s-1-(combination) and Leukopenia

To evaluate the therapeutic efficacy and safety of S1 monotherapy or combination with nab-paclitaxel for the treatment of elderly patients with metastatic or locally advanced pancreatic adenocarcinoma.. PubMed, Embase, Cochrane Central Library, China Biology Medicine, and China National Knowledge Infrastructure databases were searched without time limits according to the inclusion criteria. RevMan (Version 5.3) software was used for data extraction and meta-analysis. Objective response rate (ORR) and disease control rate (DCR) were used to evaluate therapeutic effects while side effects including leukopenia, thrombocytopenia, neurotoxicity, vomit, and alopecia were extracted for evaluation. There was no need for ethical review in this study because no ethical experiments were conducted and all data used were public data. All relevant data are within the paper and its Supporting Information files.. Four retrospective studies comprising 308 elderly patients with metastatic or locally advanced pancreatic adenocarcinoma were included in the analysis. One hundred fifty-one patients underwent S1 monotherapy and 157 received S1 combined nab-paclitaxel. Meta-analysis indicated that compared with S1 monotherapy, S1 combined with nab-paclitaxel had higher ORR (OR 2.25, 95% CI: 1.42-3.55; P = .0005) and DCR (OR 2.94, 95% CI: 1.55-5.58; P = .0009). The adverse reaction of leukopenia was higher in the combined therapy group (OR 1.85, 95% CI: 1.09-3.13, P = .02), but no significant difference was found in thrombocytopenia, neurotoxicity, vomiting, and alopecia between the 2 groups (P > .05).. Nab-paclitaxel plus S1 was more efficient in terms of ORR and DCR than S1 monotherapy in elderly pancreatic ductal adenocarcinoma patients while the side effect was controllable with a higher probability of leukopenia. Thus, combined nab-paclitaxel and S1 could be safely used in elderly patients.

Topics: Age Factors; Aged; Aged, 80 and over; Albumins; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Drug Combinations; Humans; Leukopenia; Neoplasm Staging; Oxonic Acid; Paclitaxel; Pancreatic Neoplasms; Progression-Free Survival; Tegafur

Two pivotal phase II studies of S-1 in advanced gastric cancer showed response rates of 44% and 49%, and the overall survival time was 207 and 250 days, respectively. The response rate of S-1 exceeded the response rates of other approved drugs, and was comparable to that of combination chemotherapies such as 5-fluorouracil (5-FU) plus cisplatin (CDDP). These data suggested that S-1 could be used as a first-line drug for gastric cancer with a great advantage in quality of life (QOL), because it is an oral drug and can be used at an outpatient clinic. The overall incidences of adverse reactions in the phase II studies were 74.3%, and that of grade 3 or worse were 14.9%. The main adverse reactions were myelosuppression and GI toxicities. As hematological toxicity was more common than other oral fluoropyrimidine derivatives such as UFT, a careful hematological monitoring is necessary. To confirm the survival benefit of S-1 in advanced gastric cancer, a phase III trial of S-1 vs 5-FU vs CDDP plus irinotecan (CPT-11) has been conducted by the Japan Clinical Oncology Group (JCOG), and these results have been awaited. Furthermore, the combination of S-1 with CDDP, CPT-11 or taxane for the treatment of gastric cancer is feasible and active, and phase III studies of S-1 vs several combination therapies including S-1 are also in progress. The effect of S-1 in adjuvant setting is also promising. Currently, a phase III study of surgery alone vs S-1 in patients with a curative resection of gastric cancer has been developed. Further therapeutic benefits are also expected by combining S-1 with other chemotherapeutic agents such as molecular targeted agents.

Topics: Administration, Oral; Anemia; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Cisplatin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Administration Schedule; Drug Combinations; Humans; Irinotecan; Leukopenia; Neutropenia; Oxonic Acid; Quality of Life; Stomach Neoplasms; Stomatitis; Tegafur

The S-1 +biweekly docetaxel (DOC) combination therapy was evaluated for advanced or recurrent gastric cancer patients. This combination therapy was evaluated in vitro using the nude rat-gastric cancer xenograft system. S-1 alone or DOC alone showed antitumor activity, and the antitumor activity was synergistic when two drugs were combined. In clinical settings, the schedule was S-1 80 mg/m2 (day 1-14, orally) and DOC (day 1 and day 15, intravenously) followed by a 2-week rest. In phase I study, the dose of DOC was evaluated, and a recommended dose for phase II was determined as 35 mg/m2. The entry for phase II study was completed, and the preliminary results of 33 patients showed the response rate of 21.2%. The incidence of more than grade 3 adverse effects was 29%(neutropenia, leukocytopenia, anorexia and mucositis). The S-1 +biweekly DOC combination therapy can be a candidate for outpatient chemotherapy for advanced or recurrent gastric cancer.

Topics: Animals; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Docetaxel; Drug Combinations; Humans; Leukopenia; Neoplasm Transplantation; Neutropenia; Oxonic Acid; Quality of Life; Randomized Controlled Trials as Topic; Rats; Rats, Nude; Stomach Neoplasms; Stomatitis; Taxoids; Tegafur

Chemotherapy for colorectal cancer is now improving rapidly due to new drugs like oxaliplatin and molecular targeting drugs. The key drug, however, is still 5-fluorouracil (5-FU). S-1 is an oral 5-FU anti-tumor drug that combines three pharmacological agents: tegafur, 5-chloro-2,4-dihydroxypyridine, which inhibits dihydropyrimidine dehydrogenase activity, and potassium oxonate, which reduces gastrointestinal toxicity. The results of the phase II study suggested that S-1 as a single agent was active against metastatic colorectal cancer: CR rate was 36-40% and MST was about one-year. Toxicity was all tolerable. Clinical trials of S-1 with oxaliplatin or CPT-11 combination chemotherapy are ongoing in Japan. S-1 with molecular targeting drugs will also be studied. Therefore, S-1 is expected to play an important part in chemotherapy for colorectal cancer.

Topics: Administration, Oral; Anorexia; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Clinical Trials, Phase II as Topic; Colorectal Neoplasms; Drug Administration Schedule; Drug Combinations; Fluorouracil; Humans; Irinotecan; Leukopenia; Neutropenia; Oxonic Acid; Survival Rate; Tegafur

A combination therapy of irinotecan hydrochloride (CPT-11) with continuous intravenous infusions of (infusional) 5-fluorouracil (5-FU) and Leucovorin (LV) is often used to treat advanced colorectal cancer. However, recent concerns on safety and convenience have prompted the development of new oral fluoropyrimidine derivatives which improved regimens. Yamada et al conducted a phase I study to assess the maximum tolerated dose and recommended dose of S-1 combined with CPT-11. The study recommended that 150 mg/m2 of CPT-11 be given on day 1 and 80 mg/m2 of S-1 daily on days 1 to 14 every 3 weeks. Recently, several phase I/II studies assessed the efficacy and safety of the combined therapy with S-1 and CPT-11 in patients with advanced colorectal cancer. Some of the studies which were ongoing assessed a tri-weekly schedule regimen. Our results showed that S-1 plus CPT-11 was very effective, with a response rate of 63% and PFS of 8 months. Toxicity was generally mild and manageable on an outpatient basis. The current evidence showed that a combination of S-1 and CPT-11 was more convenient and easier to administer than a combination of CPT-11 plus infusional 5-FU and LV. It will be essential to prove that the combination of S-1 plus CPT-11 can replace the combination of infusional 5-FU and LV plus CPT-11 without negatively affecting efficacy and toxicity.

Topics: Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Colorectal Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Humans; Irinotecan; Leukopenia; Male; Middle Aged; Neutropenia; Oxonic Acid; Remission Induction; Survival Rate; Tegafur

Most cases of head and neck squamous cell carcinoma (HNSCC) are in the advanced stages, resulting in a poor prognosis. To improve the poor outcome, adjuvant chemotherapy is indispensable for advanced cases with a high relapse risk after standard definitive treatments including surgery and/or radiotherapy. To define an adequate administration schedule in adjuvant chemotherapy with S-1, a controlled randomized study in multi-institutes was done. The results showed the 2-week administration followed by 1-week rest was superior to the 4-week administration followed by the 2-week rest in terms of safety and efficacy. In the present paper, some problems of adjuvant chemotherapy were discussed, and the protocol was described in terms of a multi-institutional controlled randomized comparison study of S-1 versus UFT in an adjuvant chemotherapy setting for locally advanced HNSCC.

