s-1-(combination) and Thrombocytopenia

The combination with cisplatin (CDDP) and 5-FU is considered the first choice chemotherapy for squamous cell carcinoma of the head and neck (HNSCC). S-1, a modulation of tegafur developed in Japan, is an active agent for HNSCC. Some clinical phase I/II studies about the combination with CDDP and S-1 have been reported. The combination showed a good response rate of 67.6% for advanced and recurrent HNSCC in our clinical phase I/II study. The regimens of S-1 combined with carboplatin or nedaplatin have also been reported. Regimens containing S-1 appear to have been effective for HNSCC. Multi-institutional phase II studies with a large sample size are needed in the future. The compliance for patients is better than a 5-FU injection because S-1 is orally administrated. The adverse effect, especially for bone mallow toxicity, is equal or upgraded compared with a 5-FU injection. The efficacy and adverse effects of CDDP plus S-1 should be studied in carefully designed phase II/III trials. S-1 will be one of the key drugs for HNSCC in the future.

Topics: Adult; Aged; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Carcinoma, Squamous Cell; Cisplatin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Administration Schedule; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Tegafur; Thrombocytopenia

Combination carboplatin and S-1 is active in the treatment of non-small cell lung cancer (NSCLC). However, data on this combination for elderly patients with NSCLC are insufficient.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Carboplatin; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Neutropenia; Oxonic Acid; Survival Rate; Tegafur; Thrombocytopenia; Treatment Outcome

Previous studies have shown sex-related differences in the incidence of adverse events following treatment with fluoropyrimidines, however the mechanism of this difference is unknown. We examined sex-related differences in the safety of S-1 plus oxaliplatin (SOX) and S-1 plus cisplatin (CS) in 663 metastatic gastric cancer patients taking part in a phase III study. The incidences of leukopenia (odds ratio [OR] 1.9; P = .015), neutropenia (OR 2.2; P = .002), nausea (OR 2.0; P = .009), and vomiting (OR 2.8; P < .001) were increased in women versus men treated with SOX, while vomiting (OR 2.9; P < .001) and stomatitis (OR 1.8; P = .043) were increased in women versus men treated with CS. In contrast, male patients treated with CS experienced thrombocytopenia more often (OR 0.51; P = .009). The mean relative dose intensity of S-1 in SOX was 75.4% in women and 81.4% in men (P = .032). No difference in efficacy was observed between women and men undergoing either regimen. Sex-related differences in adverse reactions during SOX and CS treatment were confirmed in this phase III study. Further translational research studies are warranted to pursue the cause of this difference.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Incidence; Male; Middle Aged; Nausea; Neutropenia; Oxaliplatin; Oxonic Acid; Sex Factors; Stomach Neoplasms; Stomatitis; Tegafur; Thrombocytopenia; Vomiting

A phase II study was performed to investigate the safety and efficacy of concurrent chemoradiotherapy (CCRT) combined with an orally active fluoropyrimidine, S-1, plus cisplatin for locally advanced esophageal cancer (LAEC).. CCRT comprised 2 courses, a 30-Gy radiotherapy over 3 weeks plus daily oral S-1 (80 mg/m(2)/day) for 2 weeks and a 24-hour cisplatin infusion (70 mg/m(2)) on day 8, and an identical course administered after a 2-week break.. One hundred and sixteen patients, 12 with stage II, 71 with stage III, and 33 with stage IVa LAEC participated, and 106 of them (91.4%) completed the CCRT course. The most serious toxicity was myelosuppression: grade 3 and 4 neutropenia occurred in 28.4 and 9.5% of patients, respectively. Nonhematologic toxicity was moderate. Complete response rates in patients with stage II, III, and IVa LAEC were 91.7, 67.6, and 36.4%, respectively. The overall median survival time was 2.3 years and that of patients with stage II, III, and IVa cancer was 7.0, 2.6, and 1.3 years, respectively.. CCRT combined with S-1 plus cisplatin showed promising safety and efficacy. Potentially, this combination therapy could become a baseline medication for patients with LAEC.

