human
***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 Pancreatic cancer is the fifth most common cause of cancer death in the western world and the prognosis for unresectable disease remains poor . Recent advances in conventional chemotherapy and the development of novel ‘ molecular ’ treatment strategies with different toxicity profiles warrant investigation as combination treatment strategies . This r and omised study in pancreatic cancer compares marimastat ( orally administered matrix metalloproteinase inhibitor ) in combination with gemcitabine to gemcitabine alone .  Two hundred and thirty-nine patients with unresectable pancreatic cancer were r and omised to receive gemcitabine ( 1000 mg m−2 ) in combination with either marimastat or placebo . The primary end-point was survival . Objective tumour response and duration of response , time to treatment failure and disease progression , quality of life and safety were also assessed . There was no significant difference in survival between gemcitabine and marimastat and gemcitabine and placebo ( P=0.95 log-rank test ) . Median survival times were 165.5 and 164 days and 1-year survival was 18 % and 17 % respectively . There were no significant differences in overall response rates ( 11 and 16 % respectively ) , progression-free survival ( P=0.68 log-rank test ) or time to treatment failure ( P=0.70 log-rank test ) between the treatment arms . The gemcitabine and marimastat combination was well tolerated with only 2.5 % of patients withdrawn due to presumed marimastat toxicity . Grade 3 or 4 musculoskeletal toxicities were reported in only 4 % of the marimastat treated patients , although 59 % of marimastat treated patients reported some musculoskeletal events . The results of this study provide no evidence to support a combination of marimastat with gemcitabine in patients with advanced pancreatic cancer . The combination of marimastat with gemcitabine was well tolerated . Further studies of marimastat as a maintenance treatment following a response or stable disease on gemcitabine may be justified Background : To evaluate the efficacy and tolerability of the urokinase plasminogen activator ( uPA ) inhibitor upamostat in combination with gemcitabine in locally advanced pancreatic adenocarcinoma ( LAPC ) . Methods : Within a prospect i ve multicenter study , LAPC patients were r and omly assigned to receive 1000 mg m−2 of gemcitabine IV weekly either alone ( arm A ) or in combination with 200 mg ( arm B ) or 400 mg ( arm C ) oral upamostat daily . Efficacy endpoints of this proof-of-concept study included response rate , time to first metastasis , progression-free and overall survival ( OS ) . Results : Of the 95 enroled patients , 85 were evaluable for response and 93 for safety . Median OS was 12.5 months ( 95 % CI 8.2–18.2 ) in arm C , 9.7 months ( 95 % CI 8.4–17.1 ) in arm B and 9.9 months ( 95 % CI 7.4–12.1 ) in arm A ; corresponding 1-year survival rates were 50.6 % , 40.7 % and 33.9 % , respectively . More patients achieved a partial remission ( confirmed responses by RECIST ) with upamostat combination therapy ( arm C : 12.9 % ; arm B : 7.1 % ; arm A : 3.8 % ) . Overall , only 12 patients progressed by developing detectable distant metastasis ( arm A : 4 , arm B : 6 , arm C : 2 ) . The most common adverse events considered to be related to upamostat  were asthenia , fever and nausea . Conclusion : In this proof-of-concept study targeting the uPA system in LAPC , the addition of upamostat to gemcitabine was tolerated well ; similar survival results were observed for the three treatment arms Background : Only a few clinical trials have been conducted in patients with advanced pancreatic cancer after failure of first-line gemcitabine-based chemotherapy . Therefore , there is no current consensus on the treatment of these patients . We conducted a r and omised phase II study of the modified FOLFIRI.3 ( mFOLFIRI.3 ; a regimen combining 5-fluorouracil ( 5-FU ) , folinic acid , and irinotecan ) and modified FOLFOX ( mFOLFOX ; a regimen combining folinic acid , 5-FU , and oxaliplatin ) regimens as second-line treatments in patients with gemcitabine-refractory pancreatic cancer . Methods : The primary end point was the 6-month overall survival rate . The mFOlFIRI.3 regimen consisted of irinotecan ( 70 mg m−2 ; days 1 and 3 ) , leucovorin ( 400 mg m−2 ; day 1 ) , and 5-FU ( 2000 mg m−2 ; days 1 and 2 ) every 2 weeks . The mFOLFOX regimen was composed of oxaliplatin ( 85 mg m−2 ; day 1 ) , leucovorin ( 400 mg m−2 ; day 1 ) , and 5-FU ( 2000 mg m−2 ; days 1 and 2 ) every 2 weeks . Results : Sixty-one patients were r and omised to mFOLFIRI.3 ( n=31 ) or mFOLFOX ( n=30 ) regimen .  