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 Several studies have shown the efficacy , tolerability , and ease of administration of pemetrexed-an antifolate antineoplastic agent-in  patients with advanced non-small-cell lung cancer . We assessed pemetrexed as maintenance therapy in patients with this disease . METHODS This r and omised double-blind study was undertaken in 83 centres in 20 countries . 663 patients with stage IIIB or IV disease who had not progressed on four cycles of platinum-based chemotherapy  were r and omly assigned ( 2:1 ratio ) to receive pemetrexed ( 500 mg/m(2 ) , day 1 ) plus best supportive care ( n=441 ) or placebo plus best supportive care ( n=222 ) in 21-day cycles until disease progression . Treatment was r and omised with the Simon and Pocock minimisation method . Patients and investigators were masked to treatment . All patients received vitamin B(12 ) , folic acid , and dexamethasone . The primary endpoint of progression-free survival and the secondary endpoint of overall survival were analysed by intention to treat . This study is registered with Clinical Trials.gov , number NCT00102804 . FINDINGS All r and omly assigned participants were analysed . Pemetrexed significantly improved progression-free survival ( 4.3 months [ 95 % CI 4.1 - 4.7 ] vs 2.6 months [ 1.7 - 2.8 ] ; hazard ratio [ HR ] 0.50 , 95 % CI 0.42 - 0.61 , p<0.0001 ) and overall survival ( 13.4 months [ 11.9 - 15.9 ] vs 10.6 months [ 8.7 - 12.0 ] ; HR 0.79 , 0.65 - 0.95 , p=0.012 ) compared with placebo . Treatment discontinuations due to drug-related toxic effects were higher in the pemetrexed group than in the placebo group ( 21 [ 5 % ] vs three [ 1 % ] ) . Drug-related grade three or higher toxic effects were higher with pemetrexed than with placebo ( 70 [ 16 % ] vs nine [ 4 % ] ; p<0.0001 ) , specifically fatigue ( 22 [ 5 % ] vs one [ 1 % ] , p=0.001 ) and neutropenia ( 13 [ 3 % ] vs 0 , p=0.006 ) . No  pemetrexed-related deaths occurred . Relatively fewer patients in the pemetrexed group than in the placebo group received systemic post-discontinuation therapy ( 227 [ 51 % ] vs 149 [ 67 % ] ; p=0.0001 ) . INTERPRETATION Maintenance therapy with pemetrexed is well tolerated and offers improved progression-free and overall survival compared with placebo in patients with advanced non-small-cell lung cancer . FUNDING Eli Lilly BACKGROUND Idiopathic pulmonary fibrosis is a fatal disease for which no effective treatment exists . We assessed whether treatment with interferon gamma-1b improved survival compared with placebo in patients with idiopathic pulmonary fibrosis and mild-to-moderate impairment of pulmonary function . METHODS 826 patients with idiopathic pulmonary fibrosis were enrolled from 81 centres in seven European countries , the USA , and Canada . Patients were r and omly assigned ( double-blind ) in a 2:1 ratio to receive 200 microg interferon gamma-1b ( n=551 ) or equivalent placebo ( n=275 ) subcutaneously , three times per week . Eligible patients were aged 40 - 79 years , had been diagnosed in the past 48 months , had a forced vital capacity of 55 - 90 % of the predicted value , and a haemoglobin-corrected carbon monoxide diffusing capacity of 35 - 90 % of the predicted value . The primary endpoint was overall survival time from r and omisation measured at the second interim analysis , when the proportion of deaths had reached 75 % of those expected by the study conclusion . This study is registered with Clinical Trials.gov , number NCT00075998 . FINDINGS At the second interim analysis , the hazard ratio for mortality in patients on interferon gamma-1b showed absence of minimum benefit compared with placebo ( 1.15 , 95 % CI 0.77 - 1.71 , p=0.497 ) , and indicated that the study should be stopped . After a median duration of 64 weeks ( IQR 41 - 84 ) on treatment , 80 ( 15 % ) patients on interferon gamma-1b and 35 ( 13 % ) on placebo had died . Almost all patients reported at least one adverse event , and more patients on interferon gamma-1b group had constitutional signs and symptoms ( influenza-like illness , fatigue , fever , and chills ) than did those on placebo . Occurrence of serious adverse events ( eg , pneumonia , respiratory failure ) was similar for both treatment groups . Treatment adherence was good and few patients discontinued treatment prematurely in either group . INTERPRETATION We can not recommend treatment with interferon gamma-1b since the drug did not improve survival for patients with idiopathic pulmonary fibrosis , which refutes previous findings