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: Response rate and toxicity of second-line therapy with docetaxel ( 75 mg m−2 ) or docetaxel , irinotecan , and lenogastrim ( 60 mg m−2 , 200 mg m−2 , and 150 μg m−2 day−1 , respectively ) were compared in 108 patients with stage IIIb – IV non-small-cell lung cancer . Addition of irinotecan to docetaxel does not improve response rate , and increases gastrointestinal toxicity 7034 Background : D is now the st and ard second-line treatment for NSCLC patients based upon improved survival and quality of life in two phase III studies . DG has been also promising in several phase II trials in second-line setting . In order to evaluate whether combination regimen of DG provides better overall survival than D in patients with previously treated NSCLC , we conducted a r and omized trial . METHODS Eligibility included pathologically or cytologically proven NSCLC , stage IV or IIIB , one prior platinum-based regimen chemotherapy , performance status 0 or 1 , 20 - 75 years old . Patients were r and omized to receive either D ( 60 mg/m2 , day 1 ) or DG ( D 60 mg/m2 , day 8 , G 800 mg/m2 , days 1 , 8) , repeated every 21 days until disease progression . RESULTS 65 patients were accrued in each arm between Jan. 2002 and Apr. 2003 ( planned ; 142 per arm ) ; one was ineligible due to stage IIIA . This trial was terminated early with unexpected high incidence of interstitial lung disease ( ILD ) and 3 treatment related death ( 5 % ) due to ILD only in DG arm , which were identified by Adverse Event Reporting system . DG compared with D patients experienced similar grade 3 - 4 neutropenia ( DG 70 % , D 75 % ) , grade 2 - 4 nausea ( 17 % , 15 % ) , anorexia ( 20 % , 23 % ) , constipation ( 21 % , 30 % ) , alopecia ( 23 % , 24 % ) , febrile neutropenia ( 15 % , 25 % ) , but more dyspnea ( 23 % , 14 % ) and ILD ( 21 % , 2 % ) . There was no baseline factor identified for predicting ILD . The hazard ratio ( HR ) for overall survival was 0.89 ( 95 % CI 0.52 , 1.55 , logrank p = 0.69 ) in favor of DG . Median survival was 11.3 ( DG ) and 10.1 months ( D ) . One-year survival rate was 47 % and 38 % . The HR for progression free survival ( PFS ) was 0.68 ( 95 % CI 0.46 , 0.99 , p = 0.04 ) . Median PFS was 3.1 ( DG ) and 2.1 ( D ) months . CONCLUSIONS The combination of D and G may be too toxic regimen due to high risk of ILD for previously treated patients . D alone is still considered to be the st and ard second-line treatment for NSCLC . No significant financial relationships to disclose BACKGROUND We conducted a r and omized , placebo-controlled , double-blind trial to determine whether the epidermal growth factor receptor inhibitor erlotinib prolongs survival in non-small-cell lung cancer after the failure of first-line or second-line chemotherapy . METHODS Patients with stage IIIB or IV non-small-cell lung cancer , with performance status from 0 to 3 , were eligible if they had received one or two prior chemotherapy regimens .  The patients were stratified according to center , performance status , response to prior chemotherapy , number of prior regimens , and prior platinum-based therapy and were r and omly assigned in a 2:1 ratio to receive oral erlotinib , at a dose of 150 mg daily , or placebo . RESULTS The median age of the 731 patients who underwent r and omization was 61.4 years ; 49 percent had received two prior chemotherapy regimens , and 93 percent had received platinum-based chemotherapy .  The response rate was 8.9 percent in the erlotinib group and less than 1 percent in the placebo group ( P<0.001 ) ; the median duration of the response was 7.9 months and 3.7 months , respectively . Progression-free survival was 2.2 months and 1.8 months , respectively ( hazard ratio , 0.61 , adjusted for stratification categories ; P<0.001 ) . Overall survival was 6.7 months and 4.7 months , respectively ( hazard ratio , 0.70 ; P<0.001 ) , in favor of erlotinib . Five percent of patients discontinued erlotinib because of toxic effects . CONCLUSIONS Erlotinib can prolong survival in patients with non-small-cell lung cancer after first-line or second-line chemotherapy PURPOSE To evaluate the efficacy and tolerability of two doses of gefitinib ( Iressa [ ZD1839 ] ; AstraZeneca , Wilmington , DE ) , a novel epidermal growth factor receptor tyrosine kinase inhibitor , in patients with pretreated advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS This was a r and omized , double-blind , parallel-group , multicenter phase II trial . Two hundred ten