***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Irinotecan hydrochloride and S-1 , an oral fluoropyrimidine , have shown antitumor activity against advanced gastric cancer as single agents in phase I/II studies . The combination of irinotecan and S-1 ( IRI-S ) is also active against advanced gastric cancer . This study was conducted to compare the efficacy and safety of IRI-S versus S-1 monotherapy in patients with advanced or recurrent gastric cancer . Methods Patients were r and omly assigned to oral S-1 ( 80 mg/m2 daily for 28 days every 6 weeks ) or oral S-1 ( 80 mg/m2 daily for 21 days every 5 weeks ) plus irinotecan ( 80 mg/m2 by intravenous infusion on days 1 and 15 every 5 weeks ) ( IRI-S ) . The primary endpoint was overall survival . Secondary endpoints included the time to treatment failure , 1- and 2-year survival rates , response rate , and safety . Results The median survival time with IRI-S versus S-1 monotherapy was 12.8 versus 10.5 months ( P = 0.233 ) , time to treatment failure was 4.5 versus 3.6 months ( P = 0.157 ) , and the 1-year survival rate was 52.0 versus 44.9 % , respectively . The response rate was significantly higher for IRI-S than for S-1 monotherapy ( 41.5 vs. 26.9 % , P = 0.035 ) . Neutropenia and diarrhea occurred more frequently with IRI-S , but were manageable . Patients treated with IRI-S received more courses of therapy at a relative dose intensity similar to that of S-1 monotherapy . Conclusions Although IRI-S achieved longer median survival than S-1 monotherapy and was well tolerated , it did not show significant superiority in this study Background : A combination of S-1 and cisplatin has been shown to be effective with acceptable safety for the first-line treatment of far-advanced gastric cancer in Japan . This is the first r and omised phase II trial to compare S-1+paclitaxel with S-1+cisplatin in this setting . Methods : Patients with unresectable and /or recurrent advanced gastric cancer were r and omly assigned to receive one of the two regimens : S-1 ( 40 mg m−2 twice daily ) on days 1–14 plus paclitaxel ( 60 mg m−2 ) on days 1 , 8 , and 15 of a 4-week cycle ( S-1+paclitaxel ) or S-1 ( 40 mg m−2 twice daily ) on days 1–21 plus cisplatin ( 60 mg m−2 ) on day 8 of a 5-week cycle ( S-1+cisplatin ) . The primary end point was the response rate ( RR ) . Secondary end points included progression-free survival ( PFS ) , overall survival ( OS ) , and safety . Results : A total of 83 patients were eligible for safety and efficacy analyses . In the S-1+paclitaxel and S-1+cisplatin groups , RRs ( 52.3 % vs 48.7 % ; P=0.74 ) and median PFS ( 9 vs 6 months ; P=0.50 ) were similar . The median OS was similar in the S-1+paclitaxel and S-1+cisplatin groups ( 16 vs 17 months ; P=0.84 ) . The incidence of grade 3 or higher haematological toxicity was 19.0 % with S-1+paclitaxel and 19.5 % with S-1+cisplatin . The incidence of grade 3 or higher non-haematological toxicity was 14.2 % with S-1+paclitaxel and 17.1 % with S-1+cisplatin . Conclusion : S-1+paclitaxel was suggested to be a feasible and effective non-platinum-based regimen for chemotherapy in patients with advanced gastric cancer . Our results should be confirmed in multicenter , phase III-controlled clinical trials Background / Aims : To investigate the efficacy and safety of the combination therapy of irinotecan ( CPT-11 ) plus S-1 in patients with advanced gastric cancer at the dose recommended by a previous phase I study . Methods : A total of 23 patients received 80 mg/m2 of CPT-11 on days 1 and 15 , and S-1 at a dose level set on the basis of the body surface area ( BSA ) : 40 ( BSA < 1.25 m2 ) , 50 ( BSA ≧1.25 to < 1.5 m2 ) or 60 mg ( BSA ≧1.5 m2 ) b.i.d . was given from days 1–21 . Results : The overall response rate was 47.8 % ( 11 of 23 , 95 % confidence