from subgroup analyses of survival in studies of patients with mild-to-moderate physiological impairment of pulmonary function . FUNDING InterMune In a r and omised , controlled study alternate day prednisolone with an initial high dose phase ( " prednisolone only series " ) has been compared with cyclophosphamide plus alternate day low dose prednisolone ( " cyclophosphamide-prednisolone series " ) in 43 patients with previously untreated fibrosing alveolitis ( five patients had received prednisolone in minimal dosage ) . In the prednisolone only series prednisolone 60 mg daily was given for one month and then reduced by 5 mg a week to 20 mg on alternate days or the minimum dose to maintain early improvement . Patients in the cyclophosphamide-prednisolone series received 100 , 110 , or 120 mg cyclophosphamide daily ( depending on body weight ) plus 20 mg prednisolone on alternate days . Treatment was continued indefinitely , or changed to the alternative regimen if the patient deteriorated , failed to improve , or developed drug toxicity . For response to treatment ( as judged by change in breathlessness score , radiographic appearance , and lung function ) patients were classified as improved , stable , or deteriorating . Deaths from cryptogenic fibrosing alveolitis were also analysed . Improvement had occurred at one or more assessment s in seven of the 22 patients in the prednisolone only series and in five of the 21 patients in the cyclophosphamide-prednisolone series . At three years , however , only two of the 22 patients in the prednisolone only series were still improved and three stable , compared with one and seven of the 21 patients in the cyclophosphamide-prednisolone series ( three of the seven had stopped treatment because of toxicity ) . Life table analysis suggested better survival in patients in the cyclophosphamide-prednisolone series but this was not significant . At three years 10 of 22 patients in the prednisolone only series had died compared with three of 21 patients in the cyclophosphamide-prednisolone series . With death or failure of first treatment regimen as outcome there was a significant advantage to the patients having cyclophosphamide-prednisolone . This advantage was explained in part by the better lung volumes in this group on admission . After allowance had been made for total lung capacity ( TLC ) , no other factor was predictive of outcome . Analyses of subgroups according to TLC on admission showed that patients with a TLC below 60 % predicted did badly and those with a TLC of 80 % or more predicted did well with both regimens . Patients with an initial TLC of 60 - 79 % predicted did better with the cyclophosphamide-prednisolone regimen . Side effects were uncommon in both series and those due to cyclophosphamide resolved when treatment was stopped . The combination of cyclophosphamide with prednisolone may be an alternative to prednisolone alone with an initial high dose phase . Many patients , however , failed to respond to either treatment BACKGROUND Idiopathic pulmonary fibrosis is a progressive and fatal lung disease with inevitable loss of lung function . The CAPACITY programme ( studies 004 and 006 ) was design ed to confirm the results of a phase 2 study that suggested that pirfenidone , a novel antifibrotic and anti-inflammatory drug , reduces deterioration in lung function in patients with idiopathic pulmonary fibrosis . METHODS In two concurrent trials ( 004 and 006 ) , patients ( aged 40 - 80 years ) with idiopathic pulmonary fibrosis were r and omly assigned to oral pirfenidone or placebo for a minimum of 72 weeks in 110 centres in Australia , Europe , and North America . In study 004 , patients were assigned in a 2:1:2 ratio to pirfenidone 2403 mg/day , pirfenidone 1197 mg/day , or placebo ; in study 006 , patients were assigned in a 1:1 ratio to pirfenidone 2403 mg/day or placebo . The r and omisation code ( permuted block design ) was computer generated and stratified by region . All study personnel were masked to treatment group assignment until after final data base lock . Treatments were administered orally , 801 mg or 399 mg three times a day . The primary endpoint was change in percentage predicted forced vital capacity ( FVC ) at week 72 . Analysis was by intention to treat . The studies are registered with Clinical Trials.gov , numbers NCT00287729 and NCT00287716 . FINDINGS In study 004 , 174 of 435 patients were assigned to pirfenidone 2403 mg/day , 87 to pirfenidone 1197 mg/day , and 174 to placebo . In study 006 , 171 of 