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: BACKGROUND This r and omised study compared protracted venous infusion ( PVI ) fluorouracil ( 5-FU ) with PVI 5-FU plus mitomycin C ( MMC ) in patients with advanced oesophago-gastric cancer . PATIENTS AND METHODS Two hundred and fifty-four patients with adenocarcinoma , squamous cell carcinoma or undifferentiated carcinoma involving the oesophagus , oesophago-gastric junction or the stomach were r and omised . The major end points were tumour response , survival , toxicity and quality of life . RESULTS The median age of patients treated was 72 years and the two arms were well-balanced for baseline demographic factors . The overall response rate was 16.1 % [ 95 % confidence interval ( CI ) 9.5 % to 22.7 % ] in patients treated with PVI 5-FU alone compared with 19.1 % ( 95 % CI 12.0 % to 26.0 % ) for those treated with PVI 5-FU plus MMC ( P = 0.555 ) . Median time to treatment failure was 3.9 months for PVI 5-FU and 3.8 months for PVI 5-FU plus MMC ( P = 0.195 ) . Median survival was 6.3 months for PVI 5-FU and 5.3 months for PVI 5-FU plus MMC ( P = 1.0 ) . Toxicity was mild for both treatments . Symptomatic benefit measured by improvement in pain control , weight loss , dysphagia and oesophageal reflux was observed in over 64 % of patients in each arm . Quality of life scores were comparable in each arm . CONCLUSIONS PVI 5-FU is a safe , effective form of palliation for patients with advanced oesophago-gastric cancer although the addition of MMC adds little extra benefit We report the final results of a prospect ively r and omized study that compared the combination of epirubicin , cisplatin and protracted venous infusion fluorouracil ( 5-FU ) ( ECF regimen ) with the st and ard combination of 5-FU , doxorubicin and methotrexate ( FAMTX ) in previously untreated patients with advanced oesophagogastric cancer . Between 1992 and 1995 , 274 patients with adenocarcinoma or undifferentiated carcinoma were r and omized from eight oncology centres in the UK and analysed for response and survival . The overall response rate was 46 % ( 95 % confidence interval ( CI ) , 37–55 % ) with ECF , and 21 % ( 95 % CI , 13–28 % ) with FAMTX ( P = 0.00003 ) . The median survival was 8.7 months with ECF and 6.1 months with FAMTX ( P = 0.0005 ) . The 2-year survival rates were 14 % ( 95 % CI , 8–20 % ) for the ECF arm , and 5 % ( 95 % CI , 2–10 % ) for the FAMTX arm ( P = 0.03 ) . Histologically complete surgical resection following chemotherapy was achieved in ten patients in the ECF arm ( three pathological complete responses to chemotherapy ) and three patients in the FAMTX arm ( no pathological complete responses ) . The ECF regimen result ed in a response and survival advantage compared with FAMTX chemotherapy . The probability of long-term survival following surgical resection of residual disease is increased by this treatment . The high response rates seen with ECF support its use in the neoadjuvant setting Importance Dysregulation of the mesenchymal-epithelial transition ( MET ) signaling pathway is associated with poor prognosis in gastroesophageal adenocarcinoma ( GEC ) . We report results of METGastric , a phase 3 trial of the MET inhibitor onartuzumab plus st and ard first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative , MET-positive , advanced GEC . Objective To determine whether the addition of onartuzumab to first-line fluorouracil , leucovorin , and oxaliplatin ( mFOLFOX6 ) improves efficacy compared with mFOLFOX6 plus placebo in HER2-negative , MET-positive GEC . Design , Setting , and Participants R and omized , double-blind , multicenter trial conducted from November 2012 to March 2014 . Patients were 18 years or older with an adenocarcinoma of the stomach or gastroesophageal junction with metastatic disease not amenable for curative therapy . Tumor sample s were central ly tested for MET expression using Ventana anti-Total c-MET ( SP44 ) rabbit monoclonal antibody , HER2 status , and Lauren histologic subtype . MET-positive tumors were defined as at least 50 % of tumor cells showing weak , moderate , and /or strong staining intensity ( MET 1+/2+/3 + , respectively ) by immunohistochemistry . Interventions Patients with HER2-negative , MET-positive GEC were enrolled and r and omized 1:1 to receive mFOLFOX6 with or without onartuzumab ( 10 mg/kg ) . Main Outcomes and Measures Co– primary end points : overall survival in the intent-to-treat ( ITT ) population and in patients with MET 2+/3 + GEC . Secondary end points : progression-free survival ( PFS ) , overall response rate ( ORR ) , and safety . Results Enrollment was stopped early due to sponsor decision , which was agreed with an independent data monitoring committee . At the data cutoff ( April 25 , 2014 ) there were 562 patients in the ITT population ( n = 283 placebo plus mFOLFOX6 [ median age , 58 y ; 65 % male ] ; n = 279 onartuzumab plus mFOLFOX6 [ median age , 60 y ; 67 % male ] ) ; 109 ( 38.5 % ) and 105 ( 37.6 % ) of the ITT population were MET 2+/3 + , respectively . Addition of onartuzumab to mFOLFOX6 did not significantly improve OS , PFS , or ORR vs placebo plus mFOLFOX6 in the ITT ( OS hazard ratio [ HR ] , 0.82 ; 95 % CI , 0.59 - 1.15 ; P = .24 ; PFS HR , 0.90 ; 95 % CI , 0.71 - 1.16 ; P = .43 ; ORR , 46.1 % vs 40.6 % ) or MET 2+/3 + population s ( OS HR , 0.64 ; 95 % CI , 0.40 - 1.03 ; P = .06 ; PFS HR , 0.79 ; 95 % CI , 0.54 - 1.15 ; P = .22 ; ORR , 53.8 % vs 44.6 % ) . Safety was as expected for onartuzumab . Conclusions and Relevance Addition of onartuzumab to first-line mFOLFOX6 did not significantly improve clinical benefits in the ITT or MET 2+/3 + population s. Trial Registration clinical trials.gov Identifier : OBJECTIVES More than half of cases of gastric cancer ( GC ) are diagnosed in elderly patients ( ≥70years ) . While doublet combination with fluoropyrimidines and platinum is currently considered st and ard first-line chemotherapy in advanced GC , the main goal of chemotherapy remains palliation . MATERIAL S AND METHODS In a multi-center phase III trial , patients with chemotherapy-naïve , metastatic GC , aged 70years or older were r and omized 1:1 to receive X monotherapy ( capecitabine 1000mg/m2 bid po on days one to fourteen ) or XELOX ( X plus oxaliplatin 110mg/m2 iv on D1 ) . Treatment was repeated every 21days until disease progression , unacceptable toxicity , or withdrawal . Primary endpoint was overall survival ( OS ) . RESULTS In total , 50 patients with a median age of 77 ( range , 70 to 84 ) were enrolled ( X , n=26 ; XELOX , n=24 ) . No treatment-related serious adverse events or unexpected toxicities were observed . The most frequently observed toxicities were nausea and h and -foot syndrome , with fatigue and peripheral neuropathy more common in XELOX than in X patients . Median OS was 11.1months for XELOX arm and 6.3months for X arm ( HR 0.58 , 95 % CI 0.30 - 1.12 , P=0.108 ) . Although the difference was not significant , on the basis of evidence of superiority of XELOX seen in the first interim analysis , an independent data monitoring committee recommended early stopping of the trial . PFS was significantly longer ( HR 0.32 , 95 % CI 0.17 - 0.61 , P<0.001 ) with XELOX ( 7.1months ) than with X ( 2.6months ) . CONCLUSION Platinum-based combination chemotherapy was associated with survival benefit , as compared with X monotherapy in elderly patients with GC Background : Elderly patients are commonly under-represented in cancer clinical trials . The 321GO was undertaken in preparation for a definitive phase three trial assessing different chemotherapy regimens in a frail and /or elderly population with advanced gastroesophageal ( GO ) cancer . Methods : Patients with advanced GO cancer considered unfit for conventional dose chemotherapy were r and omly assigned in a 1 : 1 : 1 ratio to : epirubicin , oxaliplatin and capecitabine ( EOX ) ; oxaliplatin and capecitabine ( OX ) ; and capecitabine alone ( X ) ( all 80 % of full dose and unblinded ) . The primary end point was patient recruitment over an 18-month period . A registration study recorded treatment choice for all patients with advanced GO cancer at trial centres . Results : A total of 313 patients were considered for palliative chemotherapy for GO cancer over the 18-month period : 115 received full dose treatment , 89 less than st and ard treatment or entered 321GO and 111 no treatment . Within 321GO , 55 patients were r and omly assigned ( 19 to OX and X ; 17 to EOX ) . Progression-free survival ( PFS ) for all patients was 4.4 months and by arm 5.4 , 5.6 and 3.0 months for EOX , OX and X , respectively . The number of patients with a good overall treatment utility ( OTU ) , a novel patient-centred