Topics: Anorexia; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Drug Administration Schedule; Drug Combinations; Head and Neck Neoplasms; Humans; Leukopenia; Multicenter Studies as Topic; Oxonic Acid; Randomized Controlled Trials as Topic; Survival Rate; Tegafur

We report an investigation of the therapeutic efficacy and safety of TS-1 single-agent therapy administered as first-line therapy in 23 cases of unresectable advanced gastric cancer treated at our institution. TS-1 was administered at 80 mg-120 mg (divided into two doses) per day for 28 days followed by a 14-day rest interval, making up a single cycle. The response rate for its antitumor efficacy was 39.1%, with partial response in nine cases, no change in seven cases, progressive disease in five cases, and two cases not evaluable (9 5% confidence interval: 19.7%-61.5%). By site, the response rate was 43.5% for primary tumors (10/23), 33.3% for lymph nodes (3/9), and 16.7% for liver metastasis (1/6). In 1 patient, the carcinomatous ascites disappeared,and in 3 patients they decreased remarkably. No significant differences were observed with regard to age (70 and over/under 70) or histological type (differentiated/undifferentiated). The one-year survival rate was 32.8%, and the 50% survival period was 29 9 days. The most common side effect was leucopenia in seven cases (30.4%), followed by decreased hemoglobin, loss of appetite, hepatic dysfunction and the like. Most side effects, however, were mild and did not exceed grade 2; grade 3 side effects were seen only in two cases (8.7%) of leucopenia and two (8.7%) of hepatic dysfunction, a low rate of occurrence. The outpatient follow-up ratio(outpatient period/total treatment period) was high at 69.6%, meaning that first-line single-agent therapy with TS-1 is beneficial in terms not only of efficacy but also in maintaining quality of life.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemical and Drug Induced Liver Injury; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Male; Middle Aged; Oxonic Acid; Pyridines; Quality of Life; Stomach Neoplasms; Survival Rate; Tegafur

This study aimed to evaluate the feasibility, safety, and efficacy of postoperative adjuvant chemotherapy with docetaxel/cisplatin/S-1 (DCS) following S-1 therapy in patients with stage III gastric cancer after curative gastrectomy.. Patients with stage III gastric cancer who underwent D2 gastrectomy were enrolled. Adjuvant chemotherapy was initiated within 8 weeks of gastrectomy. The first cycle of chemotherapy consisted of S-1 monotherapy (day 1-14), followed by a 7-day rest period. Cycles 2 and 3 consisted of the following: S-1 (day 1-14) administration, followed by a 14-day rest period, and an intravenous infusion of cisplatin and docetaxel on days 1 and 15. After two cycles, S-1 was administered for up to 1 year.. Thirty patients were enrolled between 2014 and 2017. Febrile neutropenia of grade 3 or higher was the most common hematological toxicity with 4 patients (13.3%). Other hematological toxicities of grade 3 or higher were as follows: neutropenia in 3 (10.0%), leukopenia in 3 (10.0%), and anemia in 2 (6.7%) patients. Most frequent non-hematological toxicity of grade 3 was anorexia (n = 4, 13.3%) and general fatigue (n = 3, 10.0%); no grade 4 non-hematological toxicities were observed. Twenty-five patients (83.3%) completed two cycles of DCS treatment and 18 (60.0%) completed subsequent S-1 treatment for 1 year. The relative dose intensity of docetaxel and cisplatin was 0.86 and that of S-1 was 0.88.. The DCS regimen can be acceptable as an adjuvant chemotherapy and offers an effective postoperative treatment option for stage III gastric cancer patients.. UMIN000012785 .. 08/01/2014.

Topics: Adenocarcinoma; Aged; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy-Induced Febrile Neutropenia; Chemotherapy, Adjuvant; Cisplatin; Docetaxel; Drug Administration Schedule; Drug Combinations; Fatigue; Feasibility Studies; Female; Humans; Leukopenia; Male; Middle Aged; Neutropenia; Oxonic Acid; Patient Compliance; Stomach Neoplasms; Tegafur

We conducted a Phase I/II study of carboplatin, S-1 and concurrent thoracic radiotherapy (TRT) for elderly patients (71 years or older) with unresectable stage III non-small cell lung cancer (NSCLC).. Patients received carboplatin (AUC 3-5) on Day 1 and S-1 (30-40 mg/m2 two times daily) on Days 1-14, every 2 weeks, for up to four cycles, plus concurrent TRT at a total dose of 60 Gy. The primary endpoint for the Phase II study was the 1-year progression-free survival (PFS) rate.. Eighteen patients were enrolled in the Phase I study. Febrile neutropenia, a decreased platelet count and esophagitis were dose-limiting toxicities. The recommended doses for the Phase II study were determined to be an AUC of 3 for carboplatin, 40 mg/m2 twice daily for S-1. Twenty-eight patients were evaluated in the Phase II study. The 1-year PFS rate was 57.1% (90% CI 41.6-71.4%), and the median PFS was 16.8 months (95% CI 7.8-not assessable [NA]). The lower limit of the 90% CI for 1-year PFS exceeded the prespecified threshold value of 30%; therefore, the primary endpoint was met. Grades 3-4 toxicities included thrombocytopenia (21%) and hyponatremia (11%). Grade 3 radiation pneumonitis was observed in 18% of patients. No treatment-related deaths were observed.. Combination chemotherapy consisting of carboplatin plus S-1 and concurrent TRT had a promising efficacy in elderly patients with locally advanced NSCLC; however, radiation pneumonitis was frequently observed.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Drug Combinations; Female; Humans; Leukopenia; Lung Neoplasms; Male; Neoplasm Staging; Oxonic Acid; Paclitaxel; Progression-Free Survival; Radiation Pneumonitis; Tegafur; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Combinations; Drugs, Chinese Herbal; Esophageal Neoplasms; Female; Humans; Karnofsky Performance Status; Leukopenia; Male; Nausea; Neutropenia; Oxonic Acid; Tegafur; Vomiting

Gemcitabine (GEM) plus cisplatin (CDDP) chemotherapy has been used worldwide as the standard first-line treatment for advanced biliary tract cancer (BTC). A phase II trial has also suggested promising activity of GEM plus S-1 chemotherapy against advanced BTC. The aim of this study was to evaluate the efficacy and safety of GEM plus S-1 chemotherapy in patients with advanced BTC.. A total of 38 patients were enrolled between August 2008 and November 2011. There were 19 men and 19 women, with a median age of 66 years (range=44-81 years). Seven patients had a previous history of first-line or adjuvant chemotherapy after surgery. The PS was 0 and 1 in 30 and 7 patients, respectively. The treatment response was classified as partial response in 6 patients (15.8%) and as stable disease in 18 patients (47.4%). The median PFS and OS were 5.8 and 15.9 months, respectively. The toxicity was generally mild, and the most common grade 3/4 toxicities were leukopenia (31.6%), neutropenia (36.8%), nausea/vomiting (2.6%), and diarrhea (2.6%). There was one treatment-related death due to interstitial pneumonia.. Our study revealed that gemcitabine plus S-1 chemotherapy was well-tolerated and exhibited favorable antitumor activity in patients with advanced BTC.

Topics: Administration, Intravenous; Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Deoxycytidine; Diarrhea; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Gemcitabine; Humans; Leukopenia; Male; Middle Aged; Nausea; Neutropenia; Oxonic Acid; Tegafur; Treatment Outcome; Vomiting

To compare the short-term efficacy and safety profile of the S-1 + irinotecan + oxaliplatin (TIROX) and docetaxel + cisplatin + flurouracil (DCF) anticancer regimens in patients with advanced gastric cancer.. Patients with recurrent or metastatic gastric cancer diagnosed by pathology were randomly divided into two groups to receive six cycles of either the TIROX regimen (21-day cycle) or the DCF regimen (21-day cycle). After six chemotherapy cycles, the short-term efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumors guidelines and adverse reactions were recorded according to National Cancer Institute Common Toxicity Criteria 2.0 standards.. A total of 60 patients were enrolled in the study. The response rate (complete response + partial response) was significantly higher in the TIROX group (18/30 patients; 60.0%) compared with the DCF group (10/30 patients; 33.3%). The rates of grade III-IV leucopenia and neurotoxicity were significantly higher in the TIROX group than the DCF group.. The TIROX regimen was effective for the treatment of advanced gastric cancer, but it was associated with leucopenia and neurotoxicity.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Docetaxel; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Irinotecan; Leukopenia; Lymphatic Metastasis; Male; Middle Aged; Neurotoxicity Syndromes; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Prospective Studies; Recurrence; Stomach Neoplasms; Taxoids; Tegafur; Treatment Outcome

To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy.. The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months.. Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months, the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS (P=.0019) and OS (P=.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT (P=.0065) and tumor location (P=.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence (P<.0001), which occurred most commonly in the lung.. NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease.

Topics: Adult; Aged; Aged, 80 and over; Agranulocytosis; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemoradiotherapy; Diarrhea; Disease-Free Survival; Dose Fractionation, Radiation; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Leukopenia; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxonic Acid; Rectal Neoplasms; Tegafur; Treatment Outcome

This study aimed to compare the efficacy and toxicity of weekly paclitaxel plus S-1 with weekly paclitaxel plus 5-fluorouracil in treating advanced gastric cancer as first line regimen. The primary end-point was disease control rate (DCR).. Patients with advanced or recurrent gastric cancer were randomly assigned to an experimental arm or a control arm. The experimental arm's dosage schedule was paclitaxel 60 mg/m2 (intravenous infusion) on days 1, 8 and 15 and S-1 80-120 mg/d (oral administration) on days 1-14. Control arm patients were given the same paclitaxel, combined with 5-fluorouracil 500 mg/m2 (continuous intravenous infusion) on days 1-5; and leucovorin 20 mg/m2 (intravenous infusion) on days 1-5. All schedules were repeated every 28 d.. A total of 240 patients were enrolled and equally randomised into two arms. The overall response rate and DCR of the experimental arm was non-inferior to that of the control arm both in the per-protocol set and the full analysis set. The secondary end-point median progression-free survival (PFS) of the experimental and control arms was 153 and 129 d, with the hazard ratio of 0.641 (95% CI: 0.473-0.868, P = 0.004). The hazard ratio of the time to treatment failure of the two arms was 1.449 (95% CI: 0.705-2.980, P = 0.229). The six-month PFS rates of both arms were similar (31.3% versus 31.8%, P = 0.94). Cox regression analysis indicated that only treatment regimen and age were independent predictive factors for PFS. The most common adverse events were haematological and gastrointestinal. The rates of grade 3-4 adverse events were not significantly different between the two study arms and were mostly lower than 5%.. Weekly paclitaxel combined with S-1 is an active and well-tolerated regimen, supporting the view that S-1 can be an alternative for infusional 5-fluorouracil for advanced gastric cancer.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Leucovorin; Leukopenia; Male; Middle Aged; Multivariate Analysis; Nausea; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Treatment Outcome; Young Adult

To determine the efficacy and safety of oral S-1 in combination with cisplatin and thoracic radiotherapy in patients with unresectable stage III non-small-cell lung cancer (NSCLC).. S-1 (50mg/m(2)) was administered orally twice daily for 14 days, with cisplatin (40 mg/m(2)) on days 1 and 8 of each cycle every 3 weeks, for 2-4 cycles. Thoracic radiation therapy was administered in 2 Gy fractions five times weekly for a total dose of 60 Gy. The primary endpoint was the response rate, and secondary endpoints included progression-free survival, overall survival and safety.. Forty-one patients were enrolled in this study. The objective response rate was 87.8% (98% CI: 77.8-97.8%). The median progression-free survival was 467 days (15.4 months), and the median survival time was 904 days (29.7 months). The overall survival rates at 1- and 2-years were 85.7% and 52.9%, respectively. Hematological toxicities included grade 3/4 neutropenia (17%) and grade 3/4 leukopenia (27%). No grade 3 febrile neutropenia was detected, and grade 3/4 non-hematological toxicities were also mild. A grade 3 gastrointestinal hemorrhage was observed in one patient.. The combination of oral S-1 plus cisplatin with concurrent radiotherapy is a promising treatment with a high efficacy and lower toxicity in patients with locally advanced NSCLC.