344 patients were assigned to pirfenidone 2403 mg/day , and 173 to placebo . All patients in both studies were analysed . In study 004 , pirfenidone reduced decline in FVC ( p=0·001 ) . Mean FVC change at week 72 was -8·0 % ( SD 16·5 ) in the pirfenidone 2403 mg/day group and -12·4 % ( 18·5 ) in the placebo group ( difference 4·4 % , 95 % CI 0·7 to 9·1 ) ; 35 ( 20 % ) of 174 versus 60 ( 35 % ) of 174 patients , respectively , had a decline of at least 10 % . A significant treatment effect was noted at all timepoints from week 24 and in an analysis over all study timepoints ( p=0·0007 ) . Mean change in percentage FVC in the pirfenidone 1197 mg/day group was intermediate to that in the pirfenidone 2403 mg/day and placebo groups . In study 006 , the difference between groups in FVC change at week 72 was not significant ( p=0·501 ) . Mean change in FVC at week 72 was -9·0 % ( SD 19·6 ) in the pirfenidone group and -9·6 % ( 19·1 ) in the placebo group , and the difference between groups in predicted FVC change at week 72 was not significant ( 0·6 % , -3·5 to 4·7 ) ; however , a consistent pirfenidone effect was apparent until week 48 ( p=0·005 ) and in an analysis of all study timepoints ( p=0·007 ) . Patients in the pirfenidone 2403 mg/day group had higher incidences of nausea ( 125 [ 36 % ] of 345 vs 60 [ 17 % ] of 347 ) , dyspepsia ( 66 [ 19 % ] vs 26 [ 7 % ] ) , vomiting ( 47 [ 14 % ] vs 15 [ 4 % ] ) , anorexia ( 37 [ 11 % ] vs 13 [ 4 % ] ) , photosensitivity ( 42 [ 12 % ] vs 6 [ 2 % ] ) , rash ( 111 [ 32 % ] vs 40 [ 12 % ] ) , and dizziness ( 63 [ 18 % ] vs 35 [ 10 % ] ) than did those in the placebo group . Fewer overall deaths ( 19 [ 6 % ] vs 29 [ 8 % ] ) and fewer deaths related to idiopathic pulmonary fibrosis ( 12 [ 3 % ] vs 25 [ 7 % ] ) occurred in the pirfenidone 2403 mg/day groups than in the placebo groups . INTERPRETATION The data show pirfenidone has a favourable benefit risk profile and represents an appropriate treatment option for patients with idiopathic pulmonary fibrosis . FUNDING InterMune BACKGROUND Idiopathic pulmonary fibrosis is a progressive , fatal disease with no known efficacious therapy . METHODS In a double-blind , multinational trial , we r and omly assigned 330 patients with idiopathic pulmonary fibrosis 
    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 Several studies have shown the efficacy , tolerability , and ease of administration of pemetrexed-an antifolate antineoplastic agent-in  patients with advanced non-small-cell lung cancer . We assessed pemetrexed as maintenance therapy in patients with this disease . METHODS This r and omised double-blind study was undertaken in 83 centres in 20 countries . 663 patients with stage IIIB or IV disease who had not progressed on four cycles of platinum-based chemotherapy  were r and omly assigned ( 2:1 ratio ) to receive pemetrexed ( 500 mg/m(2 ) , day 1 ) plus best supportive care ( n=441 ) or placebo plus best supportive care ( n=222 ) in 21-day cycles until disease progression . Treatment was r and omised with the Simon and Pocock minimisation method . Patients and investigators were masked to treatment . All patients received vitamin B(12 ) , folic acid , and dexamethasone . The primary endpoint of progression-free survival and the secondary endpoint of overall survival were analysed by intention to treat . This study is registered with Clinical Trials.gov , number NCT00102804 . FINDINGS All r and omly assigned participants were analysed . Pemetrexed significantly improved progression-free survival ( 4.3 months [ 95 % CI 4.1 - 4.7 ] vs 2.6 months [ 1.7 - 2.8 ] ; hazard ratio [ HR ] 0.50 , 95 % CI 0.42 - 0.61 , p<0.0001 ) and overall survival ( 13.4 months [ 11.9 - 15.9 ] vs 10.6 months [ 8.7 - 12.0 ] ; HR 0.79 , 0.65 - 0.95 , p=0.012 ) compared with placebo . Treatment discontinuations due to drug-related toxic effects were higher in the pemetrexed group than in the placebo group ( 21 [ 5 % ] vs three [ 1 % ] ) . Drug-related grade three or higher toxic effects were higher with pemetrexed than with placebo ( 70 [ 16 % ] vs nine [ 4 % ] ; p<0.0001 ) , specifically fatigue ( 22 [ 5 % ] vs one [ 1 % ] , p=0.001 ) and neutropenia ( 13 [ 3 % ] vs 0 , p=0.006 ) . No  pemetrexed-related deaths occurred . Relatively fewer patients in the pemetrexed group than in the placebo group received systemic post-discontinuation therapy ( 227 [ 51 % ] vs 149 [ 67 % ] ; p=0.0001 ) . INTERPRETATION Maintenance therapy with pemetrexed is well tolerated and offers improved progression-free and overall survival compared with