***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 We conducted a r and omized study to determine whether any of three chemotherapy regimens was superior to cisplatin and paclitaxel in patients with advanced non-small-cell lung cancer . METHODS A total of 1207 patients with advanced non-small-cell lung cancer were r and omly assigned to a reference regimen of cisplatin and paclitaxel or to one of three experimental regimens : cisplatin and gemcitabine , cisplatin and docetaxel , or carboplatin and paclitaxel . RESULTS The response rate for all 1155 eligible patients was 19 percent , with a median survival of 7.9 months ( 95 percent confidence interval , 7.3 to 8.5 ) , a 1-year survival rate of 33 percent ( 95 percent confidence interval , 30 to 36 percent ) , and a 2-year survival rate of 11 percent ( 95 percent confidence interval , 8 to 12 percent ) . The response rate and survival did not differ significantly between patients assigned to receive cisplatin and paclitaxel and those assigned to receive any of the three experimental regimens . Treatment with cisplatin and gemcitabine was associated with a significantly longer time to the progression of disease than was treatment with cisplatin and paclitaxel but was more likely to cause grade 3 , 4 , or 5 renal toxicity ( in 9 percent of patients , vs. 3 percent of those treated with cisplatin plus paclitaxel ) . Patients with a performance status of 2 had a significantly lower rate of survival than did those with a performance status of 0 or 1 . CONCLUSIONS None of four chemotherapy regimens offered a significant advantage over the others in the treatment of advanced non-small-cell lung cancer PURPOSE We performed a r and omized phase II trial comparing pemetrexed with pemetrexed plus carboplatin ( PC ) in patients experiencing relapse after platinum-based chemotherapy .  PATIENTS AND METHODS Main eligibility criteria were histologic or cytologic proof of advanced non-small-cell lung cancer ( NSCLC ) , relapse more than 3 months after platinum-based chemotherapy , normal organ function , and Eastern Cooperative Oncology Group performance status 0 to 2 . Patients were r and omly assigned to pemetrexed 500 mg/m(2 ) ( arm A ) or carboplatin area under the curve 5 and pemetrexed 500 mg/m(2 ) ( arm B ) , both administered intravenously every 3 weeks . Response assessment was performed every 6 weeks ; toxicity assessment was performed every 3 weeks . Primary end point was time to progression ( TTP ) ; secondary end points were objective response rate ( ORR ) , overall survival ( OS ) , and toxicity . The study was design ed to detect a 33 % decrease in the hazard of disease progression in the combination arm ( alpha = 0.05 , two-sided log-rank test ) . Polymorphisms of thymidylate synthase , the reduced folate carrier , gamma-glutamyl hydrolase , and methylenetetrahydrofolate reductase ( MTHF ) were investigated in peripheral WBCs of consenting patients . RESULTS Two hundred forty patients were enrolled .  Median TTP was 2.8 months for arm A versus 4.2 months for arm B ( hazard ratio , 0.67 ; 95 % CI , 0.51 to 0.89 ; P = .005 ) . Median OS was 7.6 months and 8.0 months and ORR was 4 % and 9 % for arms A and B , respectively . Subgroup analyses found adenocarcinoma to be associated with favorable outcome . Toxicities in both arms was negligible , with one potential toxic death in arm A. Patients with MTHFR C677 T homozygous mutation had increased progression-free survival compared with patients with wild-type or heterozygous mutations ( P = .03 ) . CONCLUSION PC as second-line treatment for relapsed NSCLC result ed in a significant 33 % reduction of the hazard of disease progression as compared with pemetrexed alone BACKGROUND This is a phase II r and omized study to evaluate the efficacy and safety of bortezomib and pemetrexed alone or in combination , in patients with previously treated advanced non-small-cell lung cancer ( NSCLC ) . The primary end point was