The six-month survival rates were 27 % ( 95 % confidence interval (CI)=13–46 % ) and 30 % ( 95 % CI=15–49 % ) , respectively . The median overall survival periods were 16.6 and 14.9 weeks , respectively . Disease control was achieved in 23 % ( 95 % CI=10–42 % ) and 17 % patients ( 95 % CI=6–35 % ) , respectively . The number of patients with at least one grade 3/4 toxicity was identical ( 11 patients , 38 % ) in both groups : neutropenia ( 7 patients under mFOLFIRI.3 regimen vs 6 patients under mFOLFOX regimen ) , asthaenia ( 1 vs 4 ) , vomiting ( 3 in both ) , diarrhoea ( 2 vs 0 ) , and mucositis ( 1 vs 2 ) . Conclusion : Both mFOLFIRI.3 and mFOLFOX regimens were tolerated with manageable toxicity , offering modest activities as second-line treatments for patients with advanced pancreatic cancer , previously treated with gemcitabine Background Anti-angiogenic treatment is believed to have at least cystostatic effects in highly vascularized tumours like pancreatic cancer . In this study , the treatment effects of the angiogenesis inhibitor Cilengitide and gemcitabine were compared with gemcitabine alone in patients with advanced unresectable pancreatic cancer . Methods A multi-national , open-label , controlled , r and omized , parallel-group , phase II pilot study was conducted in 20 centers in 7 countries .  Cilengitide was administered at 600 mg/m2 twice weekly for 4 weeks per cycle and gemcitabine at 1000 mg/m2 for 3 weeks followed by a week of rest per cycle . The planned treatment period was 6 four-week cycles . The primary endpoint of the study was overall survival and the secondary endpoints were progression-free survival ( PFS ) , response rate , quality of life ( QoL ) , effects on biological markers of disease ( CA 19.9 ) and angiogenesis ( vascular endothelial growth factor and basic fibroblast growth factor ) , and safety . An ancillary study investigated the pharmacokinetics of both drugs in a subset of patients . Results Eighty-nine patients were r and omized . The median overall survival was 6.7 months for Cilengitide and gemcitabine and 7.7 months for gemcitabine alone . The median PFS times were 3.6 months and 3.8 months , respectively . The overall response rates were 17 % and 14 % , and the tumor growth control rates were 54 % and 56 % , respectively . Changes in the levels of CA 19.9 went in line with the clinical course of the disease , but no apparent relationships were seen with the biological markers of angiogenesis . QoL and safety evaluations were comparable between treatment groups . Pharmacokinetic studies showed no influence of gemcitabine on the pharmacokinetic parameters of Cilengitide and vice versa . Conclusion There were no clinical ly important differences observed regarding efficacy , safety and QoL between the groups . The observations lay in the range of other clinical studies in this setting . The combination regimen was well tolerated with no adverse effects on the safety , tolerability and pharmacokinetics of either agent In a r and omized trial we compared single-agent epirubicin with the FEM ( 5-fluorouracil/epirubicin/mitomycin ) combination in patients with locally advanced and /or metastatic adenocarcinoma of the pancreas . Sixty patients previously untreated with radiotherapy or chemotherapy  were r and omly assigned to receive either 100 mg/m2 epirubicin or FEM in the following doses : 5-fluorouracil , 600 mg/m2 to a maximum of 1 g ; epirubicin , 50 mg/m2 ; mitomycin , 6 mg/m2 to a maximum of 10 mg . Treatment was given every 28 days via intravenous bolus ; because of its association with delayed myelotoxicity , mitomycin was given every other cycle . A total of 47 patients are evaluable for toxicity and survival  , 22 who received FEM and 25 epirubicin . Preliminary results of this ongoing study show no difference in survival between the two arms . Toxicity has been easily managed . A similar number of patients in each arm had elevated serum bilirubin levels , but dose reductions of 50 % allowed all these patients to continue treatment In this multicenter r and omized trial , the efficacy of combination chemotherapy using 5-fluorouracil , doxorub 
    Output:
    