Topics: Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Cisplatin; Disease Progression; Drug Combinations; Esophageal Neoplasms; Female; Humans; Kaplan-Meier Estimate; Male; Medication Adherence; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Radiotherapy Dosage; Survival Rate; Tegafur; Thrombocytopenia; Time Factors; Treatment Failure

The purpose of this study was to evaluate the feasibility and compliance of adjuvant chemotherapy of S-1 plus carboplatin for patients with completely resected non-small cell lung cancer (NSCLC) of pathological stage IB-IIIB.. S-1 was given orally at a dose of 80 mg/m²/day for 2 weeks, followed by a 2-week period of no treatment. Carboplatin was given intravenously on day 8 at an area under the curve of 6. This regimen was repeated for four to six 28-day courses.. Seventeen patients were enrolled in this study. Fourteen of them completed at least 4 cycles of chemotherapy. Nine patients had grade 2 and three patients had grade 3 thrombocytopenia, respectively. Severe nonhematologic toxicities were uncommon. Treatment was delayed in a few patients because of prolonged thrombocytopenia.. We concluded that the regimen was feasible and tolerable for patients with completely resected NSCLC as adjuvant chemotherapy.

Topics: Aged; Antineoplastic Agents; Area Under Curve; Carboplatin; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; ROC Curve; Tegafur; Thrombocytopenia; Treatment Outcome

We previously reported on the regimen of S-1 plus nedaplatin (NDP), with S-1 was administered orally for 14 days and NDP intravenously on day 8. The maximum tolerated dose (MTD) of NDP was determined to be 90 mg/m². The main toxicities were neutropenia and thrombocytopenia. This result was tolerated, but we believe there is a more effective and tolerable regimen. Thus, we investigated the S-1 regimen administered orally for 14 days, and NDP intravenously on day 1 in patients with locally advanced head and neck squamous cell carcinoma.. Oral administration of S-1 (days 1-14) and intravenous NDP (day 1) were tested for patients with advance head and neck cancer in a phase I setting. The dose of S-1 was fixed and the dose of NDP was escalated from 70 mg/m², with an increase of 10 mg/m² per step, to find the MTD.. A total of 15 patients were registered. The MTD of NDP was determined to be 100 mg/m². The main toxicities were neutropenia and thrombocytopenia. The response rate (RR) was 57.1%.. The recommended dose of NDP for a phase II study was determined to be 100 mg/m². We concluded that our regimen was well tolerated and that the RR was acceptable.

Topics: Administration, Oral; Aged; Antineoplastic Agents; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Head and Neck Neoplasms; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neutropenia; Organoplatinum Compounds; Oxonic Acid; Tegafur; Thrombocytopenia; Treatment Outcome

We evaluated the efficacy and safety of a combination of S-1 and cisplatin (SP) versus gemcitabine and cisplatin (GP) as first-line therapy for advanced biliary tract adenocarcinoma (ABTA).. Patients were randomized to receive cisplatin (60 mg/m(2) intravenously [IV] on Day 1) plus S-1 (40 mg/m(2) bid orally on Days 1-14) or gemcitabine (1000 mg/m(2) IV at 10 mg/m(2)/min on Days 1 and 8) every three weeks. The primary end point was six-month progression-free survival (PFS).. Of 96 eligible patients, 49 were randomized to GP and 47 to SP. At a median follow-up time of 14.2 months, the six-month PFS rates were 43.8% and 34.7%, respectively [unadjusted HR (GP/SP) =0.85, 95% CI 0.52-1.36]. The median OS values in the GP and SP groups were 10.1 months and 9.9 months, respectively [unadjusted HR (GP/SP) =0.72, 95% CI 0.45-1.17]. Grade 3-4 toxicities in the GP and SP groups included neutropenia (49.0% vs. 31.8%), anemia (22.4% vs. 2.3%), thrombocytopenia (22.4% vs. 4.5%), and asthenia (4.1% vs. 2.1%).. Both GP and SP has comparable efficacy with favorable safety profile as first-line treatment for ABTA. (ClinicalTrials.gov number NCT 01375972).

