gimeracil and potassium-oxonate

To observe the efficacy and safety of chemotherapy regimens oxaliplatin combined with capecitabine (CAPOX) or oxaliplatin combined with tegafur, gimeracil and oteracil potassium capsules (S-1)(SOX), and to investigate the value of expression of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) proteins in tumor tissue for predicting the efficacy of CAPOX and SOX regimens in advanced gastric cancer patients.. A total of 107 newly-diagnosed, stage Ⅲc/Ⅳ gastric cancer patients (no surgical indication, ECOG performance scores 0-2 and expected survival time ≥3 months) were recruited with 101 patients evaluated. The patients were randomly divided into two groups. One was study group in which the patients received CAPOX regimen. The other was control group received SOX regimen. Each patient received four cycles, at least two cycles chemotherapy every three weeks and followed up until death or lost. Tumor biopsies were obtained by gastroscopy for immunohistochemical examination of the expression of TP and DPD proteins before chemotherapy. Response rate (ORR), overall survival (OS) and time to tumor progression (TTP) of the patients were assessed.. The objective response rate (ORR) of the study and control groups was 49.0% (5/51) vs. 46.0% (23/50), respectively (P>0.05). The overall survival (OS) was 357.36±24.69 days in the study group and 349.87±22.63 days in the control group, and the time-to-progression (TTP) was 216.75±19.32 days in the study group and 220.54±18.47 days in the control group (P>0.05 for both). Stratified analysis showed that the ORR of TP-positive patients in the study group was significantly higher than that in the control group (72.0 % vs. 41.7 %, P=0.032). There was no significant difference in ORR between the TP-negative patients in the study and control groups (26.9% vs. 50.0%, P=0.087), while the ORR of DPD-positive patients in the control group was significantly higher than that of the study group (51.9% vs. 34.6%, P=0.046). There was no significant difference in the ORR between DPD-negative patients in the study and control groups (64.0% vs. 39.1%, P=0.084). The follow-up showed that the OS (378.42±22.56 days) and TTP (271.77±24.92 days) in the TP-positive patients of the study group were significantly longer than those of the control group (OS: 326.57±19.84 days, and TTP: 229.13±22.68 days)( P<0.05). The OS was 371.25±23.97 days and TTP was 264.66±21.36 days in the DPD-positive patients of control group, significantly longer than those of the study group (OS: 334.73±21.47days, and TTP: 208.58±20.70 days) (P<0.05). But there was no significant difference in the OS and TTP between the TP- and DPD-negative patients in the two groups (P>0.05). In respect of adverse events, both the rates of hematological and non-hematological toxicities were low and similar between the two groups (P>0.05), and well-tolerated by the patients.. Both CAPOX and SOX regimens are effective chemotherapeutic protocols in treatment of patients with advanced gastric cancer. The expression levels of TP and DPD in tumor tissue can be used as a predictive factor for the efficacy of capecitabine or tegafur, gimeracil and oteracil potassium capsules combined with oxaliplatin regimens. CAPOX chemotherapy regimen is more suitable for the TP-positive gastric cancer patients, and SOX regimen is more suitable for the DPS-positive gastric cancer patients.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Capsules; Dihydrouracil Dehydrogenase (NADP); Disease Progression; Humans; Neoplasm Proteins; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur; Thymidine Phosphorylase

