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 The study compared the efficacy of a first-line treatment with day 1 i.v . vinorelbine ( NVBiv ) and day 8 oral vinorelbine ( NVBo ) versus docetaxel ( DCT ) in a cisplatin-based combination in advanced non-small-cell lung cancer , in terms of time to treatment failure ( TTF ) , overall response , progression-free survival ( PFS ) , overall survival ( OS ) , tolerance and quality of life ( QoL ) . METHODS Patients were r and omly assigned to receive cisplatin 80 mg/m2 with NVBiv 30 mg/m2 on day 1 and NVBo 80 mg/m2 on day 8 every 3 weeks , after a first cycle of NVBiv 25 mg/m2 on day 1 and NVBo 60 mg/m2 on day 8 ( arm A ) or cisplatin 75 mg/m2 and DCT 75 mg/m2 on day 1 every 3 weeks ( arm B ) , for a maximum of six cycles in both arms . RESULTS From 2 February 2004 to 1 January 2006 , 390 patients were entered in a r and omised study and 381 were treated . The patient characteristics are as follows ( arms A/B ) : metastatic ( % ) 80.5/84.8 ; patients with three or more organs involved  ( % ) 45.3/40.8 ; median age 59.4/62.1 years ; male 139/146 ; squamous ( % ) 34.2/33.5 ; adenocarcinoma ( % ) 41.6/39.3 ; median TTF ( arms A/B in months ) [ 95 % confidence interval ( CI ) ] : 3.2 ( 3.0 - 4.2 ) , 4.1 ( 3.4 - 4.5 ) ( P = 0.19 ) ; overall response ( arms A/B ) ( 95 % CI ) : 27.4 % ( 21.2 % to 34.2 % ) , 27.2 % ( 21.0 % to 34.2 % ) ; median PFS ( arms A/B in months ) ( 95 % CI ) : 4.9 ( 4.4 - 5.9 ) , 5.1 ( 4.3 - 6.1 ) ( P = 0.99 ) and median OS ( arms A/B in months ) ( 95 % CI ) : 9.9 ( 8.4 - 11.6 ) , 9.8 ( 8.8 - 11.5 ) ( P = 0.58 ) . The median survival for squamous histology was 8.87/9.82 months and for adenocarcinoma 11.73/11.60 months for arms A and B , respectively . Main haematological toxicity was grade 3 - 4 neutropenia : 24.4 % ( arm A ) and 28.8 % ( arm B ) . QoL as measured by the Lung Cancer Symptom Scale was similar in both arms . CONCLUSIONS Both arms provided similar efficacy in terms of response , time-related parameters and QoL , with an acceptable tolerance profile . In the current Global Lung Oncology Branch trial 3 , NVBo was shown to be effective as a substitute for the i.v . formulation . This can relieve the burden of the i.v . injection on day 8 and can optimise the hospital 's re sources and improve patient convenience BACKGROUND Necitumumab is a second-generation , recombinant , human immunoglobulin G1 EGFR antibody . In this study , we aim ed to compare treatment with necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone in patients with previously untreated stage IV squamous non-small-cell lung cancer . METHODS We did this open-label , r and omised phase 3 study at 184 investigative sites in 26 countries . Patients aged 18 years or older with histologically or cytologically confirmed stage IV squamous non-small-cell lung cancer , with an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 - 2 and adequate organ function and who had not received previous chemotherapy for their disease were eligible for inclusion . Enrolled patients were r and omly assigned central ly 1:1 to a maximum of six 3-week cycles of gemcitabine and cisplastin chemotherapy with or without necitumumab according to a block r and omisation scheme ( block size of four ) by a telephone-based interactive voice response system or interactive web response system . Chemotherapy was gemcitabine 1250 mg/m(2 ) administered intravenously over 30 min on days 1 and 8 of a 3-week cycle and cisplatin 75 mg/m(2 ) administered intravenously over 120 min on day 1 of a 3-week cycle . Necitumumab 800 mg , administered intravenously over a minimum of 50 min on days 1 and 8 , was continued after the end of chemotherapy until  disease progression or intolerable toxic side-effects occurred . R and omisation was stratified by ECOG performance status and geographical region . Neither physicians nor patients were masked to group assignment because of the expected occurrence of acne-like rash -- a class effect of EGFR antibodies -- that would have unmasked most patients and investigators to treatment . The primary endpoint was overall survival , analysed by intention to treat . We report the final clinical analysis . This study is registered with Clinical Trials.gov , number NCT00981058 . FINDINGS Between Jan 7 , 2010 , and Feb 22 , 2012 , we enrolled 1093 patients and r and omly assigned them to receive