Topics: Adenocarcinoma; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Asthenia; Biliary Tract Neoplasms; Cisplatin; Deoxycytidine; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Follow-Up Studies; Gemcitabine; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Male; Middle Aged; Neutropenia; Oxonic Acid; Severity of Illness Index; Tegafur; Thrombocytopenia; Treatment Outcome

To perform a Phase I study of preoperative chemoradiation (CRT) with S-1, a novel oral fluoropyrimidine, plus oxaliplatin in patients with locally advanced rectal cancer, to determine the maximum tolerated dose and the recommended dose.. Radiotherapy was delivered to a total of 45 Gy in 25 fractions and followed by a coned-down boost of 5.4 Gy in 3 fractions. Concurrent chemotherapy consisted of a fixed dose of oxaliplatin (50 mg/m2/week) on Days 1, 8, 22, and 29 and escalated doses of S-1 on Days 1-14 and 22-35. The initial dose of S-1 was 50 mg/m2/day, gradually increasing to 60, 70, and 80 mg/m2/day. Surgery was performed within 6±2 weeks.. Twelve patients were enrolled and tolerated up to Dose Level 4 (3 patients at each dose level) without dose-limiting toxicity. An additional 3 patients were enrolled at Dose Level 4, with 1 experiencing a dose-limiting toxicity of Grade 3 diarrhea. Although maximum tolerated dose was not attained, Dose Level 4 (S-1 80 mg/m2/day) was chosen as the recommended dose for further Phase II studies. No Grade 4 toxicity was observed, and Grade 3 toxicities of leukopenia and diarrhea occurred in the same patient (1 of 15, 6.7%). Pathologic complete responses were observed in 2 of 15 patients (13.3%).. The recommended dose of S-1 was determined to be 80 mg/m2/day when combined with oxaliplatin in preoperative CRT, and a Phase II trial is now ongoing.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Nausea; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Preoperative Care; Radiotherapy Dosage; Rectal Neoplasms; Tegafur; Thrombocytopenia; Vomiting

To carry out a phase II multi-center study on the efficacy and safety of triple combination therapy with paclitaxel, S-1, and cisplatin in patients with unresectable/metastatic gastric cancer.. A total of 63 patients from 8 institutions were included in this study. Paclitaxel (160 mg/m²) was administered by infusion for 3 h on the first day. S-1 (70 mg/m²/day) was administered orally for 14 consecutive days from the first day. Cisplatin (60 mg/m²) was administered intravenously over 24 h on day 14 of every 28-day cycle.. All 63 patients were assessed for clinical efficacy and safety. A total of 259 cycles of treatment were administered (median 4, range 1-10). Grade 3-4 toxicities included neutropenia in 30.2%, thrombocytopenia in 12.7%, and anemia in 11.1%. There was no grade 3-4 non-hematological toxicity or treatment-related death. Complete response was observed in 6 patients and partial response in 34 patients. The overall response rate was 63.5%. The median progression-free survival and response duration were 8.0 and 8.8 months, respectively, and median survival time was 15 months.. Triple combination therapy with paclitaxel, S-1, and cisplatin showed promising safety and efficacy profiles with the potential to become a standard regimen for unresectable/metastatic gastric cancer.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neutropenia; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Survival Rate; Tegafur; Thrombocytopenia; 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

