oxonic acid

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..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...

..The present study aimed to retrospectively evaluate the efficacy and safety of irinotecan plus cisplatin (IP) therapy after the failure of S-1 in patients with AGC...

..S-1 is an oral fluoropyrimidine that promises better and accessible treatment. This article identifies the risk factors for severe adverse events of S-1 from nationwide survey data...

..To investigate the efficacy and safety of the combination therapy of irinotecan (CPT-11) plus S-1 in patients with advanced gastric cancer at the dose recommended by a previous phase I study...

..8 and 26.3%, respectively, but all were manageable. The RR was 74% (14/19, 95% confidence interval: 54.9-90.6%), and the median survival day was 383. This regimen is considered to be active against AGC with acceptable toxicity...

..A phase II study of weekly paclitaxel combined with S-1, a novel oral fluoropyrimidine, was performed to evaluate the efficacy and tolerability in unresectable or metastatic gastric cancer...

..b>Oxonic acid was found to inhibit the phosphorylation of 5-FU to 5-fluorouridine-5'-monophosphate catalyzed by pyrimidine ..

..1 months. The one-year survival rates of the stage IIIB and IV patients were 30.7% and 47.4%, respectively. S-1 was considered to be an active single agent against NSCLC. Further study of S-1 with other active agents is warranted...

..The superior cytotoxicity of S-1 appears to be attributable to both an increased inhibition of DNA synthesis and an enhanced blockade of RNA function against tumours with a high DPD activity...

..We performed a phase 1/2 study to determine the recommended dose, antitumor activity, and safety of a combination of S-1 and irinotecan in patients with advanced gastric cancer...

..We investigated its clinical efficacy against metastatic breast cancer...

..The efficacy and adverse effects of CDDP plus S-1 should be studied in carefully designed phase II/III trials. S-1 will be one of the key drugs for HNSCC in the future...

..Down-regulation of the DPD activity of the tumors is also considered to be correlated with the antitumor effect of the treated groups, suggesting its influence on the synergistic effect of the combination therapy...

..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...

..The dose limiting toxicity of a combination of S-1 and biweekly DOC was leukopenia and neutropenia. The recommended dose for this combination in phase II study is DOC 35 mg/m2/day...

..Combined therapy with TS-1 and TXT showed enhanced antitumor activity compared with monotherapy of each drug. The outpatient-based treatment of this combination is worth investigating...

..The aim of this study was to evaluate the efficacy and toxicity of S-1 in patients with metastatic pancreatic cancer...

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..We have retrospectively examined the efficacy and safety of S-1 in patients with MBC who had been previously treated with anthracycline, taxane, and capecitabine...

..These results suggest that S-1 will have a higher clinical therapeutic effect against advanced squamous cell carcinoma of the head and neck in humans...

..Therefore, S-1 may be a new therapeutic agent to prolong the survival period of breast cancer patients due to its high antitumor activity and low toxicity...

..To determine the dose-limiting toxicity (DLT) and activity of combination with docetaxel and S-1 on unresectable gastric cancer...

..The authors review the current literature and provide their expert opinion on the incorporation of S-1 in the treatment of solid malignancies [corrected]...

..4 : 1. S-1 has a high response rate, of about 40%, in advanced gastric cancer. A phase I study was conducted to assess the maximum tolerated dose and the recommended dose of the combination of irinotecan and S-1...

..The aim of this phase I study was to determine the maximum-tolerated dose (MTD) and the recommended dose of docetaxel with a fixed dose of S-1 in patients with advanced or recurrent gastric cancer...

..As toxicities were well tolerated and antitumour activities seem to be promising, this combination can be recommended for further phase II studies with APC...

..These results have proven the utility of this post-marketing survey in assessing the reproducibility of the safety and efficacy results obtained from prior clinical studies...

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..v. and bolus 5-FU and the other oral fluoropyrimidines. Thus, we may finally be seeing the realization of oral treatments for the management of various solid tumors and could be on the brink of a new approach to treatment strategies...