necitumumab plus gemcitabine and cisplatin ( n=545 ) or gemcitabine and cisplatin ( n=548 ) . Overall survival was significantly longer in the necitumumab plus gemcitabine and cisplatin group than in the gemcitabine and cisplatin alone group ( median 11·5 months [ 95 % CI 10·4 - 12·6 ] ) vs 9·9 months [ 8·9 - 11·1 ] ; stratified hazard ratio 0·84 [ 95 % CI 0·74 - 0·96 ; p=0·01 ] ) . In the necitumumab plus gemcitabine and cisplatin group , the number of patients with at least one grade 3 or worse adverse event was higher ( 388 [ 72 % ] of 538 patients ) than in the gemcitabine and cisplatin group ( 333 [ 62 % ] of 541 ) , as was the incidence of serious adverse events ( 257 [ 48 % ] of 538 patients vs 203 [ 38 % ] of 541 ) . More patients in the necitumumab plus gemcitabine and cisplatin group had grade 3 - 4 hypomagnesaemia ( 47 [ 9 % ] of 538 patients in the necitumumab plus gemcitabine and cisplatin group vs six [ 1 % ] of 541 in the gemcitabine and cisplatin group ) and grade 3 rash ( 20 [ 4 % ] vs one [ < 1 % ] ) . Including events related to disease progression , adverse events with an outcome of death were reported for 66 ( 12 % ) of 538 patients in the necitumumab plus gemcitabine and cisplatin group and 57 ( 11 % ) of 541 patients in the gemcitabine and cisplatin group ; these were deemed to be related to study drugs in 15 ( 3 % ) and ten ( 2 % ) patients , respectively . Overall , we found that the safety profile of necitumumab plus gemcitabine and cisplatin was acceptable and in line with expectations . INTERPRETATION Our findings show that the addition of necitumumab to gemcitabine and cisplatin chemotherapy improves overall survival in patients with advanced squamous non-small-cell lung cancer and represents a new first-line treatment option for this disease . FUNDING Eli Lilly and Company INTRODUCTION We conducted this analysis to determine whether survival of advanced NSCLC patients treated with platin-based chemotherapy doublets involving paclitaxel , docetaxel or gemcitabine was dependent on histological subtypes and treatment regimen . METHODS We retrospectively analyzed data from E1594 , a front-line phase III study in which advanced NSCLC patients were r and omized to receive one of four regimens : cisplatin-paclitaxel , cisplatin-gemcitabine , cisplatin-docetaxel , and carboplatin-paclitaxel . Patients were classified into four histology groups : squamous cell ( SCC ) , adeno- ( AC ) , large cell ( LCC ) and others including not otherwise specified ( O/NOS ) carcinoma . Logrank test was performed to compare overall survival ( OS ) and progression free survival ( PFS ) distributions according to histology as well as treatment . RESULTS Of 1139 patients including 716 men and 423 women , AC was the most common subtype ( 56.8 % ) , followed by SCC ( 19.7 % ) , O/NOS ( 17.0 % ) and LCC ( 6.5 % ) . Men were more likely to have SCC and women were more likely to have AC ( p = 0.002 ) . Among the four histology groups , there was no imbalance in regard to race , performance status , weight loss , brain metastasis or treatment . In each histology group , we found no significant difference in OS and PFS between the four chemotherapy regimens . Conversely , in each treatment arm , the survival outcome was similar between the four histology subtypes . CONCLUSIONS Our analysis suggests that histology does not predict survival benefit in advanced NSCLC patients treated with first-line platin-based doublets involving paclitaxel , docetaxel or gemcitabine Objective : Gemcitabine in low dose in prolonged infusion is a treatment with documented activity against a variety of tumors . We here report the first r and omized trial to compare st and ard brief and low-dose prolonged infusion of gemcitabine . Patients and Methods : Eligible patients had non-small cell lung cancer in stage IIIB ( wet ) or IV , Karnofsky performance status 100 to 70 ( Eastern Cooperative Oncology Group 0–2 ) , measurable disease , were chemonaïve and fulfilled the st and ard criteria for chemotherapy . In arm A ( st and ard treatment ) , gemcitabine was given at 1250 mg/m2 in 20 to 30 minutes and in arm B ( prolonged infusion ) at 250 mg/m2 in 6 hours infusion . All patients received gemcitabine on days 1 and 8 and cisplatin at 75 mg/m2 on day 2 of a 3-week cycle for four cycles , followed by two cycles of gemcitabine as monotherapy . Results : A total of 249 