We conducted a phase II study to evaluate the efficacy and safety of S-1 plus cisplatin with bevacizumab followed by maintenance bevacizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC).. Chemotherapy-naïve patients received S-1 plus cisplatin with bevacizumab. S-1 (80 mg/m(2)) was administered orally twice daily for 14 days, cisplatin (60 mg/m(2)) on day 1, and bevacizumab (15 mg/kg) on day 1 and every 3 weeks for 4-6 cycles. Patients with an objective response or stable disease received maintenance bevacizumab every 3 weeks until disease progression.. Thirty patients were enrolled in this study. The median number of chemotherapy was four (range, 1-6 cycles), and the median number of bevacizumab alone was three (range, 1-31 cycles). The grade 3/4 toxicities were neutropaenia (23%), thrombocytopaenia (10%), febrile neutropaenia (3%), hypertension (17%), pneumonia (7%), and bowel perforation (3%). The objective response rate was 71% (95% CI, 55-88%) for a disease control rate of 100%. The median progression-free and overall survival times were 7.0 months and 20.0 months, respectively.. S-1 plus cisplatin with bevacizumab is an active and well-tolerated regimen in patients with chemotherapy-naïve non-squamous NSCLC.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Cisplatin; Disease-Free Survival; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pyridines; Tegafur; Treatment Outcome

To observe the efficacy and side effects of the combination therapy of oxaliplatin and S-1 in treating postoperative colorectal cancer patients.. 54 postoperative colorectal cancer patients received the combination therapy of oxaliplatin and S-1 regimen, repeated every 3 weeks, and evaluate the efficacy after 3 cycles.. All of the 54 patients but 2 (changed the chemotherapy regimen after the first cycle because of economic reason) finished 6 cycles of the chemotherapy treatment. There were 6 cases (11.5%) with complete response (CR), 28 cases (53.8%) with partial response (PR), and the overall response rate was 65.4%. Major adverse effects were hematological toxicities, gastrointestinal disturbance, neurosensory toxicity. There were no chemotherapy-related deaths.. Oxaliplatin combined with S-1 is an effective and better tolerated chemotherapy treatment for postoperative colorectal cancer patients, with no serious side effects for liver and kidney. Therefore, it can be used as an alternative chemotherapy regimen for postoperative colorectal cancer patients.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Diarrhea; Female; Humans; Leukopenia; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Postoperative Period; Pyridines; Rectal Neoplasms; Remission Induction; Tegafur; Vomiting

To determine the clinical toxicities and antitumor effects of a chemotherapy regimen of FTQ, a compound preparation of tegafur, the drug prototype of 5-furacil (5-FU), gimeracil (CDHP), a decomposition inhibitor of 5-FU, oteracil potassium, phosphorylation inhibitor of 5-FU, and combined with cisplatin in patients with inoperable locally or metastatic advanced gastric cancer.. 119 patients with inoperable locally or metastatic advanced gastric cancer admitted in 10 hospitals in China were divided into 2 groups: FTQ group (n = 59), undergoing a 3-week regime, i.e. oral use of 80 mg x m(-2) x d(-1) for 14 d and then discontinuance for 1 week and intravenous drip cisplatin 75 mg/m2 on days 1-3; and control group (n = 60) undergoing a 3-week regimen including oral use of tegafur 800 mg x m(-2) x d(-1) tid for 14 d and then discontinuance for 1 week and intravenous drip of cisplatin 75 mg/m2 on days 1-3. The curative was evaluated after at least after 2 regimens.. There were 102 patients in the per-protocol population. The overall response rate of the FTQ group was 28. 3% (15/53), significantly higher than that of the control group (4.1%, 2/49, P = 0.004). The clinical improvement of the FTQ group was 50.9%, significantly higher than that of the control group (24.5%, P = 0.006). The main toxicities occurred in bone marrow and the digestive tract. The leucopenia and thrombocytopenia rates of the FTQ group were 47.45% and 32.22% respectively, both similar to those of the control group. There were no differences in the incidence rate of digestive canal side reaction between these 2 groups .. The regimen of FTQ combined with cisplatin is generally well-tolerated and has substantial antitumor activity.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Female; Fluorouracil; Humans; Middle Aged; Oxonic Acid; Pyridines; Single-Blind Method; Stomach Neoplasms; Tegafur; Treatment Outcome

