate the pooled values.

RESULTS: Seven randomized controlled trials involving 2176 patients were included in this meta-analysis. Compared to non-S-1-based regimens, the use of S-1-based regimens were associated with an increase in ORR (RR = 1.300; 95%CI: 1.028-1.645); OS (HR = 0.89; 95%CI: 0.81-0.99; P = 0.025), TTF (HR = 0.83; 95%CI: 0.75-0.92; P = 0.000), and a lower risk of febrile neutropenia (RR = 0.225; P = 0.000) and stomatitis (RR = 0.230; P = 0.032). OS, PFS and TTF were prolonged, especially in the Asian population. In subgroup analysis, statistically significant increases in ORR (RR = 1.454; P = 0.029), OS (HR = 0.895; P = 0.041) and TTF (HR = 0.832; P = 0.000) were found when S-1-based chemotherapy was compared to 5-fluorouracil (5-FU)-based chemotherapy. The incidence of leukopenia (RR = 0.584; P = 0.002) and stomatitis (RR = 0.230; P = 0.032) was higher in the 5-FU-based arm. S-1-based regimens had no advantage in ORR, OS, PFS, TTF and grade 3 or 4 adverse events over capecitabine-based regimens.

CONCLUSION: S-1-based chemotherapy may be a good choice for AGC because of longer survival times, better tolerance and more convenient use.

• S-1
• Advanced gastric cancer
• Chemotherapy
• First line treatment
• Meta-analysis

• Antimetabolites, Antineoplastic/administration & dosage
• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Chi-Square Distribution
• Disease Progression
• Disease-Free Survival
• Drug Combinations
• Humans
• Oxonic Acid/administration & dosage
• Risk Factors
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/mortality
• Stomach Neoplasms/pathology
• Survival Analysis
• Tegafur/administration & dosage
• Time Factors
• Treatment Outcome

• S-1
• adjuvant chemotherapy
• feasibility study
• non-small cell lung cancer

Dushinsky et al. left a great gift to human beings with the discovery of 5-fluorouracil (5-FU). Approximately 50 years have elapsed from that discovery to the development of S-1 (TS-1^®). The concept of developing an anticancer agent that simultaneously possesses both efficacy-enhancing and adverse reaction-reducing effects could be achieved only with a three-component combination drug. S-1 is an oral anticancer agent containing two biochemical modulators for 5-FU and tegafur (FT), a metabolically activated prodrug of 5-FU. The first modulator, 5-chloro-2,4-dihydroxypyridine (CDHP), enhances the pharmacological actions of 5-FU by potently inhibiting its degradation. The second modulator, potassium oxonate (Oxo), localizing in mucosal cells of the gastrointestinal (GI) tract after oral administration, reduces the incidence of GI toxicities by suppressing the activation of 5-FU in the GI tract. Thus, S-1 combines FT, CDHP and Oxo at a molar ratio of 1:0.4:1. In 1999–2007, S-1 was approved for the treatment of the following seven cancers: gastric, head and neck, colorectal, non-small cell lung, breast, pancreatic and biliary tract cancers. ‘S-1 and low-dose cisplatin therapy’ without provoking Grade 3 non-hematologic toxicities was proposed to enhance its clinical usefulness. Furthermore, ‘alternate-day S-1 regimen’ may improve the dosing schedule for 5-FU by utilizing its strongly time-dependent mode of action; the former is characterized by the low incidences of myelotoxicity and non-hematologic toxicities (e.g. ≤Grade 1 anorexia, fatigue, stomatitis, nausea, vomiting and taste alteration). These two approaches are considered to allow long-lasting therapy with S-1.