patients ( 188 men and 61 women , median age 58 years ) were r and omized between arm A ( 125 patients ) and arm B ( 124 patients ) . Adenocarcinoma ( 53.9 % ) was the predominant histologic type ; 92 % of patients were in stage IV . The two groups were balanced for prognostic factors ; however , group A had fewer patients with significant weight loss and no patient with lung cancer as a second malignancy or after radiotherapy for brain metastases . Grade 3 or greater toxicity was rare : anemia in 0.8 and 3.2 % , neutropenia in 21.6 and 22.6 % , thrombocytopenia in 0 and 1.6 % , and nausea/vomiting in 4 and 8.1 % for arms A and B , respectively . Alopecia was seen in 54.5 % of patients in arm B , as compared with 9.7 % in arm A. No patient died of treatment-related toxicity . During cycle 5 , 47.7 % of patients in arm A and 60.7 % in arm B reported improved well-being , as compared with the status before chemotherapy . Patients in arm A had no complete remission , 32.8 % partial responses , 48 % minimal responses or stable disease , 13.6 % progressions , and 5.6 % were not evaluable . For arm B , the corresponding figures are as follows : complete remission 0.8 % , partial responses 46 % ( for overall response rate of 46.8 % ) , minimal responses or stable disease 36.3 % , progression 12.1 % , and not evaluable 4.8 % . Median progression-free survival was 5.5 and 6.0 months , median overall survival was 10.1 and 10.0 months , and 1-year survival was 46.6 and 41.1 % for arms A and B , respectively . For the 71 patients with squamous carcinoma , arm B seems superior to arm A , as seen by the higher overall response rate ( 51.3 versus 35.5 % ) , longer median progression-free survival ( 6.2 versus 4.9 months ) , and longer median survival ( 11.3 versus 8.5 months ) . However , because of the small number of patients , these differences did not reach the level of statistical significance . Conclusion : In the treatment of advanced non-small cell lung cancer , gemcitabine in low dose in prolonged infusion in combination with cisplatin has low toxicity and has activity comparable with gemcitabine in higher dose in st and ard brief infusion . Low-dose gemcitabine may 
    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 The study compared the efficacy of a first-line treatment with day 1 i.v . vinorelbine ( NVBiv ) and day 8 oral vinorelbine ( NVBo ) versus docetaxel ( DCT ) in a cisplatin-based combination in advanced non-small-cell lung cancer , in terms of time to treatment failure ( TTF ) , overall response , progression-free survival ( PFS ) , overall survival ( OS ) , tolerance and quality of life ( QoL ) . METHODS Patients were r and omly assigned to receive cisplatin 80 mg/m2 with NVBiv 30 mg/m2 on day 1 and NVBo 80 mg/m2 on day 8 every 3 weeks , after a first cycle of NVBiv 25 mg/m2 on day 1 and NVBo 60 mg/m2 on day 8 ( arm A ) or cisplatin 75 mg/m2 and DCT 75 mg/m2 on day 1 every 3 weeks ( arm B ) , for a maximum of six cycles in both arms . RESULTS From 2 February 2004 to 1 January 2006 , 390 patients were entered in a r and omised study and 381 were treated . The patient characteristics are as follows ( arms A/B ) : metastatic ( % ) 80.5/84.8 ; patients with three or more organs involved  ( % ) 45.3/40.8 ; median age 59.4/62.1 years ; male 139/146 ; squamous ( % ) 34.2/33.5 ; adenocarcinoma ( % ) 41.6/39.3 ; median TTF ( arms A/B in months ) [ 95 % confidence interval ( CI ) ] : 3.2 ( 3.0 - 4.2 ) , 4.1 ( 3.4 - 4.5 ) ( P = 0.19 ) ; overall response ( arms A/B ) ( 95 % CI ) : 27.4 % ( 21.2 % to 34.2 % ) , 27.2 % ( 21.0 % to 34.2 % ) ; median PFS ( arms A/B in months ) ( 95 % CI ) : 4.9 ( 4.4 - 5.9 ) , 5.1 ( 4.3 - 6.1 ) ( P = 0.99 ) and median OS ( arms A/B in months ) ( 95 % CI ) : 9.9 ( 8.4 - 11.6 ) , 9.8 ( 8.8 - 11.5 ) ( P = 0.58 ) . The median survival for squamous histology was 8.87/9.82 months and for adenocarcinoma 11.73/11.60 months for arms A and B , respectively . Main haematological toxicity was grade 3 - 4 neutropenia : 24.4 % ( arm A ) and 28.8 % ( arm B ) . QoL as measured by the Lung Cancer Symptom Scale was similar in both arms . CONCLUSIONS Both arms provided similar efficacy in terms of response , time-related parameters and QoL , with an acceptable tolerance profile . In the current Global Lung Oncology Branch trial 3 , NVBo was shown to be effective as a substitute for the i.v . formulation . This can relieve