placebo in patients with advanced non-small-cell lung cancer . FUNDING Eli Lilly BACKGROUND Idiopathic pulmonary fibrosis is a fatal disease for which no effective treatment exists . We assessed whether treatment with interferon gamma-1b improved survival compared with placebo in patients with idiopathic pulmonary fibrosis and mild-to-moderate impairment of pulmonary function . METHODS 826 patients with idiopathic pulmonary fibrosis were enrolled from 81 centres in seven European countries , the USA , and Canada . Patients were r and omly assigned ( double-blind ) in a 2:1 ratio to receive 200 microg interferon gamma-1b ( n=551 ) or equivalent placebo ( n=275 ) subcutaneously , three times per week . Eligible patients were aged 40 - 79 years , had been diagnosed in the past 48 months , had a forced vital capacity of 55 - 90 % of the predicted value , and a haemoglobin-corrected carbon monoxide diffusing capacity of 35 - 90 % of the predicted value . The primary endpoint was overall survival time from r and omisation measured at the second interim analysis , when the proportion of deaths had reached 75 % of those expected by the study conclusion . This study is registered with Clinical Trials.gov , number NCT00075998 . FINDINGS At the second interim analysis , the hazard ratio for mortality in patients on interferon gamma-1b showed absence of minimum benefit compared with placebo ( 1.15 , 95 % CI 0.77 - 1.71 , p=0.497 ) , and indicated that the study should be stopped . After a median duration of 64 weeks ( IQR 41 - 84 ) on treatment , 80 ( 15 % ) patients on interferon gamma-1b and 35 ( 13 % ) on placebo had died . Almost all patients reported at least one adverse event , and more patients on interferon gamma-1b group had constitutional signs and symptoms ( influenza-like illness , fatigue , fever , and chills ) than did those on placebo . Occurrence of serious adverse events ( eg , pneumonia , respiratory failure ) was similar for both treatment groups . Treatment adherence was good and few patients discontinued treatment prematurely in either group . INTERPRETATION We can not recommend treatment with interferon gamma-1b since the drug did not improve survival for patients with idiopathic pulmonary fibrosis , which refutes previous findings from subgroup analyses of survival in studies of patients with mild-to-moderate physiological impairment of pulmonary function . FUNDING InterMune In a r and omised , controlled study alternate day prednisolone with an initial high dose phase ( " prednisolone only series " ) has been compared with cyclophosphamide plus alternate day low dose prednisolone ( " cyclophosphamide-prednisolone series " ) in 43 patients with previously untreated fibrosing alveolitis ( five patients had received prednisolone in minimal dosage ) . In the prednisolone only series prednisolone 60 mg daily was given for one month and then reduced by 5 mg a week to 20 mg on alternate days or the minimum dose to maintain early improvement . Patients in the cyclophosphamide-prednisolone series received 100 , 110 , or 120 mg cyclophosphamide daily ( depending on body weight ) plus 20 mg prednisolone on alternate days . Treatment was continued indefinitely , or changed to the alternative regimen if the patient deteriorated , failed to improve , or developed drug toxicity . For response to treatment ( as judged by change in breathlessness score , radiographic appearance , and lung function ) patients were classified as improved , stable , or deteriorating . Deaths from cryptogenic fibrosing alveolitis were also analysed . Improvement had occurred at one or more assessment s in seven of the 22 patients in the prednisolone only series and in five of the 21 patients in the cyclophosphamide-prednisolone series . At three years , however , only two of the 22 patients in the prednisolone only series were still improved and three stable , compared with one and seven of the 21 patients in the cyclophosphamide-prednisolone series ( three of the seven had stopped treatment because of toxicity ) . Life table analysis suggested better survival in patients in the cyclophosphamide-prednisolone series but this was not significant . At three years 10 of 22 patients in the prednisolone only series had died compared with three of 21 patients in the cyclophosphamide-prednisolone series . With death or failure of first treatment regimen as outcome there was a significant advantage to the patients having cyclophosphamide-prednisolone . This advantage was explained in part by the better lung volumes in