Topics: Adult; Aged; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Humans; Leukopenia; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Tegafur

To evaluate the efficacy and safety of weekly paclitaxel combined with S-1 or fluorouracil in the first line treatment of advanced gastric carcinoma.. Two hundred and forty patients with untreated advanced gastric carcinoma were randomized into two arms, patients in the experimental arm were given paclitaxel and S-1, while those in the control arm received paclitaxel and fluorouracil. The regimen of experimental arm was paclitaxel 60 mg/m(2) by intravenous infusion, day 1, 8, 15; S-1 80 - 120 mg/day given by oral administration, day 1 - 14. The regimen of control arm was fluorouracil 500 mg/m(2) by intravenous infusion continuously, day 1 - 5; CF 20 mg/m(2) by intravenous infusion, day 1 - 5. The regimens in both arms were repeated every 28 days. The efficacy and safety of both arms were assessed.. Two hundred and twenty-eight patients were analyzed in the full analysis set, and 192 patients were analyzed in per-protocol set (experimental arm 100 patients, control arm 92 patients). The overall response rates of experimental and control arms were 50.0% and 28.3% (P = 0.002), and the disease control rates were 82.0% and 70.7% (P = 0.064), respectively. The primary endpoints of experimental arm were non-inferior to that of the control arm. The secondary endpoint of experimental arm in terms of median progression free survival was significantly better than that of control arm (5 months versus 4 months, P = 0.006). The experimental arm had a higher incidence of grade III-IV bone marrow suppression than the control arm, but the incidence of fever in both arms was not significantly different.. Oral administration of S-1 is an alternative option of venous infusional fluorouracil. Weekly paclitaxel combined with S-1 is a safe regimen and has a promising efficacy.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Diarrhea; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Follow-Up Studies; Humans; Leukopenia; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Paclitaxel; Prospective Studies; Remission Induction; Stomach Neoplasms; Survival Rate; Tegafur

We aimed to validate our hypothesis that a preoperative chemoradiotherapy regimen with S-1 plus irinotecan is feasible, safe, and active for the management of locally advanced rectal cancer in a single-arm Phase II setting.. Eligible patients had previously untreated, locally advanced rectal adenocarcinoma. Radiotherapy was administered in fractions of 1.8 Gy/d for 25 days. S-1 was administered orally in a fixed daily dose of 80 mg/m2 on Days 1 to 5, 8 to 12, 22 to 26, and 29 to 33. Irinotecan (80 mg/m2) was infused on Days 1, 8, 22, and 29. Four or more weeks after the completion of the treatment, total mesorectal excision with lateral lymph node dissection was performed. The primary endpoint was the rate of completing treatment in terms of feasibility. The secondary endpoints were the response rate and safety.. We enrolled 43 men and 24 women in the study. The number of patients who completed treatment was 58 (86.6%). Overall, 46 patients (68.7%) responded to treatment and 24 (34.7%) had a complete histopathologic response. Three patients had Grade 3 leukopenia, and another three patients had Grade 3 neutropenia. Diarrhea was the most common type of nonhematologic toxicity: 3 patients had Grade 3 diarrhea.. A preoperative regimen of S-1, irinotecan, and radiotherapy to the rectum was feasible, and it appeared safe and effective in this nonrandomized Phase II setting. It exhibited a low incidence of adverse events, a high rate of completion of treatment, and an extremely high rate of pathologic complete response.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Diarrhea; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Humans; Irinotecan; Japan; Leukopenia; Lymph Node Excision; Male; Middle Aged; Neoadjuvant Therapy; Neutropenia; Oxonic Acid; Rectal Neoplasms; Tegafur

This phase II study was designed to evaluate the efficacy and safety of oral fluoropyrimidine S-1 plus irinotecan (IRIS regimen) in patients with previously untreated metastatic colorectal cancer.. The response rate was the primary endpoint. Safety, progression-free survival time, and median survival time were secondary endpoints. The subjects were untreated patients with inoperable advanced colorectal cancer. Irinotecan was administered at a dose of 100 mg/m² (on days 1 and 15). S-1 (40 mg/m²) was administered for 2 weeks (on days 1 to 14) and followed by a 2-week rest.. Forty patients were enrolled. Four patients had grade 4 neutropenia, and six patients had grade 3 diarrhea. No other serious hematologic or nonhematologic adverse reactions occurred, and all patients received IRIS safely on an outpatient basis. The response rate was 52.5% (95% confidence interval [CI], 36.1-68.5%). Median progression-free survival was 8.6 months (95% CI, 5.3-11.9), and median survival time was 23.4 months (95% CI, 15.9-30.8).. IRIS produced a high response rate and could be given safely. IRIS may become a first-line treatment for inoperable or recurrent advanced colorectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Drug Combinations; Female; Humans; Irinotecan; Leukopenia; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Tegafur; Treatment Outcome

The aim of this multicenter Phase II study was to assess the efficacy and toxicity of gemcitabine and S-1 combination therapy for metastatic pancreatic cancer.. Chemotherapy-naïve patients with histologically or cytologically proven metastatic pancreatic adenocarcinoma were eligible for this study. Gemcitabine was administered at a dose of 1000 mg/m(2) over 30 min on days 1 and 8, and oral S-1 at a dose of 40 mg/m(2) twice daily from days 1 to 14, repeated every 3 weeks.. A total of 55 patients were included and the efficacy and toxicity were analyzed in 54 patients who received at least one dose of gemcitabine and S-1 combination therapy. Although no complete response was seen, a partial response was achieved in 24 patients, resulting in an overall response rate of 44.4% (95% confidence interval: 30.9-58.6%). The median progression-free survival was 5.9 months (95% confidence interval: 4.1-6.9 months) and the median overall survival was 10.1 months (95% confidence interval: 8.5-10.8 months) with a 1-year survival rate of 33.0%. The major Grade 3-4 toxicities were neutropenia (80%), leucopenia (59%), thrombocytopenia (22%), anorexia (17%) and rash (7%). Hematological toxicity was mostly transient and there was only one episode of febrile neutropenia ≥Grade 3.. Gemcitabine and S-1 combination therapy produced a high response rate with good survival in patients with metastatic pancreatic cancer. A randomized Phase III study to confirm the efficacy of gemcitabine and S-1 combination therapy is ongoing.

Topics: Adenocarcinoma; Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Adenosquamous; Deoxycytidine; Disease-Free Survival; Drug Combinations; Drug Eruptions; Female; Gemcitabine; Humans; Kaplan-Meier Estimate; Leukopenia; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Oxonic Acid; Pancreatic Neoplasms; Tegafur; Thrombocytopenia; Treatment Outcome

We aimed to determine the maximum-tolerated dose (MTD) of S-1 when given with oxaliplatin, to evaluate S-1 pharmacokinetics, and to determine the efficacy and safety of this regimen as a first-line treatment for advanced gastric cancer (AGC).. Oxaliplatin was fixed at a dose of 130 mg/m2 on day 1 (D1). S-1 was administered from D1 to D14 of a 3-week cycle, and escalated by 10 mg/m2 per day from 70 mg/m2 per day up to 100 mg/m2 per day. Pharmacokinetic analyses were performed following a single dose of S-1 on D-5 and D1 of the first cycle.. In phase I (n=18), MTD was not defined. In phase II (n=47) with the planned maximum dose, partial response was achieved in 26 patients (55.3%) and stable disease in 14 patients (29.8%). The median time to progression was 6.6 months (95% CI 4.0-9.2 months) and the median overall survival was 12.5 months (95% CI 9.2-15.9 months). Frequent grade 3/4 toxicities included thrombocytopenia (39%), neutropenia (28%), anemia (17%), and leukopenia (13%). There was one grade 5 febrile neutropenia during the first cycle.. The pharmacokinetics of S-1 was not influenced by oxaliplatin. S-1/Oxaliplatin combination therapy is highly active against AGC and has a favorable toxicity profile.