the burden of the i.v . injection on day 8 and can optimise the hospital 's re sources and improve patient convenience BACKGROUND Necitumumab is a second-generation , recombinant , human immunoglobulin G1 EGFR antibody . In this study , we aim ed to compare treatment with necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone in patients with previously untreated stage IV squamous non-small-cell lung cancer . METHODS We did this open-label , r and omised phase 3 study at 184 investigative sites in 26 countries . Patients aged 18 years or older with histologically or cytologically confirmed stage IV squamous non-small-cell lung cancer , with an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 - 2 and adequate organ function and who had not received previous chemotherapy for their disease were eligible for inclusion . Enrolled patients were r and omly assigned central ly 1:1 to a maximum of six 3-week cycles of gemcitabine and cisplastin chemotherapy with or without necitumumab according to a block r and omisation scheme ( block size of four ) by a telephone-based interactive voice response system or interactive web response system . Chemotherapy was gemcitabine 1250 mg/m(2 ) administered intravenously over 30 min on days 1 and 8 of a 3-week cycle and cisplatin 75 mg/m(2 ) administered intravenously over 120 min on day 1 of a 3-week cycle . Necitumumab 800 mg , administered intravenously over a minimum of 50 min on days 1 and 8 , was continued after the end of chemotherapy until  disease progression or intolerable toxic side-effects occurred . R and omisation was stratified by ECOG performance status and geographical region . Neither physicians nor patients were masked to group assignment because of the expected occurrence of acne-like rash -- a class effect of EGFR antibodies -- that would have unmasked most patients and investigators to treatment . The primary endpoint was overall survival , analysed by intention to treat . We report the final clinical analysis . This study is registered with Clinical Trials.gov , number NCT00981058 . FINDINGS Between Jan 7 , 2010 , and Feb 22 , 2012 , we enrolled 1093 patients and r and omly assigned them to receive necitumumab plus gemcitabine and cisplatin ( n=545 ) or gemcitabine and cisplatin ( n=548 ) . Overall survival was significantly longer in the necitumumab plus gemcitabine and cisplatin group than in the gemcitabine and cisplatin alone group ( median 11·5 months [ 95 % CI 10·4 - 12·6 ] ) vs 9·9 months [ 8·9 - 11·1 ] ; stratified hazard ratio 0·84 [ 95 % CI 0·74 - 0·96 ; p=0·01 ] ) . In the necitumumab plus gemcitabine and cisplatin group , the number of patients with at least one grade 3 or worse adverse event was higher ( 388 [ 72 % ] of 538 patients ) than in the gemcitabine and cisplatin group ( 333 [ 62 % ] of 541 ) , as was the incidence of serious adverse events ( 257 [ 48 % ] of 538 patients vs 203 [ 38 % ] of 541 ) . More patients in the necitumumab plus gemcitabine and cisplatin group had grade 3 - 4 hypomagnesaemia ( 47 [ 9 % ] of 538 patients in the necitumumab plus gemcitabine and cisplatin group vs six [ 1 % ] of 541 in the gemcitabine and cisplatin group ) and grade 3 rash ( 20 [ 4 % ] vs one [ < 1 % ] ) . Including events related to disease progression , adverse events with an outcome of death were reported for 66 ( 12 % ) of 538 patients in the necitumumab plus gemcitabine and cisplatin group and 57 ( 11 % ) of 541 patients in the gemcitabine and cisplatin group ; these were deemed to be related to study drugs in 15 ( 3 % ) and ten ( 2 % ) patients , respectively . Overall , we found that the safety profile of necitumumab plus gemcitabine and cisplatin was acceptable and in line with expectations . INTERPRETATION Our findings show that the addition of necitumumab to gemcitabine and cisplatin chemotherapy improves overall survival in patients with advanced squamous non-small-cell lung cancer and represents a new first-line treatment option for this disease . FUNDING Eli Lilly and Company INTRODUCTION We conducted this analysis to determine whether survival of advanced NSCLC patients treated with platin-based chemotherapy doublets involving paclitaxel , docetaxel or gemcitabine was dependent on histological subtypes and treatment regimen . METHODS We retrospectively analyzed data from E1594 , a front-line phase III study in which advanced NSCLC patients were r and