interval , CI : 27.4–68.2 % ) . The median time to progression ( TTP ) was 210 days ( 95 % CI : 145–322 days ) and the median survival time was 394 days ( 95 % CI : 241–484 days ) . The incidence of grade 3 or 4 hematological and non-hematological toxicity was 17.4 and 8.7 % . The most common hematological toxicity was anemia and the most common non-hematological toxicity was diarrhea . Conclusion : The combination therapy of CPT-11 and S-1  provided prolonged TTP with low toxicity , and the results warrant a further phase III study to define the efficacy in improvement of survival in patients with advanced gastric cancer BACKGROUND The efficacy and safety of oxaliplatin combined with S-1 ( SOX regimen ) for unresectable advanced or recurrent gastric cancer were investigated . PATIENTS AND METHODS Oxaliplatin was administered i.v . ( 100 mg/m(2 ) ) on day 1 , while S-1 was administered orally ( 80 mg/m(2)/day , b.i.d . ) for 14 days followed by a 7-day rest . This schedule was repeated every 3 weeks . RESULTS Among 55 patients enrolled , one patient received oxaliplatin for the other study , and three patients were considered unsuitable against the inclusion criteria . Accordingly , 51 patients were assessable for efficacy . The response rate was 59 % , and the disease control rate was 84 % . The median progression-free survival time was 6.5 months , the 1-year survival rate was 71 % , and the median survival time was 16.5 months . In 54 patients assessed for safety , the major grade 3/4 toxic effects were neutropenia ( 22 % ) , thrombocytopenia ( 13 % ) , anemia ( 9 % ) , anorexia ( 6 % ) , fatigue ( 6 % ) , and sensory neuropathy ( 4 % ) . CONCLUSION These findings indicate that SOX regimen with oxaliplatin at a dose of 100 mg/m(2 ) is feasible and shows promising efficacy against advanced gastric cancer Purpose To evaluate the comprehensive safety profile of S-1 , a promising novel oral fluoropyrimidine derivative , based on large cohort data . Patients and methods Study subjects were identified from a prospect i ve registry of 3,758 advanced gastric cancer patients in Japan . Each patient was treated with an identical regimen of S-1 monotherapy ( 40 mg b.i.d . on days 1–28 , every 6 weeks ) and assessed for all adverse events . Results The median duration of treatment was 88 days ; 1,605 ( 43 % ) patients underwent three or more treatment cycles . The relative dose intensity was 0.87 in the first two cycles ( short-term treatment period ) and 0.89 thereafter ( long-term treatment period ) . Neutropenia was the most common severe ( grade 3–4 ) hematological event ( 6.3 % in the short-term period and 5.3 % in the long-term period ) . Other hematological or key gastrointestinal events ( diarrhea , nausea/vomiting , and stomatitis ) had a low incidence of severe cases throughout the whole administration period ( 0.3–3.8 % ) . The time to onset of severe events did not differ between patients with mild renal impairment ( creatinine clearance , 50–79 ml/min ) and those with normal renal function ( ≥80 ml/min ) ( hazard ratio , 1.04 ; 95 % CI , 0.87–1.23 ; P = 0.691 ) . Conclusions S-1 had manageable severe toxicity and allowed good compliance regardless of treatment duration . Prolonged administration of the drug was sustainable Abstract Purpose Cisplatin plus 5-fluorouracil has been globally accepted as a st and ard regimen for the treatment for advanced gastric cancer . However , cisplatin has several disadvantages , including renal toxicity and the need for admission . S-1 plus cisplatin has become a st and ard treatment for advanced gastric cancer in East Asia . This phase III study was design ed to evaluate the potential benefits of adding docetaxel to S-1 without a platinum compound in patients with advanced gastric cancer . Methods Patients were r and omly assigned to receive docetaxel plus S-1 or S-1 alone . The docetaxel plus S-1 group received docetaxel on day 1 and oral S-1 on days 1–14 of a 21-day cycle . The S-1 alone group received oral S-1 on days 1–28 of a 42-day cycle . The primary end point was overall survival . Results Of the 639 patients enrolled , 635 were eligible for analysis .  