Topics: Adult; Anemia; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Male; Metabolic Clearance Rate; Middle Aged; Nausea; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Survival Analysis; Tegafur; Thrombocytopenia; Treatment Outcome; Vomiting

To confirm the efficacy and toxicity of gemcitabine and S-1 combination chemotherapy when used as a first-line therapy in patients with unresectable pancreatic cancer.. Patients with locally advanced or metastatic or recurrent pancreatic adenocarcinoma, which was histologically or cytologically proven, with at least one measurable lesion were eligible for the study. Gemcitabine at a dose of 1,000 mg/m2 was intravenously given over 30 min on days 1 and 8, while S-1 at a dose of 40 mg/m2 was orally given twice daily from day 1 to 14, and the cycle was repeated every 3 weeks. The objective response rate, which was assessed according to RECIST criteria, was the primary end point.. A total of 38 patients were enrolled between June 2006 and June 2007. The median number of treatment courses was 5.5 (range 1-22). Thirty-four patients were evaluable for response. Although no complete response was seen, partial responses were achieved in 11 patients, resulting in an overall response rate of 32% [95% confidence interval (CI) 17-48%]. The median response duration was 6.0 months (95% CI 4.6-8.3 months), the median time-to-progression was 5.4 months (95% CI 2.9-8.0 months), and the median overall survival was 8.4 months (95% CI 5.7-11.1 months). The major grade 3/4 hematologic toxicities were neutropenia (39.5%), leukopenia (15.8%), thrombocytopenia (2.6%), and anemia (7.9%). The major grade 3/4 non-hematologic toxicities included anorexia (10.5%), stomatitis (2.6%), rash (7.9%), fatigue (7.9%) and hyperbilirubinemia (5.3%).. Gemcitabine and S-1 combination chemotherapy was effective and tolerable in patients with unresectable pancreatic cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Combinations; Fatigue; Female; Gemcitabine; Humans; Kaplan-Meier Estimate; Leukopenia; Male; Middle Aged; Nausea; Neutropenia; Oxonic Acid; Pancreatic Neoplasms; Tegafur; Treatment Outcome

To evaluate the efficacy and safety of gemcitabine and S-1 combination chemotherapy in patients with advanced biliary tract cancer.. Patients with a measurable lesion and no previous history of chemotherapy or radiotherapy were enrolled. Gemcitabine was administered intravenously at a dose of 1,000 mg/m(2) over 30 min on day 1 and 15, repeated every 4 weeks. S-1 was administered orally at a dose of 40 mg/m(2) b.i.d. on days 1-14. Tumor response was assessed every two cycles using Response Evaluation Criteria in Solid Tumors criteria.. As much as 35 patients were enrolled between December 2006 and July 2008; 14 patients (40%) with gallbladder cancer and 14 (40%) with intrahepatic cholangiocarcinoma were included and 7 patients (20%) had received previous surgical resection. The overall response rate was 34.3% and the overall disease control rate was 82.9%. The median overall survival time was 11.6 months (95% CI, 7.3-15.6 months), and the median time to progression was 5.9 months (95% CI, 4.0-7.7 months). The grade 3/4 toxicities were leucopenia (23%), neutropenia (34%), anemia (20%), thrombocytopenia (6%) and anorexia (3%).. Gemcitabine and S-1 combination chemotherapy has promising efficacy and good tolerability in patients with advanced biliary tract cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Leukopenia; Male; Middle Aged; Nausea; Neutropenia; Oxonic Acid; Survival Analysis; Tegafur; Treatment Outcome

This prospective multicenter phase II study was carried out to investigate the efficacy, safety and pharmacokinetics of S-1 monotherapy in elderly patients over 75 years of age, with unresectable advanced or recurrent gastric cancer.. Patients had measurable or evaluable lesions according to the Japanese Classification of Gastric Carcinoma. S-1 (25-60 mg determined by the body surface area and creatinine clearance) was given orally, twice daily. A course of treatment consisted of 4-week administration followed by a 2-week rest period, and the patients received repeated courses.. Thirty-three patients were enrolled. Pharmacokinetics of S-1 was studied in six patients, and the maximum plasma concentrations of respective metabolites after S-1 administration were found to be similar to those reported for younger cancer patients. The overall response rate in 33 patients was 21.2% (95% CI, 10.7-37.8%), and median progression-free survival was 3.9 months, with a median overall survival of 15.7 months. Frequently noted adverse events include leukopenia, neutropenia, anemia, anorexia, and fatigue. As for serious adverse events, relatively higher frequencies of anemia (9%) and anorexia (12%) of grade 3 severity were found, but there were no grade 4 episodes.. The results suggest that S-1 monotherapy is safe and useful for elderly patients with unresectable advanced or recurrent gastric cancer when the dose is selected with caution, taking into account renal function.

Topics: Aged; Aged, 80 and over; Anorexia; Antimetabolites, Antineoplastic; Drug Combinations; Fatigue; Female; Humans; Leukopenia; Male; Metabolic Clearance Rate; Neutropenia; Oxonic Acid; Prospective Studies; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

The purpose of the present phase II study was to evaluate both the efficacy and toxicity of the combination of S-1 and docetaxel in previously treated patients with locally advanced or metastatic non-small cell lung cancer.. Thirty-eight previously treated patients with non-small cell lung cancer were treated with S-1 (80 mg/m(2), days 1-14, oral) and docetaxel (40 mg/m(2), day 1, intravenous) every 3 weeks.. No complete response was observed, and seven patients had a partial response, yielding an overall response rate of 18.4% (95% CI, 7.7-34.3%). The median overall survival time and 1-year overall survival rate were 16.1 months and 60%, respectively. The median progression-free survival time was 4.4 months. Myelosuppression was the main toxicity with grade 3 or 4 neutropenia and leukopenia in 50 and 21%, respectively. There was no irreversible toxicity in this study.. The combination of S-1 and docetaxel is well tolerable and has substantial activity for patients with locally advanced or metastatic non-small cell lung cancer. A phase III trial comparing docetaxel with or without S-1 would warrant further investigation.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Humans; Leukopenia; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Oxonic Acid; Survival Rate; Taxoids; Tegafur; Treatment Outcome

Although S-1 is effective against advanced gastric cancer (AGC), its efficacy in elderly patients has not yet been investigated sufficiently. We assessed the efficacy and safety of S-1 monotherapy in elderly patients with AGC.. We conducted a retrospective review of the data of 153 patients with unresectable/recurrent gastric adenocarcinoma who received S-1 monotherapy as first-line chemotherapy at our institution. S-1 was administered orally twice daily at the dose of 40 mg/m², on days 1-28, every 6 weeks. We categorized the patients into three groups, the young (≤65 years old), the middle-aged (66-75 years old), and the elderly (≥76 years old); and the drug toxicity, objective responses, progression-free survivals, and overall survivals were compared among the three groups.. The incidence of leukopenia of grade 3 or greater in the three groups was 7%, 5%, and 13%, and that of anemia was 9%, 18%, and 27%, respectively. In regard to nonhematological toxicities, the incidence of nausea of grade 3 or greater was 3%, 5%, and 13%; that of fatigue was 5%, 11%, and 20%; and that of anorexia was 5%, 6%, and 27%, respectively. As for the treatment efficacy, the objective response rates, median progressionfree survivals, and overall survivals in the young, middle-aged, and elderly groups were 53%, 46%, and 33%; 7.8, 5.6, and 3.9 months; and 16.9, 17.1; and 7.7 months, respectively.. Although S-1 monotherapy showed moderate efficacy in elderly (≥76 years) patients with AGC, patients in this age group showed higher incidences of severe toxicities than the younger patients.

Topics: Adenocarcinoma; Administration, Oral; Age Factors; Aged; Aged, 80 and over; Anemia; Anorexia; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Administration Schedule; Drug Combinations; Fatigue; Female; Humans; Leukopenia; Male; Middle Aged; Nausea; Neoplasm Recurrence, Local; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

We conducted a phase I study to determine the maximum tolerated dose, the recommended dose and the safety profile of S-1 and gemcitabine combination regimen in the treatment of elderly patients (> or = 70 years) with advanced nonsmall cell lung cancer (NSCLC). Chemotherapy-naive patients with advanced NSCLC were treated with S-1 and gemcitabine. S-1 was administered orally twice daily for 14 days and gemcitabine on days 1 and 15 of each cycle, and this was repeated every 4 weeks. Doses of each drug were planned as follows: level 1, 800/60; level 2, 1000/60; level 3, 1000/70; and level 4, 1000/80 [gemcitabine (mg/m2/ day)/S-1 (mg/m2/day)]. The dose-limiting toxicity (DLT) of the regimen was assessed during the first chemotherapy cycle. Sixteen patients were enrolled in this study. The main grade 3 toxicities observed during the first cycle were neutropenia (43.7%), leukopenia (18.7%), and hyperglycemia. One of six patients in level 3 had DLT. Although no patients in level 4 experienced DLT, this level was considered the maximum tolerated dose. Level 4 was selected as the recommended dose. Objective responses were seen in four patients (response rate, 42.9%). The combination of S-1 plus gemcitabine is a feasible and well-tolerated regimen for the treatment of elderly patients with advanced NSCLC.

Topics: Administration, Oral; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Deoxycytidine; Dose-Response Relationship, Drug; Drug Combinations; Female; Gemcitabine; Humans; Hyperglycemia; Leukopenia; Lung Neoplasms; Male; Maximum Tolerated Dose; Neutropenia; Oxonic Acid; Tegafur; Treatment Outcome

The safety of chemotherapy combining TS-1 and weekly paclitaxel for the treatment of unresectable and recurrent gastric cancer was evaluated in this study. Paclitaxel was administered by intravenous drip infusion at a starting dose (level 1) of 50 mg/m2 on days 1, 8, and 15. TS-1 was administered orally at a dose of 40 mg/m2twice a day for 2 weeks (days 1-14) followed by 2 weeks rest. A total of 9 patients were enrolled in this study. Two out of 6 patients treated with level 1 suffered from leukocytopenia and neutropenia, which were determined as dose-limiting toxicity (DLT). Three patients were treated with level 2, in which the dose of paclitaxel was increased up to 60 mg/m2. One of 3 patients suffered from grade 3 diarrhea and one patient from grade 4 leukocytopenia, eutrocytopenia, anemia, and stomatitis, which were determined as DLT. According to these results,level 1 of this regimen was recommended as a safe treatment for gastric cancer patients. A phase II study will be performed to evaluate the efficacy of the combination chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Male; Middle Aged; Neutropenia; Oxonic Acid; Paclitaxel; Pyridines; Stomach Neoplasms; Tegafur