endpoint , at 12 weeks was 3 ( 18 % ) , 6 ( 32 % ) and 1 ( 6 % ) for EOX , OX and X , respectively . At 6 weeks , 22 patients ( 41 % ) had experienced a non-haematologic toxicity ⩾ grade 3 , most commonly lethargy or diarrhoea . The OTU was prognostic for overall survival in patients alive at week 12 ( logrank test P=0.0001 ) . Conclusions : It is feasible to recruit elderly and /or frail patients with advanced GO cancer to a r and omised clinical trial . The OX is the preferred regimen for further study . Overall treatment utility shows promise as a comparator between treatment regimens for feasibility and r and omised trials in the elderly and /or frail GO cancer population BACKGROUND Rilotumumab is a fully human monoclonal antibody that selectively targets the lig and of the MET receptor , hepatocyte growth factor ( HGF ) . We aim ed to assess the efficacy , safety , and pharmacokinetics of rilotumumab combined with epirubicin , cisplatin , and capecitabine , and to assess potential biomarkers , in patients with advanced MET-positive gastric or gastro-oesophageal junction adenocarcinoma . METHODS This multicentre , r and omised , double-blind , placebo-controlled , phase 3 study was done at 152 centres in 27 countries . We recruited adults ( aged ≥18 years ) with unresectable locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma , an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 or 1 , MET-positive tumours ( ≥25 % of tumour cells with membrane staining of ≥1 + staining intensity ) , and evaluable disease , who had not received previous systemic therapy . Eligible patients were r and omly assigned ( 1:1 ) via a computerised voice response system to receive rilotumumab 15 mg/kg intravenously or placebo in combination with open-label chemotherapy ( epirubicin 50 mg/m2 intravenously ; cisplatin 60 mg/m2 intravenously ; capecitabine 625 mg/m2 orally twice daily ) in 21-day cycles for up to ten cycles . After completion of chemotherapy , patients continued to receive rilotumumab or placebo monotherapy until disease progression , intolerability , withdrawal of consent , or study termination . R and omisation was stratified by disease 
    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: BACKGROUND This r and omised study compared protracted venous infusion ( PVI ) fluorouracil ( 5-FU ) with PVI 5-FU plus mitomycin C ( MMC ) in patients with advanced oesophago-gastric cancer . PATIENTS AND METHODS Two hundred and fifty-four patients with adenocarcinoma , squamous cell carcinoma or undifferentiated carcinoma involving the oesophagus , oesophago-gastric junction or the stomach were r and omised . The major end points were tumour response , survival , toxicity and quality of life . RESULTS The median age of patients treated was 72 years and the two arms were well-balanced for baseline demographic factors . The overall response rate was 16.1 % [ 95 % confidence interval ( CI ) 9.5 % to 22.7 % ] in patients treated with PVI 5-FU alone compared with 19.1 % ( 95 % CI 12.0 % to 26.0 % ) for those treated with PVI 5-FU plus MMC ( P = 0.555 ) . Median time to treatment failure was 3.9 months for PVI 5-FU and 3.8 months for PVI 5-FU plus MMC ( P = 0.195 ) . Median survival was 6.3 months for PVI 5-FU and 5.3 months for PVI 5-FU plus MMC ( P = 1.0 ) . Toxicity was mild for both treatments . Symptomatic benefit measured by improvement in pain control , weight loss , dysphagia and oesophageal reflux was observed in over 64 % of patients in each arm . Quality of life scores were comparable in each arm . CONCLUSIONS PVI 5-FU is a safe , effective form of palliation for patients with advanced oesophago-gastric cancer although the addition of MMC adds little extra benefit We report the final results of a prospect ively r and omized study that compared the combination of epirubicin , cisplatin and protracted venous infusion fluorouracil ( 5-FU ) ( ECF regimen ) with the st and ard combination of 5-FU , doxorubicin and methotrexate ( FAMTX ) in previously untreated patients with advanced oesophagogastric cancer . Between 1992 and 1995 , 274 patients with adenocarcinoma or undifferentiated carcinoma were r and omized from eight oncology centres in the UK and analysed for response and survival . The overall response rate was 46 % ( 95 % confidence interval ( CI ) , 37–55 % ) with ECF , and 21 % ( 95 % CI , 13–28 % ) with FAMTX ( P = 0.00003 ) . The median survival was 8.7 months with ECF and 6.1 months with FAMTX ( P = 0.0005 ) . The 2-year survival rates were 14 % ( 95 % CI , 8–20 % ) for the ECF arm , and 5 % ( 95 % CI , 2–10 % ) for the FAMTX arm ( P = 0.03 ) . Histologically complete surgical resection following chemotherapy was achieved in ten patients in the ECF arm ( three pathological complete responses to chemotherapy ) and three patients in the FAMTX arm ( no pathological complete responses ) . The ECF regimen result ed in a response and survival advantage compared with FAMTX chemotherapy . The probability of long-term survival following surgical resection of residual disease is increased by this treatment . The high response rates seen with ECF support its use in the neoadjuvant setting Importance Dysregulation of the mesenchymal-epithelial transition ( MET ) signaling pathway is associated with poor prognosis in gastroesophageal adenocarcinoma ( GEC ) . We report results of METGastric , a phase 3 trial of the MET inhibitor onartuzumab plus st and ard first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative , MET-positive , advanced GEC . Objective To determine whether the addition of onartuzumab to first-line fluorouracil , leucovorin , and oxaliplatin ( mFOLFOX6 ) improves efficacy compared with mFOLFOX6 plus placebo in HER2-negative , MET-positive GEC . Design , Setting , and Participants R and omized , double-blind , multicenter trial conducted from November 2012 to March 2014 . Patients were 18 years or older with an adenocarcinoma of the stomach or gastroesophageal junction with metastatic disease not amenable for curative therapy . Tumor sample s were central ly tested for MET expression using Ventana anti-Total c-MET ( SP44 ) rabbit monoclonal antibody , HER2 status , and Lauren histologic subtype . MET-positive tumors were defined as at least 50 % of tumor cells showing weak , moderate , and /or strong staining intensity ( MET 1+/2+/3 + , respectively ) by immunohistochemistry . Interventions Patients with HER2-negative , MET-positive GEC were enrolled and r and omized 1:1 to receive mFOLFOX6 with or without onartuzumab ( 10 mg/kg ) . Main Outcomes and Measures Co– primary end points : overall survival in the intent-to-treat ( ITT ) population and in patients with MET 2+/3 + GEC . Secondary end points : progression-free survival ( PFS ) , overall response rate ( ORR ) , and safety . Results Enrollment was stopped early due to sponsor decision , which was agreed with an independent data monitoring committee . At the data cutoff ( April 25 , 2014 ) there were 562 patients in the ITT population ( n = 283 placebo plus mFOLFOX6 [ median age , 58 y ; 65 % male ] ; n = 279 onartuzumab plus mFOLFOX6 [ median age , 60 y ; 67 % male ] ) ; 109 ( 38.5 % ) and 105 ( 37.6 % ) of the ITT population were MET 2+/3 + , respectively . Addition of onartuzumab to mFOLFOX6 did not significantly improve OS , PFS , or ORR vs placebo plus mFOLFOX6 in the ITT ( OS hazard ratio [ HR ] , 0.82 ; 95 % CI , 0.59 - 1.15 ; P = .24 ; PFS HR , 0.90 ; 95 % CI , 0.71 - 1.16 ; P = .43 ; ORR , 46.1 % vs 40.6 % ) or MET 2+/3 + population s ( OS HR , 0.64 ; 95 % CI , 0.40 - 1.03 ; P = .06 ; PFS HR , 0.79 ; 95 % CI , 0.54 - 1.15 ; P = .22 ; ORR , 53.8 % vs 44.6 % ) . Safety was as expected for onartuzumab . Conclusions and Relevance Addition of onartuzumab to first-line mFOLFOX6 did not significantly improve clinical benefits in the ITT or MET 2+/3 + population s. Trial Registration clinical trials.gov Identifier : OBJECTIVES More than half of cases of gastric cancer ( GC ) are diagnosed in elderly patients ( ≥70years ) . While doublet combination with fluoropyrimidines and platinum is currently considered st and ard first-line chemotherapy in advanced GC , the main goal of chemotherapy remains palliation . MATERIAL S AND METHODS In a multi-center phase III trial , patients with chemotherapy-naïve , metastatic GC , aged 70years or older were r and omized 1:1 to receive X monotherapy ( capecitabine 1000mg/m2 bid po on days one to fourteen ) or XELOX ( X plus oxaliplatin 110mg/m2 iv on D1 ) . Treatment was repeated every 21days until disease progression , unacceptable toxicity , or withdrawal . Primary endpoint was overall survival ( OS ) . RESULTS In total , 50 patients with a median age of 77 ( range , 70 to 84 ) were enrolled ( X , n=26 ; XELOX , n=24 ) . No treatment-related serious adverse events or unexpected toxicities were observed . The most frequently observed toxicities were nausea and h and -foot syndrome , with fatigue and peripheral neuropathy more common in XELOX than in X patients . Median OS was 11.1months for XELOX arm and 6.3months for X arm ( HR 0.58 , 95 % CI 0.30 - 1.12 , P=0.108 ) . Although the difference was not significant , on the basis of evidence of superiority of XELOX seen in the first interim analysis , an independent data monitoring committee recommended early stopping of the trial . PFS was significantly longer ( HR 0.32 , 95 % CI 0.17 - 0.61 , P<0.001 ) with XELOX ( 7.1months ) than with X ( 2.6months ) . CONCLUSION Platinum-based combination chemotherapy was associated with survival benefit , as compared with X monotherapy in elderly patients with GC Background : Elderly patients are commonly under-represented in cancer clinical trials . The 321GO was undertaken in preparation for a definitive phase three trial assessing different chemotherapy regimens in a frail and /or elderly population with advanced gastroesophageal ( GO ) cancer . Methods : Patients with advanced GO cancer considered unfit for conventional dose chemotherapy were r and omly assigned in a 1 : 1 : 1 ratio to : epirubicin , oxaliplatin and capecitabine ( EOX ) ; oxaliplatin and capecitabine ( OX ) ; and capecitabine alone ( X ) ( all 80 % of full dose and unblinded ) . The primary end point was patient recruitment over an 18-month period . A registration study recorded treatment choice for all patients with advanced GO cancer at trial centres . Results : A total of 313 patients were considered for palliative chemotherapy for GO cancer over the 18-month period : 115 received full dose treatment , 89 less than st and ard treatment or entered 321GO and 111 no treatment . Within 321GO , 55 patients were r and omly assigned ( 19 to OX and X ; 17 to EOX ) . Progression-free survival ( PFS ) for all patients was 4.4 months and by arm 5.4 , 5.6 and 3.0 months for EOX , OX and X , respectively . The number of patients with a good overall treatment utility ( OTU ) , a novel patient-centred endpoint , at 12 weeks was 3 ( 18 % ) , 6 ( 32 % ) and 1 ( 6 % ) for EOX , OX and X , respectively . At 6 weeks , 22 patients ( 41 % ) had experienced a non-haematologic toxicity ⩾ grade 3 , most commonly lethargy or diarrhoea . The OTU was prognostic for overall survival in patients alive at week 12 ( logrank test P=0.0001 ) . Conclusions : It is feasible to recruit elderly and /or frail patients with advanced GO cancer to a r and omised clinical trial . The OX is the preferred regimen for further study . Overall treatment utility shows promise as a comparator between treatment regimens for feasibility and r and omised trials in the elderly and /or frail GO cancer population BACKGROUND Rilotumumab is a fully human monoclonal antibody that selectively targets the lig and of the MET receptor , hepatocyte growth factor ( HGF ) . We aim ed to assess the efficacy , safety , and pharmacokinetics of rilotumumab combined with epirubicin , cisplatin , and capecitabine , and to assess potential biomarkers , in patients with advanced MET-positive gastric or gastro-oesophageal junction adenocarcinoma . METHODS This multicentre , r and omised , double-blind , placebo-controlled , phase 3 study was done at 152 centres in 27 countries . We recruited adults ( aged ≥18 years ) with unresectable locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma , an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 or 1 , MET-positive tumours ( ≥25 % of tumour cells with membrane staining of ≥1 + staining intensity ) , and evaluable disease , who had not received previous systemic therapy . Eligible patients were r and omly assigned ( 1:1 ) via a computerised voice response system to receive rilotumumab 15 mg/kg intravenously or placebo in combination with open-label chemotherapy ( epirubicin 50 mg/m2 intravenously ; cisplatin 60 mg/m2 intravenously ; capecitabine 625 mg/m2 orally twice daily ) in 21-day cycles for up to ten cycles . After completion of chemotherapy , patients continued to receive rilotumumab or placebo monotherapy until disease progression , intolerability , withdrawal of consent , or study termination . R and omisation was stratified by disease 
    Output:
    