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 4118 Background : Since the introduction of gemcitabine ( G ) , attempts have been made to develop G-based combination regimens to improve the dismal outcome of APC pts . Results of r and omized trials , however , have been conflicting and single-agent G presently remains the st and ard of care for such pts . METHODS All prospect i ve phase III trials comparing  single-agent G with G-based polychemotherapy regimens ( poly-G ) were considered eligible . A pooled analysis was performed and event-based relative risk ratios ( RR ) with 95 % CI were derived through both a fixed- and a r and om-effect model approach , exploring OS as the primary outcome and PFS and ORR as secondary outcomes . Heterogeneity between different trials was also taken into account . RESULTS Twelve trials involving 3682 pts were identified . The analysis was conducted considering three different subgroups : 1 ) overall population ( 3682 patients , 12 trials ) , 2 ) platinum-containing poly-G ( PG ) vs G ( 768 pts , 5 trials ) , and 3 ) fluoropyrimidine-containing poly-G ( FG ) vs G ( 1640 pts , 4 trials ) . As shown in the table , no significant differences in the primary outcome ( OS ) were observed in any of the three groups analyzed . Conversely , a significant advantage for poly-G was evident with regard to both PFS and ORR in the overall population as well as in the PG vs G subgroup , although with some heterogeneity . A heterogeneous non-significant trend towards a better PFS and ORR outcome was also observed in the FG vs G subgroup . CONCLUSIONS Single-agent G remains the treatment of choice in APC pts . However , the addition of platinum compounds to G appears to significantly improve PFS and ORR , possibly justifying the use of platinum-based poly-G in younger and fit patients . [ Table : see text ] No significant financial relationships to disclose 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 The aim was to evaluate the efficacy of gemcitabine combined with a platinum agent compared to single-agent gemcitabine in a pooled analysis of two r and omized trials . METHODS The French Multidisciplinary Clinical Research Group (GERCOR)/Italian Group for the Study of Gastrointestinal Tract Cancer ( GISCAD ) intergroup study comparing gemcitabine plus oxaliplatin to gemcitabine and a German multicenter trial comparing gemcitabine plus cisplatin versus gemcitabine were included in a pooled analysis based on individual patient data . RESULTS Among 503 evaluable patients , 252 received gemcitabine plus a platinum analog ( GP )  , while 251 patients were treated with gemcitabine alone . For progression-free survival ( PFS ) , the pooled univariate analysis indicated a hazard ratio ( HR ) of 0.75 ( P = 0.0030 ) in favour of the GP combination . The benefit from the GP combination was greatest in the subgroup of patients with performance status ( PS ) = 0 ( HR = 0.64 ; P = 0.013 ) . Also overall survival was significantly superior in patients receiving the GP combination ( HR = 0.81 ; P = 0.031 ) . Again , patients with PS = 0 appeared to have a greater benefit from treatment intensification ( HR = 0.72 ; P = 0.063 ) . CONCLUSION The pooled analysis of the GERCOR/GISCAD intergroup study and the German multicenter study indicates that the combination of gemcitabine with a platinum analog such as oxaliplatin or cisplatin significantly improves progression-free survival and overall survival as compared to single-agent gemcitabine in advanced pancreatic cancer . The benefit seems to prevail in patients with a good performance status Gemcitabine is considered the gold st and ard treatment for unresectable pancreatic adenocarcinoma . Intra-arterial drug administration had shown some interesting results in small phase II studies . In this study , patients were r and omly assigned to receive gemcitabine at a dose of 1,000 mg/m2 over 30 minutes intravenously weekly for 7 weeks , followed by 1 week of rest , then weekly for 3 weeks every 4 weeks or FLEC : 5-fluoruracil 1,000 mg/m2 , leucovorin 100 mg/m2 , epirubicin 60 mg/m2 , carboplatin 300 mg/m2 infused bolus intra-arterially into celiac axis at a 3-week interval 3 times or 5-fluorouracil 400 mg/m2 plus folinic acid 20 mg/m2 for 5 days every 4 weeks for 6 cycles . The primary endpoint was overall survival , while time to treatment failure , response rate , clinical benefit response were secondary endpoints . Sixty-seven patients were r and omly allocated gemcitabine  and 71 were allocated  FLEC  intra-arterially . Patients treated with FLEC lived for significantly longer than patients on gemcitabine ( p=0.036 ) . Survival at 1 year increased from 21 % in the gemcitabine group to 35 % in the FLEC group . Median survival was 7.9 months in the FLEC group and 5.8 months in the gemcitabine group . Median time to treatment failure was longer with FLEC ( 5.3 vs 4.2 months for FLEC vs gemcitabine respectively ; p=0.013 ) . Clinical benefit was similar in both groups ( 17.9 % for gemcitabine and 26.7 % for FLEC ; p = NS ) . CT-scan partial response was similar in both groups ( 5.9 % for gemcitabine and 14 % for FLEC ; p = NS ) . Toxicity profiles were different . Compared with gemcitabine , the FLEC regimen given intra-arterially improved survival in patients with unresectable pancreatic