The study is to investigate the pharmacokinetics of S-1 capsule (tegafur, gimeracil and potassium oxonate capsule) in patients with advanced gastric cancer after single and multiple oral administration. Twelve patients with advanced gastric cancer were recruited to the study. The dose of S-1 for each patient was determined according to his/her body surface area (BSA). The dose for single administration was 60 mg every subject. The dose for multiple administration for one subject was as follows: 100 mg x d(-1) or 120 mg x d(-1), 28-days consecutive oral administration. The pharmacokinetic parameters of tegafur, 5-fluorouracil, gimeracil, potassium oxonate and uracil after single oral administration were as follows: (2,207 +/- 545), (220.0 +/- 68.2), (374.9 +/- 103.0), (110.5 +/- 100.8) and (831.1 +/- 199.9) ng x mL(-1) for Cmax; (11.8 +/- 3.8), (4.4 +/- 3.3), (7.8 +/- 5.1), (3.1 +/- 0.9) and (8.8 +/- 4.1) h for t1/2, respectively. After six days oral administration, the average steady state plasma concentrations (Cav) of tegafur, 5-fluorouracil, gimeracil, potassium oxonate and uracil were (2,425 +/- 1,172), (73.88 +/- 18.88), (162.6 +/- 70.8), (36.89 +/- 29.35) and (435.3 +/- 141.0) ng x mL(-1), respectively, and the degree of fluctuation (DF) were (1.0 +/- 0.2), (2.5 +/- 0.4), (3.1 +/- 0.8), (2.4 +/- 0.8) and (1.5 +/- 0.3), respectively. The cumulative urine excretion percentage of tegafur, 5-fluorouracil, gimeracil and potassium oxonate in urine within 48 h were (4.2 +/- 2.8) %, (4.7 +/- 1.6) %, (18.5 +/- 6.0) % and (1.7 +/- 1.2) %, repectively, after single oral administration of S-1. The results exhibited that tegafur had some drug accumulation observed, and gimeracil, potassium oxonate, 5-fluorouracil and uracil had no drug accumulation observed.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Capsules; Drug Combinations; Female; Fluorouracil; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur; Uracil

To assess the efficacy and toxicity of radical chemoradiotherapy for patients with synchronous head and neck squamous cell carcinoma (HNSCC) and esophageal cancer (EC).. Thirty-four patients with synchronous HNSCC and EC were treated mainly with radical chemoradiotherapy at the same time. Median external radiation dose for HNSCC and EC was 70 Gy (range, 60-70.5 Gy), except for 2 patients with tongue cancer, who underwent brachytherapy and 60 Gy (range, 45-70 Gy), respectively. Thirty-one patients were treated with concurrent chemoradiotherapy with cisplatin and/or 5-fluorouracil or TS-1 (oral anticancer agent that combines tegafur, a metabolically activated prodrug of 5-fluorouracil, with 5-chloro-2, 4-dihydoroxypyridine, and potassium oxonate).. Thirty-three patients completed the intended treatment. The response rate was 94%, with 26 complete responses (76%) and 6 partial responses (18%). At a median follow-up of 17.3 months, 2-year rates of overall survival, cause-specific survival, and disease-free survival were 44%, 52%, and 33%, respectively. Initial failure patterns were local failure in 14 patients (63%), regional progression in 3 patients (13%), and distant metastasis in 6 patients (27%). The most common acute toxicity was myelosuppression, with 8 patients experiencing grade 3-4 toxicity. Three patients experienced grade 3 mucositis and pharyngitis. No patients experienced late morbidity of grade 3 or higher.. Definitive chemoradiotherapy for patients with synchronous HNSCC and EC is feasible with a low mortality rate and acceptable morbidity.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Carcinoma, Squamous Cell; Cisplatin; Cohort Studies; Combined Modality Therapy; Esophageal Neoplasms; Female; Fluorouracil; Follow-Up Studies; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Neoplasms, Multiple Primary; Oxonic Acid; Pyridines; Remission Induction; Retrospective Studies; Survival Rate; Tegafur; Treatment Outcome