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..CDHP)], and an inhibitor of orotate phosphoribosyltransferase [potassium oxonate (oxonic acid)], was developed to increase the feasibility and therapeutic index of 5-FU administered orally...

..S-1 exhibits definite antitumour activity and is well tolerated in patients with advanced biliary tract cancer...

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..In the present study, the efficacy and safety of a combination of S-1 and low-dose twice-weekly cisplatin were investigated...

..To determine the maximum tolerated dose (MTD), recommended dose (RD), and activity of combined docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy on metastatic gastric cancer...

..The purpose of this study was to evaluate the relationship between different schedules and the effects of GEM/S-1 combination therapy on pancreatic cancer xenograft models...

..5%), anorexia (7.5%) and T-Bil elevation (7.5%). Significant antitumor activity combined with a mild toxicity profile was observed. This monotherapy warrants further evaluation in a randomized study...

..This study examined the effect of five systemic chemotherapy regimens on survival in patients with unresectable biliary tract cancer (BTC) as compared with the best supportive care (BSC)...

..Briefly, this 2-week regimen may be a useful concurrent chemo-radiotherapy improving the quality of life (QOL) of patients with OSCC...

..Endpoints of this study were to examine the toxicity profile of this regimen and to determine the recommended dose of S-1...

..Optimal chemotherapy for advanced biliary tract cancer (BTC) is yet to be defined. We carried out this study to evaluate the efficacy and toxicity of combination chemotherapy with S-1 and cisplatin in metastatic or relapsed BTC...

..However, the dose of S-1 for patients who have undergone total gastrectomy might be diminished to avoid severe adverse events and to continue the treatment for a long period...

..We suggest that the pharmacogenomic markers identified in this study may be potential candidates for predicting anemia after S-1 treatment...

S-1 is a novel oral fluoropyrimidine that combines tegafur with CDHP and oxonic acid. To decrease the incidence of late onset, severe diarrhea observed in a previous study, a phase I study was conducted to determine the maximum tolerated ..

..012). CONCLUSION: Induction chemotherapy using S-1/CDDP for AGC appears to be a safe and promising treatment. We have therefore started two independent multiinstitutional clinical trials to evaluate the efficacy of this treatment...

..Median survival and 1-year survival rate were 12.5 months (95% CI, 5.9-19.1) and 54% (95% CI, 36-72), respectively. Combination chemotherapy with GEM and S-1 was well tolerated and yielded a significantly high response rate...

..These data strongly indicate that a combination chemotherapy of TXT and S-1 is effective against gastric carcinomas and is therefore a good candidate as a standard chemotherapeutic strategy in treating these tumors...

..We conducted a phase II multi-institutional trial, in the West, in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma to evaluate activity and safety of this combination...

..We aimed to investigate the superiority of irinotecan plus cisplatin and non-inferiority of S-1 compared with fluorouracil, with respect to overall survival, in patients with metastatic gastric cancer...

..The safety and efficacy of docetaxel plus S-1 combination chemotherapy as a first-line treatment in patients with advanced or recurrent gastric cancer was verified retrospectively...

..To assess the efficacy and safety of S-1, a novel oral fluoropyrimidine derivative, we conducted a multicenter late phase II study in patients with advanced gastric cancer...

..CONCLUSION: S-1 appears to be safe and highly active, with favorable longterm survival in patients with metastatic gastric cancer, particularly in those with diffuse-type histology and peritoneal metastasis...

..The pharmacokinetics for 5-FU and oteracil were similar between Western and Japanese patients, but apparent differences in exposure to 5-FU resulted from different total doses due to different body sizes...

..CONCLUSIONS: The recommended S-1 dose for future studies is 30 mg/m(2) twice daily, and diarrhea is the most frequent toxic effect. Additional trials of S-1 in the treatment of patients with solid tumors are warranted...

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..The AUC(0-10 h) of FBAL was markedly lower and plasma uracil concentrations were significantly higher for S-1 than for PVI of 5-FU, clearly demonstrating the effect of DPD inhibition...