To evaluate the combination chemotherapy using oral antimetabolite S-1 plus cisplatin (SP) with concurrent thoracic radiotherapy (RT) followed by the consolidation SP for locally advanced non-small cell lung cancer.. Patients with stage III non-small cell lung cancer, 20 to 74 years of age, and Eastern Cooperative Oncology Group performance status 0 to 1 were eligible. The concurrent phase consisted of full dose S-1 (orally at 40 mg/m/dose twice daily, on days 1-14) and cisplatin (60 mg/m on day 1) repeated every 4 weeks for two cycles with RT delivered beginning on day 1 (60 Gy/30 fractions over 6 weeks). After SP-RT, patients received an additional two cycles of SP as the consolidation phase.. Fifty-five patients were registered between November 2006 and December 2007. Of the 50 patients for efficacy analysis, the median age was 64 years; male/female 40/10; Eastern Cooperative Oncology Group performance status 0/1, 21/29; clinical stage IIIA/IIIB 18/32; and adenocarcinoma/others 20/30. There were 42 clinical responses including one complete response with an objective response rate of 84% (95% confidence interval [CI], 71-93%). The 1- and 2-year overall survival rates were 88% (95% CI, 75-94%) and 70% (95% CI, 55-81%), respectively. The median progression-free survival was 20 months. Of the 54 patients for safety analysis, common toxicities in the concurrent phase included grade 3/4 neutropenia (26%), thrombocytopenia (9%), and grade 3 esophagitis (9%) and febrile neutropenia (9%). In one patient, grade 3 pneumonitis was observed in the consolidation phase. There were two treatment-related deaths caused by infection in the concurrent phase.. SP-RT showed a promising efficacy against locally advanced NCSLC with acceptable toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Disease-Free Survival; Dose Fractionation, Radiation; Drug Combinations; Esophagitis; Female; Fever; Humans; Japan; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; 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

We conducted a phase II study of S-1 and carboplatin combination regimen in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Chemotherapy-naïve patients with advanced NSCLC were treated with S-1 and carboplatin. S-1 was administered orally twice daily for 14 days and carboplatin AUC 5 on day 1 of each cycle, and this was repeated every 4 weeks. Twenty-nine patients were enrolled in this study. The main grade 3 or 4 toxicities observed during the first cycle were neutropenia (10.3%), thrombocytopenia (41%), and transaminase elevation. Objective responses were seen in 9 patients (response rate 31.0%). The median survival time and median progression-free survival were 16.0 months (95% CI, 12.1-19.0 months) and 4.5 months (95% CI, 3.2-6.1 months), respectively. Hematological adverse events reaching grade 3 or 4 were neutropenia (10.3%), anemia (3.4%), and thrombocytopenia (3.4%). No febrile neutropenia was detected. Nonhematological toxicities were also mild. Although grade 3 infection was observed in 1 patient, the patient improved without intervention. The combination of S-1 plus carboplatin is an active and well-tolerated regimen for the treatment of patients with advanced NSCLC. Further investigations are required to confirm our results in randomized trials.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Tegafur; Thrombocytopenia

Optimal chemotherapy for advanced biliary tract cancer (BTC) is yet to be defined. We carried out this study to evaluate the efficacy and toxicity of combination chemotherapy with S-1 and cisplatin in metastatic or relapsed BTC.. Patients with pathologically proven BTC were eligible. The chemotherapy regimen consisted of S-1 (40 mg/m(2) p.o. b.i.d. from D1-14) and cisplatin (60 mg/m(2) on D1), repeated every 3 weeks.. Fifty-one BTC patients (metastatic:relapsed = 37:14, Gall-bladder:intrahepatic bile ducts:extrahepatic bile ducts = 16:25:10) were enrolled from January 2005 to December 2006. Median age was 57 years (range, 31-71) and most patients had a good performance status. The overall response rate was 30% [95% confidence interval (CI), 17.3-42.7] and complete response was observed in two patients (4%), partial response in 13 (26%), stable disease in 21 (42%), and progressive disease in 9 (18%). With a median follow-up of 12.4 months, the median time to progression was 4.8 months (95% CI, 3.3-6.3) and median overall survival was 8.7 months (95% CI, 6.0-11.4). Major toxic effects were grade 3/4 neutropenia (8.9% of all cycles) and febrile neutropenia was observed in six cycles (2.7% of all cycles).. Combination chemotherapy with S-1 and cisplatin was a moderately effective outpatient-based regimen in BTC patients. Toxic effects were moderate but manageable.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Cisplatin; Disease Progression; Disease-Free Survival; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neutropenia; Oxonic Acid; Pyridines; Salvage Therapy; Survival Analysis; Tegafur; Thrombocytopenia