patients with advanced NSCLC who were previously treated with one or two chemotherapy regimens ( at least one containing platinum )  were r and omly assigned to receive either 250-mg or 500-mg oral doses of gefitinib once daily . RESULTS Efficacy was similar for the 250- and 500-mg/d groups . Objective tumor response rates were 18.4 % ( 95 % confidence interval [ CI ] , 11.5 to 27.3 ) and 19.0 % ( 95 % CI , 12.1 to 27.9 ) ; among evaluable patients , symptom improvement rates were 40.3 % ( 95 % CI , 28.5 to 53.0 ) and 37.0 % ( 95 % CI , 26.0 to 49.1 ) ; median progression-free survival times were 2.7 and 2.8 months ; and median overall survival times were 7.6 and 8.0 months , respectively . Symptom improvements were recorded for 69.2 % ( 250 mg/d ) and 85.7 % ( 500 mg/d ) of patients with a tumor response . Adverse events ( AEs ) at both dose levels were generally mild ( grade 1 or 2 ) and consisted mainly of skin reactions and diarrhea . Drug-related toxicities were more frequent in the higher-dose group . Withdrawal due to drug-related AEs was 1.9 % and 9.4 % for patients receiving gefitinib 250 and 500 mg/d , respectively . CONCLUSION Gefitinib showed clinical ly meaningful antitumor activity and provided symptom relief as second- and third-line treatment in these patients . At 250 mg/d , gefitinib had a favorable AE profile . Gefitinib 250 mg/d is an important , novel treatment option for patients with pretreated advanced NSCLC [ corrected PURPOSE To confirm the promising phase II results of docetaxel monotherapy , this phase III trial was conducted of chemotherapy for patients with advanced non-small-cell lung cancer ( NSCLC ) who had previously failed platinum-containing chemotherapy . PATIENTS AND METHODS A total of 373 patients were r and omized to receive either docetaxel 100 mg/m(2 ) ( D100 ) or 75 mg/m(2 ) ( D75 ) versus a control regimen of vinorelbine or ifosfamide ( V/I ) . The three treatment groups were well-balanced for key patient characteristics . RESULTS Overall response rates were 10.8 % with D100 and 6.7 % with D75 , each significantly higher than the 0.8 % response with V/I ( P = .001 and P = .036 , respectively ) . Patients who received docetaxel had a longer time to progression ( P = .046 , by log-rank test ) and a greater progression-free survival at 26 weeks ( P = .005 , by chi(2 ) test ) . Although overall survival was not significantly different between the three groups , the 1-year survival was significantly greater with D75 than with the control treatment ( 32 % v 19 % ; P = .025 , by chi(2 ) test ) . Prior exposure to paclitaxel did not decrease the likelihood of response to docetaxel , nor did it impact survival . There was a trend toward greater efficacy in patients whose disease was platinum-resistant rather than platinum-refractory and in patients with performance status of 0 or 1 versus 2 . Toxicity was greatest with D100 , but the D75 arm was well-tolerated . CONCLUSION This first r and omized trial in this setting demonstrates that D75 every 3 weeks can offer clinical ly meaningful benefit to patients with advanced NSCLC whose disease has relapsed or progressed after platinum-based chemotherapy PURPOSE To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non-small-cell lung cancer who had previously been treated with platinum-based chemotherapy .  Secondary end points included assessment of response ( docetaxel arm only ) , toxicity , and quality of life . PATIENTS AND METHODS Patients with performance statuses of 0 to 2 and stage IIIB/IV non-small-cell lung cancer with either measurable or evaluable lesions were eligible for entry onto the study if they had undergone one or more platinum-based chemotherapy regimens and if they had adequate hematology and biochemistry parameters . They were excluded if they had symptomatic brain metastases or if they had previously been treated with paclitaxel .  Patients were stratified by performance status and best response to cisplatin chemotherapy and were then r and omized to treatment with docetaxel 100 mg/m(2 ) ( 49 patients ) or 75 mg/m(2 ) ( 55 patients ) or best supportive care . Patients in both arms were assessed every 3 weeks . RESULTS One hundred four patients ( 103 of whom were eligible for entry onto the study ) were well balanced for prognostic factors . Of 84 patients with measurable lesions , six ( 7 . 