***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: This study was performed to determine the activity of adding continuous infusion ( CI ) of 5-fluorouracil ( 5-FU ) to gemcitabine ( GEM ) vs GEM alone in advanced pancreatic cancer ( APC ) . In all , 94 chemo-naïve patients with APC were r and omised to receive GEM alone ( arm A : 1000 mg m−2 per week for 7 weeks followed by a 2 week rest period , then weekly for 3 consecutive weeks out of every 4 weeks ) or in combination with CI 5-FU ( arm B : CI 5-FU 200 mg m−2 day−1 for 6 weeks followed by a 2 week rest period , then for 3 weeks every 4 weeks ) . Overall response rate ( RR ) was the primary end point and criteria for decision were planned according to the Simon 's optimal two-stage design . The overall RR was 8 % ( arm A ) and 11 % ( arm B ) ( 95 % confidence interval : 0.5–16 % and 2–22 % ) , respectively , and stable disease was 29 and 28 % . The median duration of RR was 34 weeks ( range 25–101 weeks ) for GEM and 26 weeks ( range 16–46 weeks ) for the combination . The median progression-free survival ( PFS ) was 14 weeks ( range 2–65 weeks ) and 18 weeks ( range 4–51 weeks ) , respectively . The median overall survival ( OS ) was 31 weeks ( range 1–101 weeks ) and 30 weeks ( 1–101 weeks ) . Toxicity was mild in both arms . This study does not show promising activity in terms of RR , PFS and OS for the double combination arm in APC PURPOSE This phase III trial compared the efficacy and safety of gemcitabine ( Gem ) plus capecitabine ( GemCap ) versus single-agent Gem in advanced/metastatic pancreatic cancer . PATIENTS AND METHODS Patients were r and omly assigned to receive GemCap ( oral capecitabine 650 mg/m2 twice daily on days 1 to 14 plus Gem 1,000 mg/m2 by 30-minute infusion on days 1 and 8 every 3 weeks ) or Gem ( 1,000 mg/m2 by 30-minute infusion weekly for 7 weeks , followed by a 1-week break , and then weekly for 3 weeks every 4 weeks ) . Patients were stratified according to center , Karnofsky performance score ( KPS ) , presence of pain , and disease extent . RESULTS A total of 319 patients were enrolled between June 2001 and June 2004 .  Median overall survival ( OS ) time , the primary end point , was 8.4 and 7.2 months in the GemCap and Gem arms , respectively ( P = .234 ) . Post hoc analysis in patients with good KPS ( score of 90 to 100 ) showed a significant prolongation of median OS time in the GemCap arm compared with the Gem arm ( 10.1 v 7.4 months , respectively ; P = .014 ) . The overall frequency of grade 3 or 4 adverse events was similar in each arm . Neutropenia was the most frequent grade 3 or 4 adverse event in both arms . CONCLUSION GemCap failed to improve OS at a statistically significant level compared with st and ard Gem treatment . The safety of GemCap and Gem was similar . In the subgroup of patients with good performance status , median OS was improved significantly . GemCap is a practical regimen that may be considered as an alternative to single-agent Gem for the treatment of advanced/metastatic pancreatic cancer patients with a good performance status 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 PURPOSE Our purpose in the study was to determine the maximum tolerated dose and dose-limiting toxicity and investigate the clinical pharmacology of S-1 , a combination of tegafur , 5-chloro-2,4-dihydroxypyridine ( CDHP ) , and potassium oxonate . EXPERIMENTAL DESIGN Eligible patients had advanced solid tumors , adequate organ function , and no anticancer therapy in the preceding 4 weeks . Dose level 1 was 30 mg/m(2)/dose , level 2 was 40 mg/m(2)/dose , and level 3 was 35 allmg/m(2)/dose , all of the levels comprising two daily doses . S-1 was administered as a single dose at each level , and its pharmacology was studied . The first course was begun 3 days later and consisted of 28 consecutive treatment days , followed by a 1-week rest . RESULTS Sixteen patients were enrolled ;  toxicity could be assessed in all of the 16 and response in 15 . At dose level 1 , two of nine patients