A 67-year-old man was admitted to our hospital, complaining of productive cough and chest pain. Chest radiograph and computed tomography revealed a huge mass invading the mediastinum, enlargement of right hilar and cardiophrenic lymph nodes and nodules in right lower lobe and left upper lobe. Multiple space occupying regions in the liver were also observed. Cytology for exfoliated sputum revealed adenocarcinoma, so he was diagnosed with advanced lung cancer (clinical stage T 4 N 2 M 1, stage IV). He was enrolled in a clinical phase II study, and received combination chemotherapy with TS-1 and cisplatin. TS-1 was administered on days 1-21. Cisplatin was administered on day 8. Every cycle was repeated every 5 weeks. The patient then received 6 cycles of chemotherapy,and yielded a partial response (87% decrease in size determined by RECIST criteria version 2. 0). Grade 2 leukopenia and neutropenia were observed, and non-hematologic toxicities were also mild. The disease progressed after the end of chemotherapy, and he was given 5 regimens of chemotherapy, including gefitinib. He died of brain metastases. Time to progression of his disease for combination chemotherapy using TS-1 and cisplatin chemotherapy was 240 days. Survival time was 709 days. This combination chemotherapy was effective in the present case, and might prolong survival. We think it is valuable to confirm the efficacy of TS-1 and cisplatin combination chemotherapy.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cisplatin; Drug Administration Schedule; Drug Combinations; Humans; Leukopenia; Lung Neoplasms; Male; Neutropenia; Oxonic Acid; Pyridines; Tegafur

Multimodality therapy incorporated with radiotherapy, surgery and chemotherapy are used in the treatment of head and neck cancer in order to improve the local control and survival rate. TS-1, a newly developed oral antitumor agent which could achieve the same therapeutic concentration as that of 5-FU under continuous and intravenous treatment, has been used as adjuvant therapy for carcinomas in recent years. We presented our experience applying a new regimen of TS-1 and its side effects. TS-1 has been applied for head and neck carcinomas since 2001. The oral application of TS-1 has been used in 32 cases of head and neck cancer in our department since 2003, and the agent has been applied in 22 of 32 cases as adjuvant therapy. The primary sites of malignancy included hypopharyngx (7 cases), larynx (6 cases), maxillary sinus (2 cases), oropharynx (2 cases), oral cavity (4 cases), submandibular gland (1 case) and one case in which the primary site was unknown. A regimen of four-week application followed by two-week rest had been used in 6 cases in the first part of this trial. However, a high frequency of blood toxicity was found from the third week, requiring alteration of the protocol. Thus, a new regimen of two-week application followed by one week rest was thereafter used in the other 16 cases. Blood toxicity was found in 66.7% of those cases receiving a four-week application followed by two-week rest regimen. In the 16 cases receiving the two-week application followed by one-week rest regimen, only one case showed grade 2 leucopenia while continuous application for more than eight weeks was possible in 9 cases. Mild macrocytic anemia was found in some of these cases, however none of which required any necessary interruption of the treatment. Side effects other than blood toxicity, such as edema or pigmentation of lower limbs, erythema of skin and diarrhea, were found in the other cases, requiring suspension of the treatment. But the subsequent application was possible after a break or decreasing the dosage. We concluded that the new regimen of two-week application followed by one-week rest is less likely to be interrupted by the side effects and is safer to be used outpatiently, compared with the four-week application followed by two-week rest.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anemia, Megaloblastic; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Administration Schedule; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Leukopenia; Male; Middle Aged; Oxonic Acid; Pyridines; Tegafur

In the present article, we have summarized the phase I/II clinical trials on combination therapy of S-1 and docetaxel. With result of the phase I study, patients were treated with intravenous infusion of 40 mg/m2 docetaxel on day 1 and oral S-1 80 mg/m2/day on days 1 to 14 every 3 weeks. Forty eight patients received a total of 272 treatment cycles. No complete responses (CRs) and 27 partial responses (PRs) were observed for an overall response rate (CR+PR) of 56.2% (95% CI, 38-66%). Eighteen patients (37.5%) had stable disease (SD), and 3 patients (6.2%) had progressive disease (PD) as best response. The tumor control rate (CR+PR+SD) was 93.8% (95% CI, 83-98%). The median overall survival was 14.3 months (95% CI: 10.7-20.3 months) and the median time to tumor progression was 7.3 months (95% CI: 4.2-10.7 months). The most common grade 3-4 hematologic toxicities were neutropenia 58.3%, leukopenia 41.7%, febrile neutropenia 8.3%, and anemia 8.3%. The most common grade 3 nonhematologic toxicities were anorexia 14.6%, stomatitis 8.3%, nausea 6.3%, diarrhea 4.2%, constipation 4.2%, and vomiting 2.1%. No grade 4 nonhematologic toxicities were reported, and all treatment-related toxicities were resolved. The mechanisms underlying these synergistic effects of S-1 and docetaxel were examined by expression and activity analyses of 5-FU metabolic enzymes. The expressions of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) were decreased and that of orotate phosphorybosyl transferase (OPRT) was increased in mRNA, protein level and activity assay after the treatment with docetaxel and 5-FU in the TMK-1 gastric cancer cell. These findings strongly indicate that the combination chemotherapy of docetaxel and S-1 is effective against gastric carcinomas and therefore is a good candidate as a standard chemotherapeutic strategy in treating these tumors.

Topics: Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Administration Schedule; Drug Combinations; Humans; Infusions, Intravenous; Leukopenia; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur

In the present article, we report the results of phase I/II combination chemotherapy study of biweekly paclitaxel and S-1 administration in patients with advanced gastric cancer. In the phase I study, we could determine the recommended dose for the phase II study with paclitaxel and S-1 to be 120 mg/m2 and 80 mg/m2, respectively. The side effect was not so severe. The overall response was 53%. In conclusion, biweekly paclitaxel and S-1 administration can be safely combined for the treatment of advanced gastric cancer. This combined therapy represents a novel and active treatment regimen with low toxicity and can be defined as safe and effective. Now we are analyzing the result of the phase II study.

Topics: Administration, Oral; Adult; Aged; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Humans; Infusions, Intravenous; Leukopenia; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Paclitaxel; Quality of Life; Stomach Neoplasms; Tegafur

We planned to conduct a phase II clinical study of combination therapy with CPT-11 and S-1. The antitumor effect was the primary endpoint, while the safety, progression-free survival time, and median survival time were the secondary endpoints. The subjects were untreated patients with inoperable advanced colorectal cancer aged 20-75 years. Based on the results of our previous phase I/II study in patients with gastric cancer, the dosage was established in consideration of safety for outpatient therapy. CPT-11 was administered at a dose of 100 mg/m2 (on days 1 and 15) as an intravenous infusion over 90 minutes, and oral S-1 (40 mg/m2) was administered after breakfast and dinner and then withdrawn for 2 weeks. No other serious adverse reactions occurred (either hematological or non-hematological), and all patients could receive therapy safely on an outpatient basis. Interim analysis suggested excellent results, with a response rate of 50%. Combination therapy with CPT-11 and S-1 achieved a high response rate and could be given safely. These findings suggest that the therapy has potential as first-line treatment for inoperable advanced recurrent colorectal cancer.

Topics: Administration, Oral; Adult; Aged; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Drug Administration Schedule; Drug Combinations; Humans; Infusions, Intravenous; Irinotecan; Leukopenia; Middle Aged; Nausea; Neutropenia; Oxonic Acid; Remission Induction; Tegafur

Various kinds of combination chemotherapies with 5-FU as a base agent have been performed for patients with advanced or recurrent colorectal cancer. S-1 was a newly developed 5-FU derivative and was orally administered. One of the combination therapies with S-1 plus irinotecan (CPT-11) has also been expected to have a better therapeutic value. Recently this combination therapy has been undertaken by our department, and its clinical use and toxicities are described in this article.

Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Drug Administration Schedule; Drug Combinations; Humans; Infusions, Intravenous; Irinotecan; Leukopenia; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Tegafur; Vomiting, Anticipatory

We conducted a phase I study to determine a recommended dose (RD) of S-1 for chemo-radiotherapy consisting of S-1+ radiotherapy for T 2 N 0 larynx cancer. The method of administration used to assess the RD was irradiation with 2 Gy/day for 5 days a week until a total dose of 60 Gy, and concomitant administration of S-1 once a day for 2 weeks beginning on the day therapy was started followed by 2 weeks off the drug and 2 weeks on the drug with the dose escalating from S-1 60 mg/body/day (level 1) to 80 mg/body/day (level 2), and then to 100 mg/body/day (level 3). 18 patients were enrolled. 4 patients developed an adverse event of grade 3 radiation dermatitis which became a dose-limiting toxicity (DLT) at level 3. We then concluded that 100 mg/body/day was the maximum tolerated dose (MTD) of S-1 and decided that the RD of S-1 was 80 mg/body/day.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Combined Modality Therapy; Deglutition Disorders; Drug Administration Schedule; Drug Combinations; Female; Glottis; Humans; Laryngeal Neoplasms; Leukopenia; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Radiation Injuries; Radiodermatitis; Radiotherapy Dosage; Stomatitis; Tegafur

The standard care for unresectable locally advanced head and neck cancer (HNC) is concurrent chemoradiotherapy (CRT). Although there is no standard regimen of CRT, a platinum-based regimen has shown a better survival benefit than other regimens. The control arm in a randomized trial for unresectable locally advanced HNC is radiotherapy concurrent with CDDP (100 mg/m2, every 3 weeks), which has been considered to be too toxic for clinical practice in Western countries and has required frequent dose modifications. Because the Japanese also have been considered unable to tolerate this regimen, no prospective study of it has been conducted in Japan. Most Japanese patients with locally advanced head and neck cancer have received concurrent chemoradiotherapy with 5-FU and CDDP (70-80 mg/m2). S-1 has shown high activity in HNC with a response rate of 34%. Furthermore, a combination of cisplatin and S-1 therapy for HNC has been reported to have good efficacy. With this rationale in mind, we conducted a phase I study of CRT with S-1 and CDDP for unresectable locally advanced squamous cell carcinoma of the head and neck. The CR rate was very promising, though preliminary, and warrants further investigation. The Japan Clinical Oncology Group (JCOG) is planning a multicenter phase II study of concurrent chemoradiotherapy with S-1 and CDDP for locally advanced unresectable HNC.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Deglutition Disorders; Drug Administration Schedule; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Leukopenia; Male; Middle Aged; Neutropenia; Oxonic Acid; Radiation Injuries; Radiodermatitis; Radiotherapy Dosage; Tegafur