assessment of response rate . METHODS A total of 155 patients were r and omized ( 1:1:1 ) to pemetrexed ( 500mg/m(2 ) ) on day 1 plus bortezomib ( 1.6mg/m(2 ) ) on days 1 and 8 ( Arm A ) or pemetrexed ( 500mg/m(2 ) ) on day 1 ( Arm B ) or bortezomib ( 1.6mg/m(2 ) ) on days 1 and 8 ( Arm C ) of a 21 day cycle . Response rate was assessed by investigators using Response Evaluation Criteria In Solid Tumors ( RECIST ) criteria and toxicity assessed by the National Cancer Institute-Common Terminology Criteria for Adverse Events ( NCI-CTCAE ) grading system . RESULTS Response rate was 7 % in Arm A , 4 % in Arm B , and 0 % in Arm C ; disease control rates were 73 % , 62 % , and 43 % , respectively . Median overall survival was 8.6 months in Arm A , 12.7 months in Arm B , and 7.8 months in Arm C ; time to progression was 4.0 months , 2.9 months , and 1.4 months , respectively . Most common reported adverse events > /= grade 3 were neutropenia ( 19 % ) , thrombocytopenia ( 15 % ) , and dyspnea ( 13 % ) in Arm A , neutropenia ( 10 % ) in Arm B , and dyspnea ( 13 % ) and fatigue ( 10 % ) in Arm C. CONCLUSION In previously treated NSCLC the addition of bortezomib to pemetrexed was well tolerated but offered no statistically significant response or survival advantage versus pemetrexed alone , while bortezomib alone showed no clinical ly significant activity Introduction : This r and omized phase II study investigated pemetrexed in combination with the epidermal growth factor receptor (EGFR)-targeting monoclonal antibody matuzumab compared with pemetrexed alone as second-line therapy for patients with advanced non-small cell lung cancer . Methods : Patients received pemetrexed 500 mg/m2 every 3 weeks either alone ( n = 50 ) or in combination with matuzumab at either 800 mg weekly ( n = 51 ) or 1600 mg every 3 weeks ( n = 47 ) . The primary end point was objective response , as assessed by an independent review committee . Results : Tumor EGFR expression was detected in 87 % of r and omized patients . The objective response rate for the pooled matuzumab-treated arms was 11 % compared with 5 % for pemetrexed alone ( p = 0.332 ) . Apart from one patient in the pemetrexed alone group , all responses occurred in patients whose tumors expressed EGFR . The objective response rate for patients receiving weekly matuzumab was 16 % compared with 2 % for those receiving matuzumab every 3 weeks . There was also a trend for improved overall survival in patients receiving matuzumab weekly versus every 3 weeks ( 12.4 months versus 5.9 months , respectively , versus 7.9 months for pemetrexed alone ) . The combination of pemetrexed and matuzumab demonstrated an acceptable safety profile , with the most common grade 3/4 adverse event being neutropenia . Conclusion : Although the analysis on the pooled matuzumab-treated arms did not demonstrate a statistically significant improvement in objective response for the addition of matuzumab to pemetrexed compared with pemetrexed alone , the trends for improvement in objective response and overall survival for pemetrexed plus weekly matuzumab compared with pemetrexed alone warrant confirmation in additional clinical trials Introduction : We examined the efficacy of enzastaurin plus pemetrexed as second-line therapy in patients with advanced ( stage IIIA/B or IV ) non-small cell lung cancer in a double-blinded , r and omized , phase II study . Methods : Patients received pemetrexed 500 mg/m2 intravenously on day 1 of 21-day cycles ( day 8 in cycle 1 ) plus oral enzastaurin ( 250 mg two times per day ; combination arm ) or placebo ( pemetrexed arm ) . Both arms received supplementation with vitamin B12 , folic acid , and dexamethasone . An interim analysis was conducted to determine whether efficacy would warrant a phase III study . Results : The interim analysis showed no evidence of improved progression-free survival with enzastaurin . At final analysis ( N = 160 , 80 in each arm ) , baseline characteristics