agent
***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 Pancreatic cancer is the fifth most common cause of cancer death in the western world and the prognosis for unresectable disease remains poor . Recent advances in conventional chemotherapy and the development of novel ‘ molecular ’ treatment strategies with different toxicity profiles warrant investigation as combination treatment strategies . This r and omised study in pancreatic cancer compares marimastat ( orally administered matrix metalloproteinase inhibitor ) in combination with gemcitabine to gemcitabine alone .  Two hundred and thirty-nine patients with unresectable pancreatic cancer were r and omised to receive gemcitabine ( 1000 mg m−2 ) in combination with either marimastat or placebo . The primary end-point was survival . Objective tumour response and duration of response , time to treatment failure and disease progression , quality of life and safety were also assessed . There was no significant difference in survival between gemcitabine and marimastat and gemcitabine and placebo ( P=0.95 log-rank test ) . Median survival times were 165.5 and 164 days and 1-year survival was 18 % and 17 % respectively . There were no significant differences in overall response rates ( 11 and 16 % respectively ) , progression-free survival ( P=0.68 log-rank test ) or time to treatment failure ( P=0.70 log-rank test ) between the treatment arms . The gemcitabine and marimastat combination was well tolerated with only 2.5 % of patients withdrawn due to presumed marimastat toxicity . Grade 3 or 4 musculoskeletal toxicities were reported in only 4 % of the marimastat treated patients , although 59 % of marimastat treated patients reported some musculoskeletal events . The results of this study provide no evidence to support a combination of marimastat with gemcitabine in patients with advanced pancreatic cancer . The combination of marimastat with gemcitabine was well tolerated . Further studies of marimastat as a maintenance treatment following a response or stable disease on gemcitabine may be justified Background : To evaluate the efficacy and tolerability of the urokinase plasminogen activator ( uPA ) inhibitor upamostat in combination with gemcitabine in locally advanced pancreatic adenocarcinoma ( LAPC ) . Methods : Within a prospect i ve multicenter study , LAPC patients were r and omly assigned to receive 1000 mg m−2 of gemcitabine IV weekly either alone ( arm A ) or in combination with 200 mg ( arm B ) or 400 mg ( arm C ) oral upamostat daily . Efficacy endpoints of this proof-of-concept study included response rate , time to first metastasis , progression-free and overall survival ( OS ) . Results : Of the 95 enroled patients , 85 were evaluable for response and 93 for safety . Median OS was 12.5 months ( 95 % CI 8.2–18.2 ) in arm C , 9.7 months ( 95 % CI 8.4–17.1 ) in arm B and 9.9 months ( 95 % CI 7.4–12.1 ) in arm A ; corresponding 1-year survival rates were 50.6 % , 40.7 % and 33.9 % , respectively . More patients achieved a partial remission ( confirmed responses by RECIST ) with upamostat combination therapy ( arm C : 12.9 % ; arm B : 7.1 % ; arm A : 3.8 % ) . Overall , only 12 patients progressed by developing detectable distant metastasis ( arm A : 4 , arm B : 6 , arm C : 2 ) . The most common adverse events considered to be related to upamostat  were asthenia , fever and nausea . Conclusion : In this proof-of-concept study targeting the uPA system in LAPC , the addition of upamostat to gemcitabine was tolerated well ; similar survival results were observed for the three treatment arms Background : Only a few clinical trials have been conducted in patients with advanced pancreatic cancer after failure of first-line gemcitabine-based chemotherapy . Therefore , there is no current consensus on the treatment of these patients . We conducted a r and omised phase II study of the modified FOLFIRI.3 ( mFOLFIRI.3 ; a regimen combining 5-fluorouracil ( 5-FU ) , folinic acid , and irinotecan ) and modified FOLFOX ( mFOLFOX ; a regimen combining folinic acid , 5-FU , and oxaliplatin ) regimens as second-line treatments in patients with gemcitabine-refractory pancreatic cancer . Methods : The primary end point was the 6-month overall survival rate . The mFOlFIRI.3 regimen consisted of irinotecan ( 70 mg m−2 ; days 1 and 3 ) , leucovorin ( 400 mg m−2 ; day 1 ) , and 5-FU ( 2000 mg m−2 ; days 1 and 2 ) every 2 weeks . The mFOLFOX regimen was composed of oxaliplatin ( 85 mg m−2 ; day 1 ) , leucovorin ( 400 mg m−2 ; day 1 ) , and 5-FU ( 2000 mg m−2 ; days 1 and 2 ) every 2 weeks . Results : Sixty-one patients were r and omised to mFOLFIRI.3 ( n=31 ) or mFOLFOX ( n=30 ) regimen .  