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..Therefore, this event was confirmed to be reversible. Based on these results, we conclude that S-1 is an active agent for the treatment of advanced/recurrent head and neck cancer...

..Although NAC consisting of TS-1 and CDDP is considered to be effective against advanced gastric cancer, a phase III study with surgical treatment only will be necessary to confirm its true value...

..Microscopically, the histological effect was judged to be grade 1a. One year after the operation, the patient is still alive without recurrence and metastasis. TS-1/CDDP therapy is useful for advanced gastric cancer...

..The patient has now been in good health without a recurrence for 1 year and 9 months after surgery...

..The response rate to the drug was 23% in the 2-week-regimen group and 21% in the 4-week-regimen group. CONCLUSION: These results suggest that this 2-week regimen may mitigate adverse reactions and prolong the medication period...

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..The marked clinical response in this patient suggests that this combination therapy with CDDP and TS-1 might be a promising preoperative chemothepapy for unresectable gastric cancer...

..S-1 (TS-1), a combination of ftorafur and two modulators, gimestat (CDHP) and oxonic acid, in a molar ratio of 1:0...

..3. This case suggests that neoadjuvant chemotherapy using TS-1 plus CDDP is effective for advanced gastric adenosquamous carcinoma with massive lymph node metastases...

..The patient no longer experienced constipation or melena. Her clinical course is being observed while an oral administration of 100 mg/day of TS-1 continues...

..This chemotherapy was ended after the eighth course. The residual tumor did not disappear but did not grow, and a no change status was maintained for twelve months after the gastrectomy...

..Therefore, weekly paclitaxel therapy was considered to be one of the promising second-line chemotherapies for advanced or recurrent gastric cancer previously treated by TS-1...

..Because of the mild toxicity, most patients were treated at the outpatient clinic. CONCLUSIONS: Combination chemotherapy of S-1 and low-dose CDDP is expected to be a useful chemotherapy for advanced gastric cancer...

..These results suggested that combined chemotherapy with TS-1 and HAI with low-dose CDDP was not only useful for liver and lymph node metastases from gastric cancer, but for hepatocellular carcinoma as well...

..The patient sustained few side effects. This preoperative chemotherapy regimen seems to be an effective and promising therapy for patients with advanced gastric cancer...

..The only adverse effect was grade 2 pancytopenia. In conclusion this regimen resulted in good intrachemotherapeutic QOL and highly effective performance in elderly advanced gastric cancer patient...

..The dilatation of the intrahepatic bile ducts disappeared, and the liver function normalized. No side effects were evident during the treatment with the medications...

..g., appetite) was achieved. Based on these findings, this chemotherapy regimen appears to be an effective treatment modality for far advanced gastric cancer, particularly involving the abdominal para-aortic lymph nodes...

..Subsequently oral administration of TS-1 (80-100 mg/body/day) for 4 weeks was performed. All 3 patients are well without any signs of increase in tumor size...

..TS-1 as initial chemotherapy had to be abandoned for this patient because of a serious hepatic disorder, in which TS-1 administration is contraindicated. However, a favorable response was obtained by concomitant use of FP therapy...

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..Histrogical result showed PR. The patient is now healthy and no sign of recurrence has been observed. TS-1/CDDP therapy is useful for advanced gastric cancer...

..TS-1 may therefore be a new candidate as a first line drug in outpatient cancer treatment...

..No noteworthy adverse reactions were observed and the patient has a good QOL. The patient is now in a good health and continues to undergo low dose TS-1 plus CDDP chemotherapy as an outpatient...

..We speculate that this tumor could have developed the potency of SCC secretions without structural change into squamous metaplasia...

..The adverse effects observed with this drug were leucocytopenia and liver dysfunction, both of which improved soon. These results indicate paclitaxel is effective for advanced gastric cancer pretreated with TS-1...

..The high DPD activity of the tumor may have been one reason this treatment was effective. This case also seems significant from the viewpoint of attaining individualization of the drug selection in chemotherapy...