A pre-clinical study demonstrated that paclitaxel induced thymidine phosphorylase in the tumor tissues. The combination of paclitaxel and doxifluridine is expected to exert extra anti-tumor effects. We evaluated the efficacy of this combination in patients with unresectable or recurrent gastric cancer who had been previously treated with S-1.. Registration was started to enroll 35 patients with advanced/recurrent gastric cancer, who were selected among those with measurable lesions fitting to response evaluation criteria in solid tumors, and with resistant to S-1 treatment. This regimen is consisted of paclitaxel, 80 mg/m(2), iv on days 1 and 8; and doxifluridine, 600 mg/m(2), po on days 1-14. The treatment was repeated every three weeks. Primary endpoint was response rate (RR); and secondary endpoints were overall survival (OS), progression free survival (PFS) and onset rate of adverse events.. From September 2003 to March 2005, 35 patients were registered: including 28 men; 7 women; median age of 66 years (range, 49-75 years); and performance status (PS) levels were, zero with 21 and one with 14 patients. In 33 eligible patients, except two, clinical usefulness was evaluated resulting in RR of 18.2% (partial response, 6; stable disease, 15; progressive disease, 10; and not evaluable, 2 patients). Median survival time was 321 days and median PFS was 119 days. Severe adverse events were found in three patients to discontinue the present treatment.. The combination of paclitaxel and doxifluridine might be a treatment of choice as a second line chemotherapy for patient undergone S-1 treatment.

Topics: Adenocarcinoma; Aged; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Drug Combinations; Drug Resistance, Neoplasm; Female; Floxuridine; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms; Survival Rate; Tegafur; Thrombocytopenia

The incidence and mortality of pancreatic cancer has increased very rapidly in Japan. The five-year survival rate is still poor at less than 10%, because it is commonly considered to be linked to a high incidence of distant metastasis even at the initial diagnosis as well as to the tumor's resistance to anticancer agents. Although gemcitabine has been the most widely used chemotherapeutic agent in patients with advanced pancreatic cancer (APC), gemcitabine monotherapy has obvious limitations. Therefore, various combinations with other agents have been investigated to improving the survival of patients with APC. Under these circumstances, we conducted a phase I /II trial of gemcitabine with S-1, an oral fluorouracil derivative, to determine the maximum tolerated dose and to evaluate the activity and toxicity of such a combination in patients with APC. S-1 was administered orally twice daily each day for 14 days and gemcitabine on days 8 and 15 of each cycle, and this cycle was repeated every 21 days. As a result, S-1 30 mg/m2 orally twice daily and gemcitabine 1,000 mg/m2 were selected as the recommended dose. The toxicities observed were mainly hematological ones with mild non-hematological toxicities. An encouragingly high response rate was observed. This result is very promising, but the survival benefit in comparison with gemcitabine monotherapy needs to be confirmed in a future randomized clinical trial.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Administration Schedule; Drug Combinations; Gemcitabine; Humans; Maximum Tolerated Dose; Middle Aged; Nausea; Oxonic Acid; Pancreatic Neoplasms; Survival Rate; Tegafur; Thrombocytopenia