We investigated preoperative chemotherapy with S-1 and low-dose cisplatin for the untreated stage II-IV oral squamous cell carcinoma patients. The chemotherapy consisted of S-1 80 mg/m2/day (day 1-14) and CDDP 5 mg/m2/day (day 1-5 and day 8-12) intravenous drip (less than 1 hour). In the second phase clinical trial of 44 patients, the clinical response rate was 63.7% and the histological response rate by the Oboshi-Shimosato's evaluation was 61.4%. The main adverse events were myelosuppression and gastrointestinal disturbance such as nausea 36.4%, anorexia 27.3%, neutropenia 25% and leukopenia 25%. Grade 3 and 4 adverse events were neutropenia 11.4%, leukopenia 9.1%, thrombocytopenia 4.5% and oligochromemia 4.5%. The two-year overall survival rate was 92.6%. The advantages of this chemotherapy are high response rate, low adverse effects and not to prevent planned therapies such as surgery and radiation. These facts suggest that this chemotherapy is suitable for preoperative chemotherapy.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Humans; Infusions, Intravenous; Leukopenia; Male; Middle Aged; Mouth Neoplasms; Nausea; Neutropenia; Oxonic Acid; Preoperative Care; Survival Rate; Tegafur

The therapy 5-FU and CDDP with radiation is thought to be the standard therapy for esophageal cancer patients by now. However, the therapy is associated with a comparatively high incidence of gastrointestinal disorders and requires hospitalization. We have proposed a new regimen of Docetaxel and TS-1 with radiation for maintaining of QOL and improving outcome. Step 1 of the clinical phase I/ II study was conducted for 10 cases from May 2004 to March 2006. Treatment could be accomplished in all cases, and no treatment-related deaths or adverse events of grade 4 were observed in any case. As for hematotoxicity, one case had leucopenia of grade 3 and neutropenia of grade 2. As for non-hematotoxic adverse events, anorexia of grade 3 was recognized in one case of level 3. The response rate evaluated by RECIST was 66% (CR in 2 cases, PR in 4 cases), and the rate based on the Guide Lines for the Clinical and Pathologic Studies on Carcinoma of Esophagus by the Japanese Society for Esophageal Cancer was 70% (CR in 3 cases, PR in 4 cases). We assumed that the recommended dosage of TXT was 30 mg/m(2) and that of TS-1 was 60 mg/m(2) with radiotherapy of 60 Gy. This combination therapy may be recommended because of fewer adverse events and a higher responsive rate than the standard therapies. We intend to continue this study to step 2 and 3, and to reveal the response rate and adverse events for more esophageal cancer patients.

Topics: Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Docetaxel; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Humans; Leukopenia; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Radiotherapy Dosage; Radiotherapy, Adjuvant; Taxoids; Tegafur

The safety of chemotherapy combining TS-1 and pirarubicin (THP) for treatment of recurrent or locally advanced gastric cancer was evaluated. THP was administered by intravenous drip infusion at a dose of 14 mg/m2 every other week. TS-1 was administered orally at a dose of 40 mg/m2 twice a day for 2 weeks followed by 2 weeks of rest (level 1), for 3 weeks followed by 2 weeks of rest (level 2), and for 4 weeks followed by 2 weeks of rest (level 3). Three patients were treated with the level 1 schedule. One patient with peritoneal dissemination received 22 courses of the treatment, and benefited from a long-term NC. However the remaining 2 cases were diagnosed as PD after 4 courses and were withdrawn from further treatment. Two patients in this group suffered from grade 2 adverse events according to the NCI-CTC. Only 1 patient who had liver metastasis was treated at level 2. Fourteen courses were administered, and a PR was achieved while grade 2 adverse events were observed. One of 3 patients who were treated with level 3 had grade 3 adverse events. Consequently, 3 more cases were added to this dose level, and no additional grade 3 adverse events were observed, while grade 2 adverse events were seen in 4 cases. Urinary urgency had completely disappeared in 1 patient with peritoneal recurrence. Myelosuppression, which was the main observed adverse event, was well controlled and of brief duration. The response, including alleviation of clinical symptoms, was confirmed in 3 of 5 chemo-naive patients.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Liver; Male; Middle Aged; Nausea; Neoplasm Recurrence, Local; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur; Vomiting, Anticipatory

A phase I/II clinical trial has been planned to evaluate the safety and efficacy of combination therapy of S-1 with low-dose cisplatin in patients with unresectable or recurrent gastric cancer. A new statistically as well as clinically deliberated study design is applied to determine the maximal benefits of combination chemotherapy. This trial uses a 'continual reassessment method' for evaluating toxicity and a "two-stage method" for assessing the response rate to determine the combination that achieves adequate tumor response without toxicity in a high proportion of patients. Three specialized institutions will recruit 10-16 patients for the phase I part of the trial, and 14 institutions, in conjunction with the three specialized ones, will enroll 42 patients for the phase II part. The goal of this trial is to establish a useful chemotherapeutic treatment in an outpatient setting.

Topics: Administration, Oral; Adult; Aged; Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur; Thrombocytopenia

A late phase II clinical study of S-1 against advanced or refractory breast cancer was done by 37 institutes in Japan. S-1 was administered twice daily at 80, 100 or 120 mg/body/day consecutively for 28 days followed by 14 days of rest (1 course). Eighty-three patients were enrolled and 81 were eligible for the study. The response ratio was 42.0% with 6 CR and 28 PR and its 95% confidence interval for the response was 31.1 to 53.5%. The median survival period was 910 days (95% confidence interval was 493-1, 083 days). The observed major adverse reactions (> or = grade 2) were as follows: hematological toxicities: leukopenia 21.0% (17/81), neutropenia 28.4% (23/81), erythropenia 4.9% (4/81); gastrointestinal toxicities: anorexia 9.9% (8/81), nausea and vomiting 12.3% (10/81), diarrhea 8.6% (7/81), stomatitis 1.2% (1/81), and fatigue 8.6% (7/81). The severe adverse reactions (> or = grade 3) were as follows; hematological toxicities: neutropenia 8.6% (7/81), anorexia 4.9% (4/81), fatigue 3.7% (3/81), nausea and vomiting 1.2% (1/81), diarrhea 1.2% (1/81), stomatitis 1.2% (1/81). Grade 4 adverse reactions (neutropenia and fatigue) were observed only in 1 patient. The ratio without hospitalization was 87.7%. These results strongly suggest the superior efficacy and safety of S-1 against patients suffering from advanced, refractory breast cancer. 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.

Topics: Adult; Aged; Anorexia; Antimetabolites, Antineoplastic; Breast Neoplasms; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Middle Aged; Nausea; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Pyridines; Tegafur; Vomiting, Anticipatory

The efficacy and safety of the oral fluoropyrimidine TS-1, which contains a dihydropyrimidine dehydrogenase (DPD) inhibitor, were examined in fifty-five patients with gastric cancer. The patients were divided into 28 with measurable cancer lesions (TUM group) and 27 without them (ADJ group). The total number of courses was 164 (mean: 5.9 courses) in the TUM group and 146 (mean; 5.4 courses) in the ADJ group. The response rate in the TUM group, excluding three patients who could not be evaluated because of incomplete administration, was 40% (CR: 4, PR: 6, NC: 6, PD: 9). Among responders, the mean number of courses to response was 2.2 and the median survival time (MST) was 21.7 months. In terms of safety, adverse reactions appeared in forty-five patients (82%) and the incidence was higher in the ADJ group. Major toxicities were leukopenia (38%), anorexia (27%), increased total bilirubin concentration (25%) and diarrhea (24%). Adverse reaction of grade 3 was found in only three patients (5.5%) and there were no drug-related deaths. In conclusion, TS-1 is safe and effective if attention is given to biweekly examinations for the development of adverse reactions.

Topics: Administration, Oral; Adult; Aged; Anorexia; Antimetabolites, Antineoplastic; Bilirubin; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Postoperative Period; Pyridines; Stomach Neoplasms; Tegafur

An early phase II clinical study of S-1 in patients with advanced or recurrent breast cancer was undertaken by a cooperative study group (Breast Cancer Working Group) of 14 institutes in Japan. S-1 was administered twice daily at 75 or 50 mg (dose FT)/body for 28 consecutive days with 14 days rest (one course). Twenty-eight patients were enrolled, 27 were eligible for the study, and 25 were evaluable for efficacy. Four complete responses and seven partial responses were obtained, and the response rate was 40.7% (11/27) [ninety percent confidence interval for this response was 26.7-56.4%]. The major adverse reactions observed were myelosuppression represented by leukopenia 44.4% (12/27), neutropenia 40.7% (11/27), RBC decreased 37.0% (10/27), hemoglobin decreased 29.6% (8/27), anorexia 55.6% (15/27), nausea/vomiting 48.1% (13/27), and fatigue 33.3% (13/27). The results suggested that the efficacy and safety of S-1 were effective against advanced or recurrent breast cancer. The objective of study judged should be investigated in a late phase II clinical study.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Breast Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Pyridines; Remission Induction; Survival Analysis; Tegafur

In developing new anticancer agents, the most important thing is the balancing of antitumor activity and toxicity. To achieve high activity and low toxicity, S-1 was designed, in which tegafur, prodrug of 5-FU, was combined with two classes of modulators. CDHP, inhibitor of 5-FU degradation in liver and Oxo, inhibitor of 5-FU phosphoribosylation in digestive tract, respectively. This cooperative study with 15 nation-wide institutes was conducted to evaluate the antitumor activity and toxicity of S-1 in patients with advanced head and neck cancer from Jan. 1994 to March 1996 in Japan. Out of 26 patients, CR was achieved in 1 and PR in 11 with a response rate of 46.2%, while adverse events of grade 3 were as follows: hemoglobinemia (7.7%), leukocytopenia, neutropenia, stomatitis and anorexia (3.8%), each. Neither grade 4 adverse event nor treatment-related deaths were observed. Based on these findings, it was concluded that S-1 is a useful anticancer agent with the low grade toxicities for treatment of the patients with advanced head and neck cancer, and the effects of CDHP and Oxo found in preclinical studies might be also reflected in these results.

