***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: Purpose To evaluate the efficacy and safety of the combination of gemcitabine ( GEM ) and S-1 ( GS ) in comparison to GEM alone ( G ) for unresectable pancreatic cancer . Methods In this multicenter r and omized phase II study , we r and omly assigned unresectable pancreatic cancer patients to either the GS group or the G group . The GS group regimen consists of intravenous 1,000 mg/m2 GEM during 30 min on days 1 and 8 , combined with 80 mg/m2 oral S-1 twice daily on days 1–14 , repeated every 3 weeks . On the other h and , the G group regimen consists of intravenous 1,000 mg/m2 GEM on days 1 , 8 , and 15 , repeated every 4 weeks . The primary endpoint was objective response rate ( ORR ) . Secondary end points included treatment toxicity , clinical response benefit , progression-free survival ( PFS ) , and overall survival . Results We registered 117 patients from 16 institutions between June 2007 and August , 2010 . The ORR of the GS group was 28.3 % , whereas that of the G group was 6.8 % . This difference was statistically significant ( P = 0.005 ) . The disease control rate was 64.2 % in the GS group and 44.1 % in the G group . Median PFS was 6.15 months in the GS group and 3.78 month in the G group . This was also statistically significant ( P = 0.0007 ) . Moreover , the median overall survival ( OS ) of the GS group was significantly longer than that of the G group ( 13.7 months vs. 8.0 months ; P = 0.035 ) . The major grade 3–4 adverse events were neutropenia ( 54.7 % in the GS group and 22.0 % in the G group ) , thrombocytopenia ( 15.1 % in the GS group and 5.1 % in the G group ) , and skin rash ( 9.4 % in the GS group ) . Conclusions The GS group showed stronger anticancer activity than the G group , suggesting the need for a large r and omized phase III study to confirm GS advantages in a specific subset Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background : This r and omised phase II trial compared gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer . Methods : Patients were r and omly assigned to 4-week treatment with gemcitabine alone ( 1000 , mg m−2 gemcitabine by 30-min infusion on days 1 , 8 , and 15 ) or gemcitabine and S-1 combination therapy ( 1000 , mg m−2 gemcitabine by 30-min infusion on days 1 and 15 and 40 mg m−2 S-1 orally twice daily on days 1–15 ) . The primary end point was progression-free survival ( PFS ) . Results : Between July 2006 and February 2009 , 106 patients were enrolled .  The PFS  in gemcitabine and S-1 combination arm was significantly longer than in gemcitabine arm ( 5.4 vs 3.6 months ) , with a hazard ratio of 0.64 ( P=0.036 ) . Overall survival ( OS ) for gemcitabine and S-1 combination was longer than that for gemcitabine monotherapy ( 13.5 vs 8.8 months ) , with a hazard ratio of 0.72 ( P=0.104 ) . Overall , grade 3 or 4 adverse events were similar in both arms . Conclusion : Gemcitabine and S-1 combination therapy  demonstrated longer PFS in advanced pancreatic cancer . Improved OS duration of 4.7 months was found for gemcitabine and S-1 combination therapy , though this was not statistically significant Abstract Purpose To evaluate the efficacy and safety of combined gemcitabine and S-1 as first-line chemotherapy for patients with locally advanced or metastatic pancreatic cancer . Methods This study included patients who had been diagnosed with unresectable , locally advanced or metastatic adenocarcinoma arising from the pancreas , which was histologically or cytologically confirmed and involved at least 1 unidimensionally measurable lesion . The regimen consisted of intravenous 1,000 mg/m2 gemcitabine on day 1 and 8 combined with oral S-1 on days 1–14 every 21 days . The dosage of S-1 was based on the body surface area ( BSA ) as follows : 40 mg bid ( total 80 mg/day ) for a BSA of < 1.25 , 50 mg bid ( total 100 mg/day ) for a BSA of ≥1.25 but < 1.5 , and 60 mg bid ( total 120 mg/day ) for a BSA of ≥1.5 . Treatment consisted of at least 2 courses unless rapid disease progression was noted . The primary end points were the response and disease control rates , and the secondary end points were toxicity and survival . Results Thirty-seven patients were enrolled between August 2005 and December 2010 . The median number of chemotherapy cycles was 4 ( range 1–28 cycles ) . Response to treatment could be evaluated in 31 patients . None of the patients showed complete response , but 5 achieved partial response . The response rate was thus 13.5 % [ 95 % confidence interval ( CI ) 2.7–24.3 % ] in the intent-to-treat population . Sixteen patients ( 43.2 % ; 95 % CI 27–59.5 % ) showed stable disease , and the overall disease control rate was 56.8 % ( 95 % CI 40.6–72.9 % ) . For all 37 patients , the median progression-free survival was 4.6 months ( 95 % CI 1.8–7.6 month ) , and the median overall survival was 9.4 month ( 95 % CI 5.8–12.6 month ) . Chemotherapy-related grade 3/4 hematological toxicities were neutropenia ( 36.1 % ) , leucopenia ( 22.2 % ) , and anemia ( 13.9 % ) . The non-hematological toxicities were generally mild . Conclusions Combination chemotherapy with gemcitabine and S-1 was effective , convenient , and safe in patients with advanced pancreatic cancer PURPOSE The purpose of this trial was to evaluate the role of radiation therapy with concurrent gemcitabine ( GEM ) compared with GEM alone in patients with localized unresectable pancreatic cancer . PATIENTS AND METHODS Patients with localized unresectable adenocarcinoma of the pancreas were r and omly assigned to receive GEM alone ( at 1,000 mg/m(2)/wk for weeks 1 to 6 , followed by 1 week rest , then for 3 of 4 weeks ) or GEM ( 600 mg/m(2)/wk for weeks 1 to 5 , then 4 weeks later 1,000 mg/m(2 ) for 3 of 4 weeks ) plus radiotherapy ( starting on day 1 , 1.8 Gy/Fx for total of 50.4 Gy ) . Measurement of quality of life using the Functional Assessment of Cancer Therapy-Hepatobiliary question naire was also performed . RESULTS Of 74 patients entered on trial and r and omly assigned to receive GEM alone ( arm A ; n = 37 ) or GEM plus radiation ( arm B ; n = 34 ) , patients in arm B had greater incidence of grade s 4 and 5 toxicities ( 41 % v 9 % ) , but grade s 3 and 4 toxicities combined were similar ( 77 % in A v 79 % in B ) . No statistical differences were seen in quality of life measurements at 6 , 15 to 16 , and 36 weeks . The primary end point was survival , which was 9.2 months ( 95 % CI , 7.9 to 11.4 months ) and 11.1 months ( 95 % CI , 7.6 to 15.5 months ) for arms A and B , respectively ( one-sided P = .017 by stratified log-rank test ) . CONCLUSION This trial demonstrates improved overall survival with the addition of radiation therapy to GEM in patients with localized unresectable pancreatic cancer , with acceptable toxicity Purpose The aim of this study was to evaluate efficacy and safety of gemcitabine plus S-1 ( GS ) combination chemotherapy in patients with unresectable pancreatic cancer . Methods Patients were r and omly assigned to receive GS ( oral S-1 60 mg/m2 daily on days 1–15 every 3 weeks and gemcitabine 1,000 mg/m2 on days 8 and 15 ) or gemcitabine ( 1,000 mg/m2 on days 1 , 8 , and 15 every 4 weeks ) . The primary endpoint was progression-free survival ( PFS ) . Results One hundred and one patients were r and omly assigned . PFS was significantly longer in the GS arm with an estimated hazard ratio ( HR ) of 0.65 ( 95 % CI 0.43–0.98 ; P = 0.039 ; median 5.3 vs 3.8 months ) . Objective response rate ( ORR ) was also better in the GS arm ( 21.6 vs 6 % , P = 0.048 ) . Median survival was 8.6 months for GS and 8.6 months for GEM ( HR 0.93 ; 95 % CI 0.61–1.41 ; P = 0.714 ) . Grade 3–4 neutropenia ( 44 vs 19.6 % , P = 0.011 ) and thrombocytopenia ( 26 vs 8.7 % , P = 0.051 ) were more frequent in the GS arm . Conclusions GS therapy improved PFS and ORR with acceptable toxicity