***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 BACKGROUND In a phase 1 - 2 trial of albumin-bound paclitaxel ( nab-paclitaxel ) plus gemcitabine , substantial clinical activity was noted in patients with advanced pancreatic cancer . We conducted a phase 3 study of the efficacy and safety of the combination versus gemcitabine monotherapy in patients with metastatic pancreatic cancer . METHODS We r and omly assigned patients with a Karnofsky performance-status score of 70 or more ( on a scale from 0 to 100 , with higher scores indicating better performance status ) to nab-paclitaxel ( 125 mg per square meter of body-surface area ) followed by gemcitabine  ( 1000 mg per square meter ) on days 1 , 8 , and 15 every 4 weeks or gemcitabine monotherapy ( 1000 mg per square meter ) weekly for 7 of 8 weeks ( cycle 1 ) and then on days 1 , 8 , and 15 every 4 weeks ( cycle 2 and subsequent cycles ) . Patients received the study treatment until disease progression . The primary end point was overall survival ; secondary end points were progression-free survival and overall response rate . RESULTS A total of 861 patients were r and omly assigned to nab-paclitaxel plus gemcitabine ( 431 patients ) or gemcitabine  ( 430 ) . The median overall survival was 8.5 months in the nab-paclitaxel-gemcitabine group as compared with 6.7 months in the gemcitabine group ( hazard ratio for death , 0.72 ; 95 % confidence interval [ CI ] , 0.62 to 0.83 ; P<0.001 ) . The survival rate was 35 % in the nab-paclitaxel-gemcitabine group versus 22 % in the gemcitabine group at 1 year , and 9 % versus 4 % at 2 years . The median progression-free survival was 5.5 months in the nab-paclitaxel-gemcitabine group , as compared with 3.7 months in the gemcitabine group ( hazard ratio for disease progression or death , 0.69 ; 95 % CI , 0.58 to 0.82 ; P<0.001 ) ; the response rate according to independent review was 23 % versus 7 % in the two groups ( P<0.001 ) . The most common adverse events of grade 3 or higher were neutropenia ( 38 % in the nab-paclitaxel-gemcitabine group vs. 27 % in the gemcitabine group ) , fatigue ( 17 % vs. 7 % ) , and neuropathy ( 17 % vs. 1 % ) . Febrile neutropenia occurred in 3 % versus 1 % of the patients in the two groups . In the nab-paclitaxel-gemcitabine group , neuropathy of grade 3 or higher improved to grade 1 or lower in a median of 29 days . CONCLUSIONS In patients with metastatic pancreatic adenocarcinoma , nab-paclitaxel plus gemcitabine significantly improved overall survival , progression-free survival , and response rate , but rates of peripheral neuropathy and myelosuppression were increased . ( Funded by Celgene ; Clinical Trials.gov number , NCT00844649 . ) 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 ) . 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 The combination of gemcitabine plus bevacizumab produced a 21 % response rate and a median survival of 8.8 months in a multicenter phase II trial in patients with metastatic pancreatic cancer . These encouraging data led Cancer and Leukemia Group B ( CALGB ) to conduct a double-blind , placebo-controlled , r and omized phase III trial of gemcitabine/bevacizumab versus gemcitabine/placebo in advanced pancreatic cancer patients . PATIENTS AND METHODS Eligible patients had no prior therapy for advanced disease , Eastern Cooperative Oncology Group ( ECOG ) performance status 0 to 2 , no tumor invasion of adjacent organs , and no increased bleeding risk . The primary end point was overall survival . Patients were stratified by performance status , extent of disease , and prior radiotherapy . Patients received gemcitabine at 1,000 mg/m(2 ) over 30 minutes on days 1 , 8 , and 15 every 28 days and bevacizumab at 10 mg/kg or placebo on days 1 and 15 every 28 days . RESULTS Between June 2004 and April 2006 , 602 patients were enrolled onto the study and 535 were treated .  Median overall survival was 5.8 months for gemcitabine/bevacizumab and 5.9 months for gemcitabine/placebo ( P = .95 ) . Median progression-free survival was 3.8 and 2.9 months , respectively ( P = .07 ) . Overall response rates were 13 % and 10 
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However , the combination of gemcitabine with other cytotoxic agents , such as platinum compounds or topoisomerase inhibitors failed to reduce the mortality risk .
Combination therapy caused more grade 3/4 toxicities , including neutropenia , thrombocytopenia , vomiting , diarrhea , and fatigue .
Conclusions Gemcitabine-based doublet regimens demonstrated superiority over gemcitabine monotherapy in overall efficacy , but were associated with increased toxicity .
Different gemcitabine-based combinations showed different antitumor activity , and doublet regimens of gemcitabine in combination with a taxoid or a fluoropyrimidine , in particular an oral fluoropyrimidine provided significant survival benefits in the first-line treatment of unresectable LA/MPC