Topics: Administration, Oral; Adult; Aged; Anorexia; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Leukopenia; Lymphatic Metastasis; Male; Middle Aged; Neutropenia; Oxonic Acid; Pyridines; Stomatitis; Tegafur

The purpose of this study was to clarify the efficacy and safety of docetaxel and cisplatin as second-line treatment for patients with S-1 refractory advanced gastric cancer. Between 1999 and 2006, 32 patients received docetaxel (60 mg/m²) and cisplatin (60 mg/m²) (Dp regimen) on day 1 every 3 weeks. This regimen was repeated at least three times at 3-week intervals until disease progression or unacceptable toxicity was detected. The overall response rate was 21.9%. Seven patients showed partial response, 17 showed stable disease and 8 showed disease progression. The median survival time was 12.3 months after the start of the first-line treatment. The median survival time and time to progression following the DP regimen was 7.8 months and 4.0 months, respectively. The major adverse effects were leukopenia and neutropnea. Non-hematological toxicities were generally mild to moderate and controllable. this study showed satisfactory therapeutic outcomes for patients with gastric cancer refractory to S- 1 chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease Progression; Docetaxel; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Leukopenia; Male; Middle Aged; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur; Watchful Waiting

The efficacy of S-1 as part of a 2nd/3rd-line therapy in cases of advanced recurrent colon cancer was studied.. The efficacy of treatment with S-1 (initial dosage: 80 mg/m(2)) was studied in 19 patients with advanced recurrent colon cancer in whom PD was observed after pretreatment with 5-FU-based combination chemotherapy had been performed during the period from December 2003 to April 2006. Patients who underwent a course that exceeded 1 month after the pretreatment and who met the criteria for the appropriate use of S-1 were selected as subjects.. The median age was 65 years (45 to 75 years old) with 10, 6, and 3 patients having a PS score of 0, 1, and 2, respectively, and the details of the duration of the pretreatment was that 12 and 7 patients respectively received 2nd-and 3rd-line therapy. The median duration of the treatment with S-1 was 141 days, and the number of subjects with PR, SD, and PD who underwent S-1 treatment was 2, 7, and 6, respectively, with a response rate of 13. 3% and a disease control rate of 60. 0%. The progression free survival time and the overall median survival time were 5. 4 months and 13. 9 months, respectively. Regarding the effectiveness according to treatment line, particularly in the subjects who were administered S-1 as part of the 2nd-line therapy, good results were observed, thus showing a response rate of 20% and an overall median survival time of 13. 9 months, which exceeded 1 year. The incidence of adverse events was 58%(11 and 19), and the major side effects were neutropenia in 31. 6% (6 and 19) and leukopenia in 21. 1% (4 and 19) of the patients, which are both mild and showed a grade of 2 or lower.. The use of S-1 as part of a 2nd/3rd-line therapy in cases of advanced recurrent colon cancer may contribute to good prognoses.

Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Disease Progression; Drug Combinations; Female; Humans; Japan; Leukopenia; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Prognosis; Recurrence; Salvage Therapy; Survival Rate; Tegafur

To the authors' knowledge, there is no effective therapy for extrahepatic metastasis of hepatocellular carcinoma (HCC). In a pilot study, the results of combination therapy of S-1, a novel oral dehydropyrimidine dehydrogenase (DPD) inhibitor, and interferon-alpha (IFN-alpha) are reported for HCC patients with extrahepatic metastasis.. Twelve patients with extrahepatic metastasis of HCC were enrolled in the pilot study. S-1 was administered orally at a dose based on body surface area, twice daily after a meal, for 4 weeks. IFN-alpha was injected subcutaneously on Days 1, 3, and 5 of each week. One course consisted of consecutive administration for 28 days followed by 14 days rest.. An objective response was observed in 3 (25%) of 12 patients. The overall 1-year survival rate was 61.7%. Grade 3 leukocytopenia was observed in 1 patient (8.3%). No severe toxicity or treatment-related deaths were observed.. The combination therapy of S-1 and IFN-alpha appears to be highly efficacious, with low toxicity in patients with extrahepatic metastases of HCC. The combination chemotherapy of oral S-1 and subcutaneous IFN-alpha is a potentially promising treatment strategy for advanced HCC with extrahepatic metastasis.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Female; Follow-Up Studies; Humans; Immunologic Factors; Injections, Subcutaneous; Interferon-alpha; Leukopenia; Liver Neoplasms; Male; Middle Aged; Oxonic Acid; Pilot Projects; Remission Induction; Survival Rate; Tegafur; Thrombocytopenia

The present study evaluated the efficacy and safety of nedaplatin-combination therapy (NDP/5-FU [5-FU arm] or NDP/S-1 [S-1 arm] ) for the treatment of oral squamous cell carcinoma.. Previously non-treated oral squamous cell carcinoma patients were eligible. Patients received 5-FU 600 mg/m(2)iv, as a 24-hour infusion (day 1 to 5) followed by NDP 80 to 100 mg/m(2) iv (day 1), or S-1 60 to 80 mg/m(2) orally twice a day (day 1 to 14) followed by NDP 80 mg/m(2) iv (day 8) every 28 days for one or two cycles.. In total, 32 patients (18 in the 5-FU arm, 14 in the S-1 arm) were enrolled. Twenty patients were male and 12 were female. Median age was 57 years (range 20 years to 87 years). Thirty-one patients had a performance status (PS) oF 0, and 1 patient had a PS 1. Three patients were stage I, 12 stage III, and 12 were stage IV. The overall response rate was 69% (5-FU arm,72%;S-1 arm,64%). Two patients achieved a complete response, 20 patients a partial response, and 10 patients had no change. Grade 3 leucopenia, grade 3 and 4 thrombocytopenia and liver injury occurred in 6% (one in the 5-FU arm, and one in the S-1 arm), 9% (two in the 5-FU arm, and one in the S-1 arm), and 3% (one in the 5-FU arm), respectively. No other severe toxicities were observed.. Response rate and toxicities were similar in both arms. However, the psychosocial stress on patients in the S-1 arm was reduced compared to that in the 5-FU arm, which required hospitalization for a longer period. The outcome in the present study needs further investigation.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Administration Schedule; Drug Combinations; Fluorouracil; Humans; Infusions, Intravenous; Leukopenia; Male; Middle Aged; Mouth Neoplasms; Nausea; Organoplatinum Compounds; Oxonic Acid; Tegafur; Thrombocytopenia; Vomiting, Anticipatory

We report a case of recurrent gastric cancer with peritoneal dissemination and paraaortic lymph node metastases, successfully treated with weekly administration of paclitaxel. The patient was a 63-year-old man who underwent distal gastrectomy with lymph node dissection for advanced gastric cancer in February 2005. After the operation, adjuvant chemotherapy with S-1 was started and continued. He complained of abdominal distention, anorexia and nausea in April 2006. Therefore, paclitaxel (PTX) was administered at a dose of 60 mg/m(2)/day for 3 weeks followed by a week rest. Clinical symptoms were relieved, and abdominal X-ray findings showing intestinal obstruction disappeared after 2 courses. CT scan revealed metastatic lymph nodes were reduced after 3 courses. Grade 1 peripheral neuropathy and grade 2 leukocytopenia were noted, but no serious adverse reaction appeared. Weekly administration of PTX may be a promising regimen as second-line chemotherapy for S-1-resistant recurrent gastric cancer.

Topics: Antineoplastic Agents, Phytogenic; Chemotherapy, Adjuvant; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Gastrectomy; Humans; Leukopenia; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Paclitaxel; Peripheral Nervous System Diseases; Stomach Neoplasms; Tegafur

As a measure to ensure safe use of TS-1 during the early marketing period, a drug use investigation was conducted on an all-case basis. Extra safety monitoring,rarely included in the use investigation,was also planned for patients who began therapy with this agent. Of the 4,177 subjects registered during the year beginning in March 1999, 3,882 started TS-1 therapy. Aside from 74 dropouts, 3,808 cases were evaluable for safety. The overall incidence of adverse reactions, with high frequencies of myelosuppression and gastrointestinal disorders, was 74.3%: a result similar to an incidence of 77.5% (100/129) found in the early phase II trial with gastric cancer patients. Safety monitoring made it possible to check if a given patients was eligible for proper use before treatment is begun. During TS-1 administration,collaboration was formed between physicians and medical representatives to ensure regular laboratory testing and to check the test findings. Measures were considered necessary to secure the safe use of drugs with manifest risk of serious adverse reactions, such as antineoplastic agents, during the initial period of market introduction. Our present approach proved effective as one of such measures.