this group on admission . After allowance had been made for total lung capacity ( TLC ) , no other factor was predictive of outcome . Analyses of subgroups according to TLC on admission showed that patients with a TLC below 60 % predicted did badly and those with a TLC of 80 % or more predicted did well with both regimens . Patients with an initial TLC of 60 - 79 % predicted did better with the cyclophosphamide-prednisolone regimen . Side effects were uncommon in both series and those due to cyclophosphamide resolved when treatment was stopped . The combination of cyclophosphamide with prednisolone may be an alternative to prednisolone alone with an initial high dose phase . Many patients , however , failed to respond to either treatment BACKGROUND Idiopathic pulmonary fibrosis is a progressive and fatal lung disease with inevitable loss of lung function . The CAPACITY programme ( studies 004 and 006 ) was design ed to confirm the results of a phase 2 study that suggested that pirfenidone , a novel antifibrotic and anti-inflammatory drug , reduces deterioration in lung function in patients with idiopathic pulmonary fibrosis . METHODS In two concurrent trials ( 004 and 006 ) , patients ( aged 40 - 80 years ) with idiopathic pulmonary fibrosis were r and omly assigned to oral pirfenidone or placebo for a minimum of 72 weeks in 110 centres in Australia , Europe , and North America . In study 004 , patients were assigned in a 2:1:2 ratio to pirfenidone 2403 mg/day , pirfenidone 1197 mg/day , or placebo ; in study 006 , patients were assigned in a 1:1 ratio to pirfenidone 2403 mg/day or placebo . The r and omisation code ( permuted block design ) was computer generated and stratified by region . All study personnel were masked to treatment group assignment until after final data base lock . Treatments were administered orally , 801 mg or 399 mg three times a day . The primary endpoint was change in percentage predicted forced vital capacity ( FVC ) at week 72 . Analysis was by intention to treat . The studies are registered with Clinical Trials.gov , numbers NCT00287729 and NCT00287716 . FINDINGS In study 004 , 174 of 435 patients were assigned to pirfenidone 2403 mg/day , 87 to pirfenidone 1197 mg/day , and 174 to placebo . In study 006 , 171 of 344 patients were assigned to pirfenidone 2403 mg/day , and 173 to placebo . All patients in both studies were analysed . In study 004 , pirfenidone reduced decline in FVC ( p=0·001 ) . Mean FVC change at week 72 was -8·0 % ( SD 16·5 ) in the pirfenidone 2403 mg/day group and -12·4 % ( 18·5 ) in the placebo group ( difference 4·4 % , 95 % CI 0·7 to 9·1 ) ; 35 ( 20 % ) of 174 versus 60 ( 35 % ) of 174 patients , respectively , had a decline of at least 10 % . A significant treatment effect was noted at all timepoints from week 24 and in an analysis over all study timepoints ( p=0·0007 ) . Mean change in percentage FVC in the pirfenidone 1197 mg/day group was intermediate to that in the pirfenidone 2403 mg/day and placebo groups . In study 006 , the difference between groups in FVC change at week 72 was not significant ( p=0·501 ) . Mean change in FVC at week 72 was -9·0 % ( SD 19·6 ) in the pirfenidone group and -9·6 % ( 19·1 ) in the placebo group , and the difference between groups in predicted FVC change at week 72 was not significant ( 0·6 % , -3·5 to 4·7 ) ; however , a consistent pirfenidone effect was apparent until week 48 ( p=0·005 ) and in an analysis of all study timepoints ( p=0·007 ) . Patients in the pirfenidone 2403 mg/day group had higher incidences of nausea ( 125 [ 36 % ] of 345 vs 60 [ 17 % ] of 347 ) , dyspepsia ( 66 [ 19 % ] vs 26 [ 7 % ] ) , vomiting ( 47 [ 14 % ] vs 15 [ 4 % ] ) , anorexia ( 37 [ 11 % ] vs 13 [ 4 % ] ) , photosensitivity ( 42 [ 12 % ] vs 6 [ 2 % ] ) , rash ( 111 [ 32 % ] vs 40 [ 12 % ] ) , and dizziness ( 63 [ 18 % ] vs 35 [ 10 % ] ) than did those in the placebo group . Fewer overall deaths ( 19 [ 6 % ] vs 29 [ 8 % ] ) and fewer deaths related to idiopathic pulmonary fibrosis ( 12 [ 3 % ] vs 25 [ 7 % ] ) occurred in the pirfenidone 2403 mg/day groups than in the placebo groups . INTERPRETATION The data show pirfenidone has a favourable benefit risk profile and represents an appropriate treatment option for patients with idiopathic pulmonary fibrosis . FUNDING InterMune BACKGROUND Idiopathic pulmonary fibrosis is a progressive , fatal disease with no known efficacious therapy . METHODS In a double-blind , multinational trial , we r and omly assigned 330 patients with idiopathic pulmonary fibrosis 
    Output:
    