1 % ) achieved partial responses ( three patients at each dose level ) . Time to progression was longer for docetaxel patients than for best supportive care patients ( 10.6 v 6.7 weeks , respectively ; P < .001 ) , as was median survival ( 7.0 v 4.6 months ; log-rank test , P = .047 ) . The difference was more significant for docetaxel 75 mg/m(2 ) patients , compared with corresponding best supportive care patients ( 7.5 v 4.6 months ; log-rank test , P = .010 ; 1-year survival , 37 % v 11 % ; chi(2 ) test , P = .003 ) . Febrile neutropenia occurred in 11 patients treated with docetaxel 100 mg/m(2 ) , three of whom died , and in one patient treated with docetaxel 75 mg/m(2 ) . Grade 3 or 4 nonhematologic toxicity , with the exception of diarrhea , occurred at a similar rate in both the docetaxel and best supportive care groups . CONCLUSION Treatment with docetaxel is associated with significant prolongation of survival , and at a dose of 75 mg/m(2 ) , the benefits of docetaxel therapy outweigh the risks CONTEXT More persons in the United States die from non-small cell lung cancer ( NSCLC ) than from breast , colorectal , and prostate cancer combined . In pre clinical testing , oral gefitinib inhibited the growth of NSCLC tumors that express the epidermal growth factor receptor ( EGFR ) , a mediator of cell signaling , and phase 1 trials have demonstrated that a fraction of patients with NSCLC progressing after chemotherapy experience both a decrease in lung cancer symptoms and radiographic tumor shrinkages with gefitinib . OBJECTIVE To assess differences in symptomatic and radiographic response among patients with NSCLC receiving 250-mg and 500-mg daily doses of gefitinib .  DESIGN , SETTING , AND PATIENTS Double-blind , r and omized phase 2 trial conducted from November 2000 to April 2001 in 30 US academic and community oncology centers . Patients ( N = 221 ) had either stage IIIB or IV NSCLC for which they had received at least 2 chemotherapy regimens . INTERVENTION Daily oral gefitinib , either 500 mg ( administered as two 250-mg gefitinib tablets ) or 250 mg ( administered as one 250-mg gefitinib tablet and 1 matching placebo ) . MAIN OUTCOME MEASURES Improvement of NSCLC symptoms ( 2-point or greater increase in score on the summed lung cancer subscale of the Functional Assessment of Cancer Therapy-Lung [ FACT-L ] instrument ) and tumor regression ( > 50 % decrease in lesion size on imaging studies ) . RESULTS Of 2 
    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: Response rate and toxicity of second-line therapy with docetaxel ( 75 mg m−2 ) or docetaxel , irinotecan , and lenogastrim ( 60 mg m−2 , 200 mg m−2 , and 150 μg m−2 day−1 , respectively ) were compared in 108 patients with stage IIIb – IV non-small-cell lung cancer . Addition of irinotecan to docetaxel does not improve response rate , and increases gastrointestinal toxicity 7034 Background : D is now the st and ard second-line treatment for NSCLC patients based upon improved survival and quality of life in two phase III studies . DG has been also promising in several phase II trials in second-line setting . In order to evaluate whether combination regimen of DG provides better overall survival than D in patients with previously treated NSCLC , we conducted a r and omized trial . METHODS Eligibility included pathologically or cytologically proven NSCLC , stage IV or IIIB , one prior platinum-based regimen chemotherapy , performance status 0 or 1 , 20 - 75 years old . Patients were r and omized to receive either D ( 60 mg/m2 , day 1 ) or DG ( D 60 mg/m2 , day 8 , G 800 mg/m2 , days 1 , 8) , repeated every 21 days until disease progression . RESULTS 65 patients were accrued in each arm between Jan. 2002 and Apr. 2003 ( planned ; 142 per arm ) ; one was ineligible due to stage IIIA . This trial was terminated early with unexpected high incidence of interstitial lung disease ( ILD ) and 3 treatment related death ( 5 % ) due to ILD only in DG arm , which were identified by Adverse Event Reporting system . DG compared with D patients experienced similar grade 3 - 4 neutropenia ( DG 70 % , D 75 % ) , grade 2 - 4 nausea ( 17 % , 15 % ) , anorexia ( 20 % , 23 % ) , constipation ( 21 % , 30 % ) , alopecia ( 23 % , 24 % ) , febrile neutropenia ( 15 % , 25 % ) , but more dyspnea ( 23 % , 14 % ) and ILD ( 21 % , 2 % ) . There was no baseline factor identified for predicting ILD . The hazard ratio ( HR ) for overall survival was 0.89 ( 95 % CI 0.52 , 1.55 , logrank p = 0.69 ) in favor of DG . Median survival was 11.3 ( DG ) and 10.1 months ( D ) . One-year survival rate was 47 % and 38 % . The HR for progression free survival ( PFS ) was 0.68 ( 95 % CI 0.46 , 0.99 , p = 0.04 ) . Median PFS was 3.1 ( DG ) and 