Topics: Antimetabolites, Antineoplastic; Capsules; Drug Administration Schedule; Drug Combinations; Drug Monitoring; Humans; Leukopenia; Neutropenia; Oxonic Acid; Product Surveillance, Postmarketing; Pyridines; Registries; Stomach Neoplasms; Tegafur; Thrombocytopenia

The aim of this survey was to confirm the safety and efficacy of S-1 for advanced gastric cancer after market release.. All patients had to be registered with the manufacturer for a post-marketing survey, according to the government recommendation. All patients were monitored for safety and survival.. During this survey, a total of 4,177 patients with advanced gastric cancer were registered. The incidences of all adverse events and of grade 3 or worse events in the 3,808 patients evaluable for safety were 74% and 25%, respectively. In patients with lower creatinine clearance at baseline, the incidences of adverse reactions were higher for all grades combined, as well as for grade 3 or worse. There were 90 (2.4%) early deaths (within 30 days of the initiation of the treatment) and 5 (0.1%) deaths possibly related to the treatment. The median survival time and the 1-year survival rate for all patients evaluable for efficacy (n=3,801) were 8.3 months (95% CI: 8.0-8.6 months) and 33.3% (95% CI: 31.8-34.9%), respectively.. This nationwide survey confirmed that the safety and efficacy profiles of S-1 were similar to those seen in the registration study.

Topics: Aged; Anorexia; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Drug Monitoring; Female; Humans; Japan; Leukopenia; Male; Middle Aged; Neutropenia; Oxonic Acid; Product Surveillance, Postmarketing; Registries; Stomach Neoplasms; Survival Rate; Tegafur

The clinical efficacy and safety of weekly paclitaxel therapy were studied retrospectively in 17 patients with advanced and recurrent gastric cancer who had previously been treated with TS-1 therapy. The overall response rate was 0%, but MST was 495 days. The adverse effects observed were grade 3 leukopenia in 2 patients (11.8%) and grade 1 and 2 alopecia in 13 patients (76.5%). However, weekly paclitaxel therapy was performed for all outpatients. Weekly paclitaxel therapy could be useful and safe as second-line chemotherapy.

Topics: Aged; Alopecia; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Paclitaxel; Quality of Life; Stomach Neoplasms; Survival Rate; Tegafur

A 77-year-old man diagnosed with advanced gastric cancer underwent total gastrectomy with combined splenectomy and resection of the pancreatic tails in 1996. He was treated with 400 mg/day of UFT for 2 years. Serum CEA level was found to be elevated on July 5, 2001. He complained of left chest pain in December 2001. A 4 cm-sized tumor was detected in the region extending from the subcutaneous region to the left chest wall containing the osteolytic change of the left sixth rib. He was diagnosed with a chest wall metastasis from gastric cancer. He underwent radiotherapy with thermotherapy and was also treated with chemotherapy. TS-1 was administered at 80-100 mg/body/day, twice daily for 3 weeks followed by a 2-week rest interval as 1 cycle. As a results, shrinkage of the tumor was confirmed on February 14, 2002. The tumor was confirmed to have disappeared on April 17, 2002, by chest CT. A complete response of the metastatic tumor was achieved. The patient maintained a complete response for more than 12 months, but died from the chest wall metastasis recurrence and weakness on August 13, 2003. The only observed adverse event, was grade 2 leukopenia.

Topics: Adenocarcinoma; Administration, Oral; Aged; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Hyperthermia, Induced; Leukopenia; Male; Oxonic Acid; Pyridines; Splenectomy; Stomach Neoplasms; Tegafur; Thoracic Neoplasms

The purpose of this study was to assess the safety of TS-1 when used as adjuvant chemotherapy after surgical resection of advanced stomach cancer.. The subjects were 20 patients with stage III or IV, curability B resected gastric cancer.. The methods consisted of analysis of background factors, assessment of the administration and dosage of TS-1, and associations with adverse reactions.. Mean age was 62.8 years, and the histological type was differentiated in 7 cases and undifferentiated in 13 cases. There were 4 stage IIIA cases, 10 stage IIIB cases, and 6 stage IV cases, and the extent of gastric resection consisted of gastrectomy in 8 cases and total gastrectomy in 12 cases. TS-1 administration was started an average of 57 days postoperatively. The dosage regimen was 4 weeks on and 2 weeks off in 10 cases, and different regimens were used in the other 10 cases. The dose of TS-1 was the recommended dose in 9 cases and a reduced dose in 11 cases, and the mean number of courses was 2.8. Adverse reactions occurred in a total of 14 cases. Digestive system toxicity developed in 5 cases and hematological toxicity in 12. No grade 3 or 4 toxicity was observed. Treatment could be continued in 18 cases. The occurrence of adverse reactions tended to be concentrated immediately after administration of TS-1.. TS-1 was safely used as adjuvant chemotherapy after resection of advanced stomach cancer.

Topics: Aged; Antimetabolites, Antineoplastic; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Gastrectomy; Humans; Leukopenia; Male; Middle Aged; Oxonic Acid; Postoperative Period; Pyridines; Stomach Neoplasms; Tegafur

Chemotherapy with TS-1 has recently become the first-line chemotherapy for recurrent and unresectable gastric cancer in Japan. Therefore, the establishment of a second-line chemotherapy is needed for cases that show resistance and aberrant effect to TS-1. In this study, 7 patients were treated with weekly administrations of paclitaxel after TS-1 treatment. We assessed the therapeutic effect and feasibility of chemotherapy with weekly administration of paclitaxel. Our results showed that weekly administration of paclitaxel could be a promising regimen as a second-line chemotherapy after TS-1.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Edema; Feasibility Studies; Female; Humans; Infusions, Intravenous; Leukopenia; Liver Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Paclitaxel; Pyridines; Stomach Neoplasms; Tegafur

We report a case of advanced squamous cell carcinoma in the left buccal mucosa, upper gingiva, and maxillary sinus (T4N0M0) showing a complete response to oral chemotherapy with TS-1. The patient was an 89-year-old female with severe dementia. We carried out chemotherapy with TS-1 50 mg/day, without surgical treatment. The tumor disappeared clinically at 4 months after 3 courses of the TS-1 administration. Adverse drug reactions, including vomiting, leukopenia and thrombopenia, forced a stop of the administration of TS-1. Although she finally died of in senescence 2 months from the cease of administration, there was no recurrence of the cancer at the time.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Combinations; Female; Gingival Neoplasms; Humans; Leukopenia; Maxillary Sinus Neoplasms; Mouth Mucosa; Mouth Neoplasms; Neoplasm Invasiveness; Oxonic Acid; Pyridines; Remission Induction; Tegafur; Thrombocytopenia; Vomiting, Anticipatory

A total of 40 patients with advanced and recurrent gastric cancer in our hospital were treated with TS-1 alone, and the efficacy of treatment, survival time, and adverse effects were examined. TS-1 was administered with the usual dosage and dose regimen. Response to treatment included a complete response (CR) in 3 cases, partial response (PR) in 8 cases, no change (NC) in 10 cases, and progressive disease (PD) in 7 cases. The response rate was 39.3%, and among the 28 patients with evaluable lesions TS-1 produced a high response rate of 56.3% in 16 patients who had undergone prior therapy. The median survival time (MST) was 478 days in the 28 patients with evaluable lesions, excluding patients with peritoneal dissemination, and 283 days in the 12 patients with peritoneal dissemination. The outcome was markedly poorer in the patients with peritoneal dissemination than in the patients with evaluable lesions. The incidence of grade 3 or higher adverse effects was 20%, including two cases in which decreased dihydropyrimidine dehydrogenase (DPD) activity was suspected, and one case in which decreased dihydropyrimidinase (DHP) was suspected. Although the effect of TS-1 alone on gastric cancer is significantly superior to that of any conventional cancer drugs, the results of this study suggest that the antitumor effect varies with the site of the target lesions and according to whether the lesion is a remnant or recurrence.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Pyridines; Stomach Neoplasms; Survival Rate; Tegafur

Five patients with inoperable advanced gastric cancer were treated with combination chemotherapy of TS-1 and cisplatin (CDDP). TS-1 of 80-120 mg/body/day was orally administered for 3 weeks followed by 2 drug-free weeks, and 60 mg/m2/day of CDDP was venally administered on Day 8. It was possible to evaluate all 5 patients for response and toxicity. Only low grade toxicities (Grade 1 or 2) of leukocytopenia, neutrocytopenia, anemia, nausea, diarrhea and stomatitis were seen. Four of 5 patients achieved a partial response, for a response rate of 80.0%. Stomach, liver, lymph node and peritoneal tumors responded to TS-1/CDDP. TS-1/CDDP therapy produces a high response in cases of gastric cancer, and it is useful as a neoadjuvant chemotherapy.

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Lymphatic Metastasis; Male; Middle Aged; Nausea; Neoadjuvant Therapy; Oxonic Acid; Preoperative Care; Pyridines; Stomach Neoplasms; Tegafur

To examine the adverse reactions to TS-1 for patients with recurrent head and neck cancer, five patients with locoregional recurrences and two with distant metastasis were enrolled in the present study and took TS-1 as outpatients. All patients underwent irradiation with or without surgery before administration of TS-1. One patient was given 100 mg of TS-1 daily, and six patients were given 120 mg of TS-1 daily. Thirteen courses consisted of the regimen of four weeks of TS-1 administration followed by two weeks of intermission, nine courses consisted of the regimen of two weeks of administration followed by one week of intermission, and seven courses consisted of the regimen of two weeks of administration followed by two weeks of intermission. Anemia, leukopenia, neutropenia, and liver dysfunction were often observed as adverse reactions to TS-1 administration. Grade 3 bilirubinemia was observed in only one course, but other adverse reactions consisted of grade 1 or grade 2. Almost all adverse reactions returned to normal after the cessation of drug administration. Based on these results, we conclude that TS-1 is a safe drug for the treatment of outpatients with recurrent head and neck cancer.

Topics: Adult; Aged; Ambulatory Care; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Head and Neck Neoplasms; Humans; Leukopenia; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Pyridines; Tegafur