omized to receive one of four regimens : cisplatin-paclitaxel , cisplatin-gemcitabine , cisplatin-docetaxel , and carboplatin-paclitaxel . Patients were classified into four histology groups : squamous cell ( SCC ) , adeno- ( AC ) , large cell ( LCC ) and others including not otherwise specified ( O/NOS ) carcinoma . Logrank test was performed to compare overall survival ( OS ) and progression free survival ( PFS ) distributions according to histology as well as treatment . RESULTS Of 1139 patients including 716 men and 423 women , AC was the most common subtype ( 56.8 % ) , followed by SCC ( 19.7 % ) , O/NOS ( 17.0 % ) and LCC ( 6.5 % ) . Men were more likely to have SCC and women were more likely to have AC ( p = 0.002 ) . Among the four histology groups , there was no imbalance in regard to race , performance status , weight loss , brain metastasis or treatment . In each histology group , we found no significant difference in OS and PFS between the four chemotherapy regimens . Conversely , in each treatment arm , the survival outcome was similar between the four histology subtypes . CONCLUSIONS Our analysis suggests that histology does not predict survival benefit in advanced NSCLC patients treated with first-line platin-based doublets involving paclitaxel , docetaxel or gemcitabine Objective : Gemcitabine in low dose in prolonged infusion is a treatment with documented activity against a variety of tumors . We here report the first r and omized trial to compare st and ard brief and low-dose prolonged infusion of gemcitabine . Patients and Methods : Eligible patients had non-small cell lung cancer in stage IIIB ( wet ) or IV , Karnofsky performance status 100 to 70 ( Eastern Cooperative Oncology Group 0–2 ) , measurable disease , were chemonaïve and fulfilled the st and ard criteria for chemotherapy . In arm A ( st and ard treatment ) , gemcitabine was given at 1250 mg/m2 in 20 to 30 minutes and in arm B ( prolonged infusion ) at 250 mg/m2 in 6 hours infusion . All patients received gemcitabine on days 1 and 8 and cisplatin at 75 mg/m2 on day 2 of a 3-week cycle for four cycles , followed by two cycles of gemcitabine as monotherapy . Results : A total of 249 patients ( 188 men and 61 women , median age 58 years ) were r and omized between arm A ( 125 patients ) and arm B ( 124 patients ) . Adenocarcinoma ( 53.9 % ) was the predominant histologic type ; 92 % of patients were in stage IV . The two groups were balanced for prognostic factors ; however , group A had fewer patients with significant weight loss and no patient with lung cancer as a second malignancy or after radiotherapy for brain metastases . Grade 3 or greater toxicity was rare : anemia in 0.8 and 3.2 % , neutropenia in 21.6 and 22.6 % , thrombocytopenia in 0 and 1.6 % , and nausea/vomiting in 4 and 8.1 % for arms A and B , respectively . Alopecia was seen in 54.5 % of patients in arm B , as compared with 9.7 % in arm A. No patient died of treatment-related toxicity . During cycle 5 , 47.7 % of patients in arm A and 60.7 % in arm B reported improved well-being , as compared with the status before chemotherapy . Patients in arm A had no complete remission , 32.8 % partial responses , 48 % minimal responses or stable disease , 13.6 % progressions , and 5.6 % were not evaluable . For arm B , the corresponding figures are as follows : complete remission 0.8 % , partial responses 46 % ( for overall response rate of 46.8 % ) , minimal responses or stable disease 36.3 % , progression 12.1 % , and not evaluable 4.8 % . Median progression-free survival was 5.5 and 6.0 months , median overall survival was 10.1 and 10.0 months , and 1-year survival was 46.6 and 41.1 % for arms A and B , respectively . For the 71 patients with squamous carcinoma , arm B seems superior to arm A , as seen by the higher overall response rate ( 51.3 versus 35.5 % ) , longer median progression-free survival ( 6.2 versus 4.9 months ) , and longer median survival ( 11.3 versus 8.5 months ) . However , because of the small number of patients , these differences did not reach the level of statistical significance . Conclusion : In the treatment of advanced non-small cell lung cancer , gemcitabine in low dose in prolonged infusion in combination with cisplatin has low toxicity and has activity comparable with gemcitabine in higher dose in st and ard brief infusion . Low-dose gemcitabine may 
    Output:
    