The six-month survival rates were 27 % ( 95 % confidence interval (CI)=13–46 % ) and 30 % ( 95 % CI=15–49 % ) , respectively . The median overall survival periods were 16.6 and 14.9 weeks , respectively . Disease control was achieved in 23 % ( 95 % CI=10–42 % ) and 17 % patients ( 95 % CI=6–35 % ) , respectively . The number of patients with at least one grade 3/4 toxicity was identical ( 11 patients , 38 % ) in both groups : neutropenia ( 7 patients under mFOLFIRI.3 regimen vs 6 patients under mFOLFOX regimen ) , asthaenia ( 1 vs 4 ) , vomiting ( 3 in both ) , diarrhoea ( 2 vs 0 ) , and mucositis ( 1 vs 2 ) . Conclusion : Both mFOLFIRI.3 and mFOLFOX regimens were tolerated with manageable toxicity , offering modest activities as second-line treatments for patients with advanced pancreatic cancer , previously treated with gemcitabine Background Anti-angiogenic treatment is believed to have at least cystostatic effects in highly vascularized tumours like pancreatic cancer . In this study , the treatment effects of the angiogenesis inhibitor Cilengitide and gemcitabine were compared with gemcitabine alone in patients with advanced unresectable pancreatic cancer . Methods A multi-national , open-label , controlled , r and omized , parallel-group , phase II pilot study was conducted in 20 centers in 7 countries .  Cilengitide was administered at 600 mg/m2 twice weekly for 4 weeks per cycle and gemcitabine at 1000 mg/m2 for 3 weeks followed by a week of rest per cycle . The planned treatment period was 6 four-week cycles . The primary endpoint of the study was overall survival and the secondary endpoints were progression-free survival ( PFS ) , response rate , quality of life ( QoL ) , effects on biological markers of disease ( CA 19.9 ) and angiogenesis ( vascular endothelial growth factor and basic fibroblast growth factor ) , and safety . An ancillary study investigated the pharmacokinetics of both drugs in a subset of patients . Results Eighty-nine patients were r and omized . The median overall survival was 6.7 months for Cilengitide and gemcitabine and 7.7 months for gemcitabine alone . The median PFS times were 3.6 months and 3.8 months , respectively . The overall response rates were 17 % and 14 % , and the tumor growth control rates were 54 % and 56 % , respectively . Changes in the levels of CA 19.9 went in line with the clinical course of the disease , but no apparent relationships were seen with the biological markers of angiogenesis . QoL and safety evaluations were comparable between treatment groups . Pharmacokinetic studies showed no influence of gemcitabine on the pharmacokinetic parameters of Cilengitide and vice versa . Conclusion There were no clinical ly important differences observed regarding efficacy , safety and QoL between the groups . The observations lay in the range of other clinical studies in this setting . The combination regimen was well tolerated with no adverse effects on the safety , tolerability and pharmacokinetics of either agent In a r and omized trial we compared single-agent epirubicin with the FEM ( 5-fluorouracil/epirubicin/mitomycin ) combination in patients with locally advanced and /or metastatic adenocarcinoma of the pancreas . Sixty patients previously untreated with radiotherapy or chemotherapy  were r and omly assigned to receive either 100 mg/m2 epirubicin or FEM in the following doses : 5-fluorouracil , 600 mg/m2 to a maximum of 1 g ; epirubicin , 50 mg/m2 ; mitomycin , 6 mg/m2 to a maximum of 10 mg . Treatment was given every 28 days via intravenous bolus ; because of its association with delayed myelotoxicity , mitomycin was given every other cycle . A total of 47 patients are evaluable for toxicity and survival  , 22 who received FEM and 25 epirubicin . Preliminary results of this ongoing study show no difference in survival between the two arms . Toxicity has been easily managed . A similar number of patients in each arm had elevated serum bilirubin levels , but dose reductions of 50 % allowed all these patients to continue treatment In this multicenter r and omized trial , the efficacy of combination chemotherapy using 5-fluorouracil , doxorub 
    Output:
    