developed grade 3 hyperbilirubinemia or diarrhea . Dose-limiting toxicity ( diarrhea ) occurred in all three of the patients at dose level 2 . The protocol was , therefore , amended to include an intermediate dose level ( level 3 ) , which caused grade 3 or 4 diarrhea or hyperbilirubinemia in three of four patients . Dose level 1 was thus considered as the maximum tolerated dose . Other grade 3 or 4 toxic effects at dose level 2 or 3 were granulocytopenia , nausea , and vomiting . The pharmacology of tegafur , CDHP , potassium oxonate , and fluorouracil ( a metabolite of tegafur ) was characterized by rapid absorption and was consistent with first-order kinetics . One patient with colorectal cancer had a durable partial response . CONCLUSIONS The recommended S-1 dose for future studies is 30 mg/m(2 ) twice daily , and diarrhea is the most frequent toxic effect . Additional trials of S-1 in the treatment of patients with solid tumors are warranted Three hundred five patients with advanced pancreatic and gastric carcinoma were r and omly assigned to treatment with fluorouracil , fluorouracil plus doxorubicin ( Adriamycin ) ( FA ) , or fluorouracil plus doxorubicin plus mitomycin ( mitomycin C ) ( FAM ) . All regimens were equivalent with regard to patient survival . There is no reasonable likelihood that either the FA or FAM regimen could produce a meaningful survival advantage over fluorouracil alone . Interval to disease progression , objective response rates , and palliative effects ( improved performance , body weight , or symptoms ) were essentially equivalent among the three regimens . With regard to toxicity , the FAM regimen produced more anorexia , nausea , vomiting , leukopenia , thrombocytopenia , and cumulative bone marrow suppression . Fluorouracil alone produced more stomatitis and diarrhea . Because of a failure to produce improved survival or palliation , unrewarded toxicity , and excessive cost , neither the FA nor FAM regimen can be recommended for the treatment of advanced pancreatic or gastric cancer 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 PURPOSE To compare clinical benefit response ( CBR ) and quality of life ( QOL ) in patients receiving gemcitabine ( Gem ) plus capecitabine ( Cap ) versus  single-agent Gem for advanced/metastatic pancreatic cancer . PATIENTS AND METHODS Patients were r and omly assigned to receive GemCap ( oral Cap 650 mg/m(2 ) twice daily on days 1 through 14 plus Gem 1,000 mg/m(2 ) in a 30-minute infusion on days 1 and 8 every 3 weeks ) or Gem ( 1,000 mg/m(2 ) in a 30-minute infusion weekly for 7 weeks , followed by a 1-week break , and then weekly for 3 weeks every 4 weeks ) for 24 weeks or until progression . CBR criteria and QOL indicators were assessed over this period . CBR was defined as improvement from baseline for > or= 4 consecutive weeks in pain ( pain intensity or analgesic consumption ) and Karnofsky performance status , stability in one but improvement in the other , or stability in pain and performance status but improvement in weight . RESULTS Of 319 patients , 19 % treated with GemCap and 20 % treated with Gem experienced a CBR , with a median duration of 9.5 and 6.5 weeks , respectively ( P < .02 ) ; 54 % of patients treated with GemCap and 60 % treated with Gem had no CBR ( remaining patients were not assessable ) . There was no treatment difference in QOL ( n = 311 ) . QOL indicators were improving under chemotherapy ( P < .05 ) . These changes differed by the time to failure , with a worsening 1 to 2 months before treatment failure ( all P < .05 ) . CONCLUSION There is no indication of a difference in CBR or QOL between GemCap and Gem . Regardless of their initial condition , some patients experience an improvement in QOL on chemotherapy , followed by a worsening before treatment failure 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 
    Output:
    
CONCLUSIONS Gemcitabine combination therapy provides a modest improvement of survival , but is associated with more toxicity compared with gemcitabine monotherapy