adenocarcinoma PURPOSE Gemcitabine is generally considered to constitute first-line therapy for pancreatic cancer . To determine whether the addition of fluorouracil ( 5-FU ) improves on the results from single-agent gemcitabine , the Eastern Cooperative Oncology Group ( ECOG ) compared gemcitabine plus bolus 5-FU with gemcitabine alone for patients with advanced pancreatic carcinoma . PATIENTS AND METHODS This trial involved patients with biopsy-proven , advanced carcinoma of the pancreas not amenable to surgical resection . Patients were r and omized to receive either gemcitabine alone ( 1,000 mg/m(2)/wk ) weekly for 3 weeks of every 4 or to receive gemcitabine ( 1,000 mg/m(2)/wk ) followed by 5-FU ( 600 mg/m(2)/wk ) weekly on the same schedule . The primary end point of the trial was survival , with secondary end points of time to progression and response rate . RESULTS Of 327 patients enrolled over 18 months , 322 were eligible . Overall , the median survival was 5.4 months for gemcitabine alone and 6.7 months for gemcitabine plus 5-FU ( P = .09 ) . Progression-free survival for gemcitabine alone was 2.2 months , compared with 3.4 months for gemcitabine plus 5-FU ( P = .022 ) . Objective responses were uncommon and were observed in only 5.6 % of patients treated with gemcitabine and 6.9 % of patients treated with gemcitabine plus 5-FU . Most toxicities were hematologic or gastrointestinal ; no significant differences were noted between the two treatment arms . CONCLUSION 5-FU , administered in conjunction with gemcitabine , did not improve the median survival of patients with advanced pancreatic carcinoma compared with single-agent gemcitabine . Further studies with other combinations of gemcitabine and 5-FU are not compelling , and clinical trial re sources should address other combinations and novel agents BACKGROUND Chemotherapy is moderately efficient as a treatment for pancreatic adenocarcinoma , but patient survival and quality of life has improved with this modality in some trials . In a previous phase II trial , 5-fluorouracil ( 5-FU ) plus cisplatin ( FUP ) yielded a 26.5 % response rate and a 29 % survival rate at 1 year . The present study aim ed to compare FUP with 5-FU alone , which was the control arm in former Mayo Clinic trials . PATIENTS AND METHODS Patients with untreated cytologically or histologically proven metastatic or locally advanced adenocarcinoma of the pancreas were deemed measurable or evaluable . Chemotherapy regimens consisted of a control FU arm ( 5-FU 500 mg/m(2)/day for 5 days ) and the investigational FUP arm ( continuous 5-FU 1000 mg/m(2)/day for 5 days plus cisplatin 1 
    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 4118 Background : Since the introduction of gemcitabine ( G ) , attempts have been made to develop G-based combination regimens to improve the dismal outcome of APC pts . Results of r and omized trials , however , have been conflicting and single-agent G presently remains the st and ard of care for such pts . METHODS All prospect i ve phase III trials comparing  single-agent G with G-based polychemotherapy regimens ( poly-G ) were considered eligible . A pooled analysis was performed and event-based relative risk ratios ( RR ) with 95 % CI were derived through both a fixed- and a r and om-effect model approach , exploring OS as the primary outcome and PFS and ORR as secondary outcomes . Heterogeneity between different trials was also taken into account . RESULTS Twelve trials involving 3682 pts were identified . The analysis was conducted considering three different subgroups : 1 ) overall population ( 3682 patients , 12 trials ) , 2 ) platinum-containing poly-G ( PG ) vs G ( 768 pts , 5 trials ) , and 3 ) fluoropyrimidine-containing poly-G ( FG ) vs G ( 1640 pts , 4 trials ) . As shown in the table , no significant differences in the primary outcome ( OS ) were observed in any of the three groups analyzed . Conversely , a significant advantage for poly-G was evident with regard to both PFS and ORR in the overall population as well as in the PG vs G subgroup , although with some heterogeneity . A heterogeneous non-significant trend towards a better PFS and ORR outcome was also observed in the FG vs G subgroup . CONCLUSIONS Single-agent G remains the treatment of choice in APC pts . However , the addition of platinum compounds to G appears to significantly improve PFS and ORR , possibly justifying the use of platinum-based poly-G in younger and fit patients . [ Table : see text ] No significant financial relationships to disclose 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 The aim was to evaluate the efficacy of gemcitabine combined with a platinum agent compared to single-agent gemcitabine in a pooled analysis of two r and omized trials . METHODS The French Multidisciplinary Clinical Research Group (GERCOR)/Italian Group for the Study of Gastrointestinal Tract Cancer ( GISCAD ) intergroup study comparing gemcitabine plus oxaliplatin to gemcitabine and a German multicenter trial comparing gemcitabine plus cisplatin versus gemcitabine were included in a pooled analysis based on individual patient data . RESULTS Among 503 evaluable patients , 252 received gemcitabine plus a platinum analog ( GP )  , while 251 patients were treated with gemcitabine alone . For progression-free