Malignant pleural mesothelioma (MPM) is a highly lethal neoplasm. S-1 has been developed as a novel oral antineoplastic agent based on the modulation of 5-fluorouracil (5-FU) bioactivity. This study was conducted to investigate the preclinical therapeutic effect of S-1 on MPM.. We used three human MPM cell lines, Y-MESO-14, NCI-H290 and MSTO-211H. In vitro proliferation of human MPM cells was determined by MTT assay. Human MPM cells were orthotopically implanted into thoracic cavity of SCID mice. Tumor-bearing mice were treated with S-1 or vehicle.. The combination of 5-FU and 5-chloro-2,4-dihydroxypyridine (CDHP) was more effective than 5-FU alone in inhibiting MPM cell proliferation in vitro. This combination was most effective in Y-MESO-14 cells, which co-expressed high protein level of dihydropyrimidine dehydrogenase (DPD) and thymidine phosphorylase (TP). In vivo data showed that treatment with S-1 significantly reduced thoracic tumors and pleural effusion produced by Y-MESO-14 cells. Moreover, treatment with S-1 prolonged the survival of Y-MESO-14 cell-bearing SCID mice.. We demonstrated that S-1 was effective for inhibiting the proliferation of MPM cells, particularly with both DPD and TP expressions, suggesting that S-1 might be therapeutically effective for control of MPM.

Topics: Animals; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Enzyme Inhibitors; Humans; Male; Mesothelioma; Mice; Mice, SCID; Neoplasm Proteins; Oxonic Acid; Pentosyltransferases; Pleural Neoplasms; Pyridines; Random Allocation; Survival Analysis; Tegafur; Thymidine Phosphorylase; Tumor Burden; Xenograft Model Antitumor Assays

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Administration, Oral; Anti-Ulcer Agents; Antimetabolites, Antineoplastic; Area Under Curve; beta-Alanine; Biological Availability; Clinical Trials as Topic; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Fasting; Fluorouracil; Food; Gastric Acidity Determination; Half-Life; Humans; Hydrogen-Ion Concentration; Oxonic Acid; Pantoprazole; Pyridines; Tegafur; Triazines; Uracil

The purposes of this study were to evaluate the antitumor activity of S-1 (1 M tegafur, 0.4 M 5-chloro-2,4-dihydroxypyridine and 1 M potassium oxonate) on human lung tumor xenografts, as compared with other fluoro-pyrimidines, and to investigate the relationships between fluoropyrimidine antitumor activities and four distinct enzymatic activities involved in the phosphorylation and degradation pathways of 5-fluorouracil (5-FU) metabolism. S-1, UFT (1 M tegafur-4 M uracil), 5'-deoxy-5-fluorouridine (5'-DFUR), capecitabine and 5-FU were administered for 14 consecutive days to nude mice bearing lung tumor xenografts. S-1 showed stronger tumor growth inhibition in four of the seven tumors than the other drugs. Cluster analysis, on the basis of antitumor activity, indicated that S-1/UFT and 5'-DFUR/capecitabine/5-FU could be classified into another group. We investigated tumor thymidylate synthase content, dihydropyrimidine dehydrogenase (DPD) activity, thymidine phosphorylase (TP) activity and orotate phosphoribosyl transferase activity in seven human lung tumor xenografts and performed regression analyses for the antitumor activities of fluoropyrimidines. There were inverse correlations between antitumor and DPD activities for 5'-DFUR (r=-0.79, P=0.034), capecitabine (r=-0.56, P=0.19) and 5-FU (r=-0.86, P=0.013). However, no such correlations were observed for S-1 and UFT. These findings suggest that S-1 containing a potent DPD inhibitor may have an antitumor effect on lung tumors, with high basal DPD activity, superior to those of other fluoropyrimidines.

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Cell Line, Tumor; Deoxycytidine; Dihydrouracil Dehydrogenase (NADP); Floxuridine; Fluorouracil; Humans; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Orotate Phosphoribosyltransferase; Oxonic Acid; Pyridines; Tegafur; Thymidine Phosphorylase; Treatment Outcome; Uracil; Xenograft Model Antitumor Assays