The median overall survival was 12.5 months in the docetaxel plus S-1 group and 10.8 months in the S-1 alone group ( p = 0.032 ) . The median progression-free survival was 5.3 months in the docetaxel plus S-1 group and 4.2 months in the S-1 alone group ( p = 0.001 ) . As for adverse events , neutropenia was more frequent in the docetaxel plus S-1 group , but remained manageable . Conclusion As first-line treatment for advanced gastric cancer , docetaxel plus S-1 significantly improves median overall and progression-free survival as compared with S-1 alone . ( Clinical Trials.gov number : NCT00287768 ) Purpose This r and omized phase II study was conducted to compare the efficacy and safety of paclitaxel with S-1 ( PS ) vs. S-1 in patients with advanced gastric cancer ( AGC ) . Methods Eighty-two ( 82 ) patients were 1:1 r and omly assigned to oral S-1 ( daily for 2 weeks , every 4 weeks ’ cycle ) or S-1 ( daily for 2 weeks , every 4 weeks ’ cycle ) plus paclitaxel ( on day 1 , 8 and 15 of a 4 weeks ’ cycle ) . S-1 was orally administered with a fixed quantity according to body surface area ( BSA ) , while paclitaxel was given 60 mg/m2 i.v . daily through an implanted catheter . The primary endpoint was overall survival ( OS ) . Secondary endpoints included progression-free survival ( PFS ) , overall responsible rates and safety . Results The median OS with PS versus S-1 monotherapy was 14.0 versus 11.0 months ( P = 0.02 ) , survival at 12 months was 61.0 % in the PS group and 46.3 % in the S-1 group . Median PFS was also significantly longer in the PS group ( 6.0 months ) than in the S-1 group ( 4.0 months ) . The overall response rate was determined in 82 evaluable patients , and was significantly higher ( P = 0.04 ) with PS ( 19 patients , 46.3 % ) than with S-1 monotherapy ( 10 patients , 24.4 % ) . PS was well tolerated with no treatment-related deaths , all were grade 3–4 gastrointestinal toxicities , including anorexia , nausea , and diarrhea developed in less than 10 % of the patients . Conclusions Combination chemotherapy of paclitaxel with S-1 is well tolerated and active in AGC patients . Further investigation with comparative trials is needed for confirmation BACKGROUND The aim of developing oral fluorouracil ( 5-FU ) is to provide a more convenient administration route with similar efficacy and the best achievable tolerance . S-1 , a novel oral fluoropyrimidine , was specifically design ed to overcome the limitations of intravenous fluoropyrimidine therapies . PATIENTS AND METHODS A multicentre , r and omised phase 3 trial was undertaken to compare S-1/cisplatin ( CS ) with infusional 5-FU/cisplatin ( CF ) in 1053 patients with untreated , advanced gastric/gastroesophageal adenocarcinoma . This report discusses a post-hoc noninferiority overall survival ( OS ) and safety analyses . RESULTS Results ( 1029 treated ; CS = 521/CF = 508 ) revealed OS in CS ( 8.6 months ) was statistically noninferior to CF ( 7.9 months ) [ hazard ratio ( HR ) = 0.92 ( two-sided 95 % confidence interval ( CI ) , 0.80 - 1.05 ) ] for any margin equal to or greater than 1.05 . Statistically significant safety advantages 
    Output:
    
Lower incidence of grade 1–4 nausea , diarrhea , mucositis , grade 3–4 mucositis , increased creatinine , and decreased calculated creatinine clearance was observed in S-1-containing regimens .
S-1 could not improve OS , but increase some hematological toxicities in Asian patients .