Chemoradiotherapy combined with 5-fluorouracil and cisplatin have been effective for the treatment of advanced esophageal cancer, but superior treatments are needed. We prospectively analyzed the efficacy of concurrent chemoradiotherapy using oral fluoropyrimidine (S-1) and cisplatin for the treatment of advanced esophageal cancer.. The treatment protocol was determined on a phase I study. The first chemoradiotherapy course consisted of 30 Gy over 3 weeks, a daily oral administration of S-1 (80 mg/m2/day) for 2 weeks, and a 24-hour infusion of cisplatin (70 mg/M2) on day 8. A second course of chemoradiotherapy was performed after an interval of 2 weeks.. Seventy-one patients entered to this phase II study for five years (stage II: n=6, stage III: n=40, stage IV: n=25). All the stage II patients obtained a complete response, while 55% and 93% of the stage III patients and 20% and 76% of the stage IV patients obtained complete and partial responses, respectively. The major toxicity was myelosuppression. Eight patients (11%)developed a grade 4 leukocytopenia. The median survival times were thirty-nine months and eleven months for the stage II + stage III and stage IV patients, respectively.. Chemoradiotherapy combined with S-1 and cisplatin may be a promising treatment option for advanced esophageal cancer.

Topics: Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prospective Studies; Radiotherapy Dosage; Survival Rate; Tegafur; Thrombocytopenia

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

Three randomised trials (GEST, JACCRO PC-01, and GEMSAP) were conducted to evaluate the efficacy of gemcitabine plus S-1 (GS) vs gemcitabine alone in patients with advanced pancreatic cancer (PC). In this pooled analysis, the efficacy and safety of GS vs gemcitabine were evaluated.. Additional follow-up was conducted and survival data were updated in each study. A total of 770 patients (gemcitabine 389; GS 381) were included in the pooled analysis. The efficacy and safety data were analysed according to disease extent: locally advanced PC (LAPC) or metastatic PC (MPC).. There were 738 (95.8%) overall survival events. In patients with LAPC (n=193), the median survival was 11.83 months for gemcitabine and 16.41 months for GS (hazard ratio (HR)=0.708; 95% confidence intervals (CI), 0.527-0.951; P=0.0220). In patients with MPC (n=577), the median survival was 8.02 months for gemcitabine and 9.43 months for GS (HR=0.872; 95% CI, 0.738-1.032; P=0.1102). The rate of grade 3/4 toxicity (rash and thrombocytopenia in LAPC; rash, diarrhoea, vomiting, and neutropaenia in MPC) was significantly higher for GS than for gemcitabine.. Gemcitabine plus S-1 is a viable treatment alternative to gemcitabine, which is one of the standard treatments in patients with LAPC.

Topics: Aftercare; Aged; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Deoxycytidine; Diarrhea; Drug Combinations; Drug Eruptions; Female; Gemcitabine; Humans; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Oxonic Acid; Pancreatic Neoplasms; Randomized Controlled Trials as Topic; Survival Rate; Tegafur; Thrombocytopenia; Vomiting

Both docetexal plus S-1 (DS) and oxaliplatin plus S-1 (SOX) are active regimens currently used in patients with advanced gastric cancer. In this retrospective study, efficacy and safety of these 2 combination regimens were evaluated.. Patients received docetaxel infusion 75 mg/m(2) in the DS group or oxaliplatin infusion 130 mg/m(2) in the SOX group at day 1 of each 3-week cycle. S-1 40 mg/m(2) was administered orally twice daily on days 1-14 in the 3-week cycle in both groups. Progression-free survival (PFS), overall survival (OS) and safety perimeters were evaluated.. 84 patients were retrospectively evaluated in the study: 36 patients in the DS group and 48 patients in the SOX group. The median PFS was 6.55 months in the DS group and 5.73months in the SOX group. The median OS was 13.97 in the DS group and 13.13 months in the SOX group. The overall response rates were 41.7% and 43.8% and the disease control rates were 77.8% and 87.5% for DS and SOX, respectively. The most frequent grade 3 and 4 toxicities were thrombocytopenia for DS (19.4%) and anemia for SOX (12.5%).. Both regimens were active and well tolerated in advanced gastric cancer patients. © 2014 S. Karger GmbH, Freiburg.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Tegafur; Thrombocytopenia; Treatment Outcome