2.1 ( D ) months . CONCLUSIONS The combination of D and G may be too toxic regimen due to high risk of ILD for previously treated patients . D alone is still considered to be the st and ard second-line treatment for NSCLC . No significant financial relationships to disclose BACKGROUND We conducted a r and omized , placebo-controlled , double-blind trial to determine whether the epidermal growth factor receptor inhibitor erlotinib prolongs survival in non-small-cell lung cancer after the failure of first-line or second-line chemotherapy . METHODS Patients with stage IIIB or IV non-small-cell lung cancer , with performance status from 0 to 3 , were eligible if they had received one or two prior chemotherapy regimens .  The patients were stratified according to center , performance status , response to prior chemotherapy , number of prior regimens , and prior platinum-based therapy and were r and omly assigned in a 2:1 ratio to receive oral erlotinib , at a dose of 150 mg daily , or placebo . RESULTS The median age of the 731 patients who underwent r and omization was 61.4 years ; 49 percent had received two prior chemotherapy regimens , and 93 percent had received platinum-based chemotherapy .  The response rate was 8.9 percent in the erlotinib group and less than 1 percent in the placebo group ( P<0.001 ) ; the median duration of the response was 7.9 months and 3.7 months , respectively . Progression-free survival was 2.2 months and 1.8 months , respectively ( hazard ratio , 0.61 , adjusted for stratification categories ; P<0.001 ) . Overall survival was 6.7 months and 4.7 months , respectively ( hazard ratio , 0.70 ; P<0.001 ) , in favor of erlotinib . Five percent of patients discontinued erlotinib because of toxic effects . CONCLUSIONS Erlotinib can prolong survival in patients with non-small-cell lung cancer after first-line or second-line chemotherapy PURPOSE To evaluate the efficacy and tolerability of two doses of gefitinib ( Iressa [ ZD1839 ] ; AstraZeneca , Wilmington , DE ) , a novel epidermal growth factor receptor tyrosine kinase inhibitor , in patients with pretreated advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS This was a r and omized , double-blind , parallel-group , multicenter phase II trial . Two hundred ten patients with advanced NSCLC who were previously treated with one or two chemotherapy regimens ( at least one containing platinum )  were r and omly assigned to receive either 250-mg or 500-mg oral doses of gefitinib once daily . RESULTS Efficacy was similar for the 250- and 500-mg/d groups . Objective tumor response rates were 18.4 % ( 95 % confidence interval [ CI ] , 11.5 to 27.3 ) and 19.0 % ( 95 % CI , 12.1 to 27.9 ) ; among evaluable patients , symptom improvement rates were 40.3 % ( 95 % CI , 28.5 to 53.0 ) and 37.0 % ( 95 % CI , 26.0 to 49.1 ) ; median progression-free survival times were 2.7 and 2.8 months ; and median overall survival times were 7.6 and 8.0 months , respectively . Symptom improvements were recorded for 69.2 % ( 250 mg/d ) and 85.7 % ( 500 mg/d ) of patients with a tumor response . Adverse events ( AEs ) at both dose levels were generally mild ( grade 1 or 2 ) and consisted mainly of skin reactions and diarrhea . Drug-related toxicities were more frequent in the higher-dose group . Withdrawal due to drug-related AEs was 1.9 % and 9.4 % for patients receiving gefitinib 250 and 500 mg/d , respectively . CONCLUSION Gefitinib showed clinical ly meaningful antitumor activity and provided symptom relief as second- and third-line treatment in these patients . At 250 mg/d , gefitinib had a favorable AE profile . Gefitinib 250 mg/d is an important , novel treatment option for patients with pretreated advanced NSCLC [ corrected PURPOSE To confirm the promising phase II results of docetaxel monotherapy , this phase III trial was conducted of chemotherapy for patients with advanced non-small-cell lung cancer ( NSCLC ) who had previously failed platinum-containing chemotherapy . PATIENTS AND METHODS A total of 373 patients were r and omized to receive either docetaxel 100 mg/m(2 ) ( D100 ) or 75 mg/m(2 ) ( D75 ) versus a control regimen of vinorelbine or ifosfamide ( V/I ) . The three treatment groups were well-balanced for key patient characteristics . RESULTS Overall response rates were 10.8 % with D100 and 6.7 % with D75 , each significantly higher than the 0.8 % response with V/I ( P = .001 and P = .036 , respectively ) . Patients who received docetaxel had a longer time to progression ( P = .046 , by log-rank test ) and a greater