survival ( PFS ) , the pooled univariate analysis indicated a hazard ratio ( HR ) of 0.75 ( P = 0.0030 ) in favour of the GP combination . The benefit from the GP combination was greatest in the subgroup of patients with performance status ( PS ) = 0 ( HR = 0.64 ; P = 0.013 ) . Also overall survival was significantly superior in patients receiving the GP combination ( HR = 0.81 ; P = 0.031 ) . Again , patients with PS = 0 appeared to have a greater benefit from treatment intensification ( HR = 0.72 ; P = 0.063 ) . CONCLUSION The pooled analysis of the GERCOR/GISCAD intergroup study and the German multicenter study indicates that the combination of gemcitabine with a platinum analog such as oxaliplatin or cisplatin significantly improves progression-free survival and overall survival as compared to single-agent gemcitabine in advanced pancreatic cancer . The benefit seems to prevail in patients with a good performance status Gemcitabine is considered the gold st and ard treatment for unresectable pancreatic adenocarcinoma . Intra-arterial drug administration had shown some interesting results in small phase II studies . In this study , patients were r and omly assigned to receive gemcitabine at a dose of 1,000 mg/m2 over 30 minutes intravenously weekly for 7 weeks , followed by 1 week of rest , then weekly for 3 weeks every 4 weeks or FLEC : 5-fluoruracil 1,000 mg/m2 , leucovorin 100 mg/m2 , epirubicin 60 mg/m2 , carboplatin 300 mg/m2 infused bolus intra-arterially into celiac axis at a 3-week interval 3 times or 5-fluorouracil 400 mg/m2 plus folinic acid 20 mg/m2 for 5 days every 4 weeks for 6 cycles . The primary endpoint was overall survival , while time to treatment failure , response rate , clinical benefit response were secondary endpoints . Sixty-seven patients were r and omly allocated gemcitabine  and 71 were allocated  FLEC  intra-arterially . Patients treated with FLEC lived for significantly longer than patients on gemcitabine ( p=0.036 ) . Survival at 1 year increased from 21 % in the gemcitabine group to 35 % in the FLEC group . Median survival was 7.9 months in the FLEC group and 5.8 months in the gemcitabine group . Median time to treatment failure was longer with FLEC ( 5.3 vs 4.2 months for FLEC vs gemcitabine respectively ; p=0.013 ) . Clinical benefit was similar in both groups ( 17.9 % for gemcitabine and 26.7 % for FLEC ; p = NS ) . CT-scan partial response was similar in both groups ( 5.9 % for gemcitabine and 14 % for FLEC ; p = NS ) . Toxicity profiles were different . Compared with gemcitabine , the FLEC regimen given intra-arterially improved survival in patients with unresectable pancreatic adenocarcinoma PURPOSE Gemcitabine is generally considered to constitute first-line therapy for pancreatic cancer . To determine whether the addition of fluorouracil ( 5-FU ) improves on the results from single-agent gemcitabine , the Eastern Cooperative Oncology Group ( ECOG ) compared gemcitabine plus bolus 5-FU with gemcitabine alone for patients with advanced pancreatic carcinoma . PATIENTS AND METHODS This trial involved patients with biopsy-proven , advanced carcinoma of the pancreas not amenable to surgical resection . Patients were r and omized to receive either gemcitabine alone ( 1,000 mg/m(2)/wk ) weekly for 3 weeks of every 4 or to receive gemcitabine ( 1,000 mg/m(2)/wk ) followed by 5-FU ( 600 mg/m(2)/wk ) weekly on the same schedule . The primary end point of the trial was survival , with secondary end points of time to progression and response rate . RESULTS Of 327 patients enrolled over 18 months , 322 were eligible . Overall , the median survival was 5.4 months for gemcitabine alone and 6.7 months for gemcitabine plus 5-FU ( P = .09 ) . Progression-free survival for gemcitabine alone was 2.2 months , compared with 3.4 months for gemcitabine plus 5-FU ( P = .022 ) . Objective responses were uncommon and were observed in only 5.6 % of patients treated with gemcitabine and 6.9 % of patients treated with gemcitabine plus 5-FU . Most toxicities were hematologic or gastrointestinal ; no significant differences were noted between the two treatment arms . CONCLUSION 5-FU , administered in conjunction with gemcitabine , did not improve the median survival of patients with advanced pancreatic carcinoma compared with single-agent gemcitabine . Further studies with other combinations of gemcitabine and 5-FU are not compelling , and clinical trial re sources should address other combinations and novel agents BACKGROUND Chemotherapy is moderately efficient as a treatment for pancreatic adenocarcinoma , but patient survival and quality of life has improved with this modality in some trials . In a previous phase II trial , 5-fluorouracil ( 5-FU ) plus cisplatin ( FUP ) yielded a 26.5 % response rate and a 29 % survival rate at 1 year . The present study aim ed to compare FUP with 5-FU alone , which was the control arm in former Mayo Clinic trials . PATIENTS AND METHODS Patients with untreated cytologically or histologically proven metastatic or locally advanced adenocarcinoma of the pancreas were deemed measurable or evaluable . Chemotherapy regimens consisted of a control FU arm ( 5-FU 500 mg/m(2)/day for 5 days ) and the investigational FUP arm ( continuous 5-FU 1000 mg/m(2)/day for 5 days plus cisplatin 1 
    Output:
    