profile in patients with unresectable pancreatic cancer PURPOSE Most patients with advanced pancreas cancer experience pain and must limit their daily activities because of tumor-related symptoms . To date , no treatment has had a significant impact on the disease . In early studies with gemcitabine , patients with pancreas cancer experienced an improvement in disease-related symptoms . Based on those findings , a definitive trial was performed to assess the effectiveness of gemcitabine in patients with newly diagnosed advanced pancreas cancer . PATIENTS AND METHODS One hundred twenty-six patients with advanced symptomatic pancreas cancer completed a lead-in period to characterize and stabilize pain and were r and omized to receive either gemcitabine 1,000 mg/m2 weekly x 7 followed by 1 week of rest , then weekly x 3 every 4 weeks thereafter ( 63 patients ) , or to fluorouracil ( 5-FU ) 600 mg/m2 once weekly ( 63 patients ) . The primary efficacy measure was clinical benefit response , which was a composite of measurements of pain ( analgesic consumption and pain intensity ) , Karnofsky performance status , and weight . Clinical benefit required a sustained ( > or = 4 weeks ) improvement in at least one parameter without worsening in any others . Other measures of efficacy included response rate , time to progressive disease , and survival . RESULTS Clinical benefit response was experienced by 23.8 % of gemcitabine-treated patients compared with 4.8 % of 5-FU-treated patients ( P = .0022 ) . The median survival duration s were 5.65 and 4.41 months for gemcitabine-treated and 5-FU-treated patients , respectively ( P = .0025 ) . The survival rate at 12 months was 18 % for gemcitabine patients and 2 % for 5-FU patients . Treatment was well tolerated . CONCLUSION This study demonstrates that gemcitabine is more effective than 5-FU in alleviation of some disease-related symptoms in patients with advanced , symptomatic pancreas cancer .  Gemcitabine also confers a modest survival advantage over treatment with 5-FU BACKGROUND The long-term prognosis for localized pancreatic cancer ( PC ) remains poor . Three r and omized trials ( GEST phase III , JACCRO PC-01 phase II and GEMSAP phase II ) evaluated gemcitabine ( Gem ) with or without S-1 for patients with metastatic and locally advanced PC . A pooled analysis based on published data examined whether Gem with S-1 ( GS ) is superior to Gem alone in overall survival ( OS ) in patients with locally advanced PC . METHODS Data were extracted on 193 patients : 31 ( JACCRO ) , 28 ( GEMSAP ) , and 134 ( GEST ) .  OS was used for primary endpoint and progression-free survival ( PFS ) was used for secondary endpoint . A general variance-based method was used to estimate the pooled HR and 95 % CI between GS ( n = 96 ) and Gem ( n = 97 ) . RESULTS Meta- analysis demonstrated that the overall risk of death was significantly different between the two chemotherapies ( hazard ratio = 0.673 , 95 % confidence interval : 0.488 - 0.929 , P = 0.016 ) . The median PFSs for GS and GEM in the JACCRO , GEMSAP , and GEST studies 
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Discussion : Overall response rate and disease control rate as well as 1-year survival rate in patients who received GS were superior to those treated with GEM alone .
Combination chemotherapy with GEM and S-1 may offer greater benefits in the treatment of pancreatic cancer than GEM alone , although the GS group had higher haematological toxicities .
Combination chemotherapy with GEM and S-1 might be an option of first-line chemotherapy for pancreatic cancer patients , at least in Asia .
Mini Abstract : This systematic review analysing r and omized controlled trials ( RCTs ) comparing S-1 combination chemotherapy versus GEM alone for locally advanced and metastatic pancreatic cancer demonstrated greater efficacy for S-1 combination in term of response , disease control and 1-year survival proportion