were well balanced . There was no significant difference in progression-free survival ( 3.0 months , p = 0.544 ) or overall survival ( 9.6 months in combination arm and 7.4 months in pemetrexed arm , p = 0.171 ) . Drug-related serious adverse events included cerebrovascular accident , palpitations , and renal failure ( n = 1 , each ) in combination arm and neutropenic sepsis , thrombocytopenia , and panniculitis ( n = 1 , each ) in pemetrexed arm . Nonhematologic drug-related grade 3/4 toxicities were similar in both arms . Grade 3/4 hematologic toxicities were higher with the combination , specifically leukopenia ( 6.3 % versus 0 % ) , neutropenia ( 15.2 % versus 5.0 % ) , and thrombocytopenia ( 8.9 % versus 1.3 % ) . Of the 26 deaths reported on- study or within 30 days of discontinuation ( 10 in combination arm and 16 in pemetrexed arm ) , none were drug related . Conclusion : The combination regimen of enzastaurin and pemetrexed is well tolerated but does not improve efficacy over pemetrexed and placebo as second-line treatment of unselected patients with advanced non-small cell lung cancer PURPOSE To compare the efficacy and toxicity of pemetrexed versus docetaxel in patients with advanced non-small-cell lung cancer ( NSCLC ) previously treated with chemotherapy . PATIENTS AND METHODS Eligible patients had a performance status 0 to 2 , previous treatment with one prior chemotherapy regimen for advanced NSCLC , and adequate organ function . Patients received pemetrexed 500 mg/m(2 ) intravenously ( i.v . ) day 1 with vitamin B(12 ) , folic acid , and dexamethasone or docetaxel 75 mg/m(2 ) i.v . day 1 with dexamethasone every 21 days . The primary end point was overall survival . RESULTS Five hundred seventy-one patients were r and omly assigned . Overall response rates were 9.1 % and 8.8 % ( analysis of variance P = .105 ) for pemetrexed and docetaxel , respectively . Median progression-free survival was 2.9 months for each arm , and median survival time was 8.3 versus 7.9 months ( P = not significant ) for pemetrexed and docetaxel , respectively . The 1-year survival rate for each arm was 29.7 % . Patients receiving docetaxel were more likely to have grade 3 or 4 neutropenia ( 40.2 % v 5.3 % ; P < .001 ) , febrile neutropenia ( 12.7 % v 1.9 % ; P < .001 ) , neutropenia with infections ( 3.3 % v 0.0 % ; P = .004 ) , hospitalizations for neutropenic fever ( 13.4 % v 1.5 % ; P < .001 ) , hospitalizations due to other drug related adverse events ( 10.5 % v 6.4 % ; P = .092 ) , use of granulocyte colony-stimulating factor support ( 19.2 % v 2.6 % , P < .001 ) and all grade alopecia ( 37.7 % v 6.4 % ; P < .001 ) compared with patients receiving pemetrexed . CONCLUSION Treatment with pemetrexed result ed in clinical ly equivalent efficacy outcomes , but with significantly fewer side effects compared with docetaxel in the second-line treatment of patients with advanced NSCLC and should be considered a st and ard treatment option for second-line NSCLC when available PURPOSE Cisplatin plus gemcitabine is a st and ard regimen for first-line treatment of advanced non-small-cell lung cancer ( NSCLC ) . Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting . PATIENTS AND METHODS This noninferiority , phase III , r and omized study compared the overall survival between treatment arms using a fixed margin method ( hazard ratio [ HR ] < 1.176 ) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1 . Patients received cisplatin 75 mg/m(2 ) on day 1 and gemcitabine 1,250 mg/m(2 ) on days 1 and 8 ( n = 863 ) or cisplatin 75 mg/m(2 ) and pemetrex 
    Output:
    
Conclusion Pemetrexed-based doublet therapy did n’t gain any benefit in survival but significantly improved PFS and better ORR compared with single-agent pemetrexed as second-line therapy for advanced non-small-cell lung cancer .
However , more incidences of grade 3 or 4 neutropenia , thrombocytopenia , and leucopenia were observed in pemetrexed-based doublet group