To evaluate the efficacy and safety of the regimen of low-dose high intensity focused ultra-sound (HIFU) plus S-1 and oxaliplatin (SOX) in the treatment of metastatic colorectal cancer patients with pelvic masses.. A total of 46 patients with metastatic colorectal cancer were recruited and divided into 2 groups: Twenty patients received concurrent HIFU plus S-1 and oxaliplatin (SOX) while another 26 patients SOX alone. The baseline characteristics, progressive-free survival, overall survival time and adverse events were retrospectively analyzed.. The median PFS was 11.2 months (95% CI 9.8-12.7) in the HIFU+SOX group and 7.1 months (95% CI 5.8-8.4) in the SOX group (P = 0.003). And the overall survival time in two groups were 21.9 months (95% CI 18.0-25.9) and 16.9 months (95%CI 14.1-19.6) (P = 0.072) respectively. Major toxic effects included grade 3/4 neutropenia (15%), anemia (10%), thrombocytopenia (10%), diarrhea (15%) and hand-foot syndrome (10%) in the HIFU+SOX group. And it showed no statistically significant differences with the SOX group.. The combined regimen of HIFU and SOX is effective and well-tolerated in patients of late-stage colorectal cancer with pelvic masses.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Combinations; Humans; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Pelvic Neoplasms; Retrospective Studies; Tegafur; Thrombocytopenia; Treatment Outcome; Ultrasonography

The combination of oxaliplatin and S-1 is effective in patients with advanced gastric cancer. The purpose of this study was to analyze the safety and compliance of this combination regimen as adjuvant chemotherapy in patients with gastric cancer.. Clinical data of 71 patients with gastric cancer treated with oxaliplatin plus S-1 as adjuvant chemotherapy in the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) from Jan 1(st), 2010 to Jan 1(st), 2012 were retrospectively reviewed. The types and incidence rate of adverse events related to chemotherapy and the results of follow up of the patients were analyzed.. Among the 71 cases, 17 were treated with oxaliplatin biweekly, while 54 with oxaliplatin triweekly. The most common adverse events were neutropenia (n = 49, 69.0%), nausea/vomiting (n = 51, 71.8%), and anorexia (n = 49, 69.0%). The most frequent grade 3-4 toxicities were neutropenia (n = 13, 18.3%), thrombocytopenia (n = 10, 14.1%), anorexia (n = 5, 7.0%) and nausea/vomiting (n = 4, 5.6%). Seven (87.5%) of the 8 patients previously treated with neoadjuvant chemotherapy experienced thrombocytopenia in the postoperative adjuvant chemotherapy, and four (50%) of the 8 patients experienced grade 3-4 thrombocytopenia. The rates of grade 3-4 adverse events in patients aged 65-years or older were similar to that in younger patients.. The combination of oxaliplatin and S-1 used as adjuvant chemotherapy is well tolerated by patients with gastric cancer. Neutropenia, thrombocytopenia, nausea/vomiting and anorexia are the major treatment-related adverse events. Patients who received neoadjuvant chemotherapy do not well tolerate this regimen as postoperative adjuvant chemotherapy. This combination regimen has a manageable tolerability profile in adjuvant setting in patients ≥ 65 years old.

Topics: Adenocarcinoma; Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nausea; Neoadjuvant Therapy; Neoplasm Staging; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur; Thrombocytopenia

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

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

We report a case of right maxillary carcinoma with metastases to the cervical lymph nodes (T4N2cM0, Stage IV). A 76-year-old woman was administered preoperative chemoradiotherapy, followed by curative surgery. TS-1 (80 mg/day), CDDP (5 mg/m2/day) and concurrent radiation (total 40 Gy) induced a complete response. Grade 2 neutropenia, thrombocytopenia and stomatitis were observed. In the primary tumor and cervical metastatic lymph nodes, no viable carcinoma cells were detected and cancer nests were replaced with marked fibrous tissue.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Maxillary Neoplasms; Neck; Neutropenia; Oxonic Acid; Pyridines; Radiotherapy, Adjuvant; Stomatitis; Tegafur; Thrombocytopenia

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