progression-free survival at 26 weeks ( P = .005 , by chi(2 ) test ) . Although overall survival was not significantly different between the three groups , the 1-year survival was significantly greater with D75 than with the control treatment ( 32 % v 19 % ; P = .025 , by chi(2 ) test ) . Prior exposure to paclitaxel did not decrease the likelihood of response to docetaxel , nor did it impact survival . There was a trend toward greater efficacy in patients whose disease was platinum-resistant rather than platinum-refractory and in patients with performance status of 0 or 1 versus 2 . Toxicity was greatest with D100 , but the D75 arm was well-tolerated . CONCLUSION This first r and omized trial in this setting demonstrates that D75 every 3 weeks can offer clinical ly meaningful benefit to patients with advanced NSCLC whose disease has relapsed or progressed after platinum-based chemotherapy PURPOSE To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non-small-cell lung cancer who had previously been treated with platinum-based chemotherapy .  Secondary end points included assessment of response ( docetaxel arm only ) , toxicity , and quality of life . PATIENTS AND METHODS Patients with performance statuses of 0 to 2 and stage IIIB/IV non-small-cell lung cancer with either measurable or evaluable lesions were eligible for entry onto the study if they had undergone one or more platinum-based chemotherapy regimens and if they had adequate hematology and biochemistry parameters . They were excluded if they had symptomatic brain metastases or if they had previously been treated with paclitaxel .  Patients were stratified by performance status and best response to cisplatin chemotherapy and were then r and omized to treatment with docetaxel 100 mg/m(2 ) ( 49 patients ) or 75 mg/m(2 ) ( 55 patients ) or best supportive care . Patients in both arms were assessed every 3 weeks . RESULTS One hundred four patients ( 103 of whom were eligible for entry onto the study ) were well balanced for prognostic factors . Of 84 patients with measurable lesions , six ( 7 . 1 % ) achieved partial responses ( three patients at each dose level ) . Time to progression was longer for docetaxel patients than for best supportive care patients ( 10.6 v 6.7 weeks , respectively ; P < .001 ) , as was median survival ( 7.0 v 4.6 months ; log-rank test , P = .047 ) . The difference was more significant for docetaxel 75 mg/m(2 ) patients , compared with corresponding best supportive care patients ( 7.5 v 4.6 months ; log-rank test , P = .010 ; 1-year survival , 37 % v 11 % ; chi(2 ) test , P = .003 ) . Febrile neutropenia occurred in 11 patients treated with docetaxel 100 mg/m(2 ) , three of whom died , and in one patient treated with docetaxel 75 mg/m(2 ) . Grade 3 or 4 nonhematologic toxicity , with the exception of diarrhea , occurred at a similar rate in both the docetaxel and best supportive care groups . CONCLUSION Treatment with docetaxel is associated with significant prolongation of survival , and at a dose of 75 mg/m(2 ) , the benefits of docetaxel therapy outweigh the risks CONTEXT More persons in the United States die from non-small cell lung cancer ( NSCLC ) than from breast , colorectal , and prostate cancer combined . In pre clinical testing , oral gefitinib inhibited the growth of NSCLC tumors that express the epidermal growth factor receptor ( EGFR ) , a mediator of cell signaling , and phase 1 trials have demonstrated that a fraction of patients with NSCLC progressing after chemotherapy experience both a decrease in lung cancer symptoms and radiographic tumor shrinkages with gefitinib . OBJECTIVE To assess differences in symptomatic and radiographic response among patients with NSCLC receiving 250-mg and 500-mg daily doses of gefitinib .  DESIGN , SETTING , AND PATIENTS Double-blind , r and omized phase 2 trial conducted from November 2000 to April 2001 in 30 US academic and community oncology centers . Patients ( N = 221 ) had either stage IIIB or IV NSCLC for which they had received at least 2 chemotherapy regimens . INTERVENTION Daily oral gefitinib , either 500 mg ( administered as two 250-mg gefitinib tablets ) or 250 mg ( administered as one 250-mg gefitinib tablet and 1 matching placebo ) . MAIN OUTCOME MEASURES Improvement of NSCLC symptoms ( 2-point or greater increase in score on the summed lung cancer subscale of the Functional Assessment of Cancer Therapy-Lung [ FACT-L ] instrument ) and tumor regression ( > 50 % decrease in lesion size on imaging studies ) . RESULTS Of 2 
    Output:
    