..The final diagnosis was Stage IIIA and the pathological response to chemotherapy was Grade 2. The patient has survived for over 14 months after surgery and has presented no signs of recurrence...

..The postoperative course was uneventful, and she has been fine as an outpatient...

..The patient has been alive for 1 year and a half after 14 courses of TS-1/CDDP with stable disease. Significance of TS-1/CDDP in far advanced gastric cancer was discussed...

..Immuno-cellular therapy with autologous tumor cell stimulated lymphocyte may be examined as a neo-adjuvant therapy as well as chemotherapy...

..TS-1/CDDP chemotherapy produced a high response in this case, and it may be useful as neoadjuvant chemotherapy for advanced gastric cancer...

..This regimen is a potent treatment for advanced gastric carcinoma, especially when used as preoperative chemotherapy to control cancer cells...

..PR and CR were maintained after 4 courses. There were no remarkable side effects for 4 courses. This chemotherapy may have therapeutic efficacy in cases of advanced gastric cancer with liver and lymph node metastases...

..Regrettably, the patient died one year and 7 months postoperatively. However, we consider the TS-1 and CDDP in combination useful as preoperative chemotherapy for advanced gastric cancer with periaortic lymph node involvement...

..Four weeks after the infusion, CA19-9 had returned to almost normal. We conclude that the combination chemotherapy of 5-FU (or TS-1) and CDDP might be an effective treatment for advanced and metastatic gastric cancer...

..Thus, the chemo-radiation treatment regimen described here may be a potent tool to control advanced gastric carcinoma...

..8% and MST was 523 days. In conclusion, a combination of TS-1 and CDDP for NAC appears to be an effective treatment modality for far advanced gastric cancer patients in view of toxicities, antitumor effects and QOL of the patients...

..Docetaxel will be a key drug for the gastric cancer. In case of responding well to the chemotherapy, we can hope for an extended long-term survival with a continuation of this regimen...

..Histopathologically, resected specimens showed severe fibrosis in most parts of the stomach. Following chemotherapy, the carcinoma was judged to be Grade 2 by histopathological examination...

..Our goal is to pave the way for a strategy in the future that will allow administration of effective therapy, improve safety, and preserve the esophagus in some patients. ..

..Finally, a proven evaluation system is in place to make sure that the Workshop will meet its objectives. ..

..And, finally, a proven evaluation system is in place to demonstrate that the Workshop will meet its objectives. ..

..The use of a new variant of the Pummerer reaction to control both oxidation level and reaction site within the indole nucleus forms the basis of this chemistry. ..

..Aurora kinase has considerable potential to be a very important target in patients' pancreatic cancers, against which new therapeutics can be designed and developed. ..

..The use of a new variant of the Pummerer reaction to control both oxidation level and reaction site within the indole nucleus forms the basis of this chemistry. ..

..Taken together, these studies will introduce new and concise techniques for preparing small polycyclic organic molecules of the type typically sought as pharmaceutical leads. ..

..The search for selective 20S proteosome inhibitors among the Ntn-type proteases will be advanced by these investigations. ..

..We feel this effort, with new approaches to pancreatic cancer, concentrated in a P01, has a chance to make an impact on the disease. ..

..abstract_text> ..

..The results generated from this project therefore have the potential to directly benefit pancreatic cancer patients with improved treatment and the general public with reduced healthcare cost. ..

..The results generated from this project therefore have the potential to directly benefit pancreatic cancer patients with improved treatment and the general public with reduced healthcare cost. ..

..The results generated from this project therefore have the potential to directly benefit pancreatic cancer patients with improved treatment and the general public with reduced healthcare cost. ..

..Finally new strategies for diasteroselective biaryl astropisomer assembly within the context of synthesis efforts directed toward the potent cytotoxic agent diazonamide A will extend current art in this area ..

..abstract_text> ..

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..Successful completion of these syntheses will afford the targets (or analogs) in the most efficient manner to date...