***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 Targeting epidermal growth factor receptors ( EGFRs ) has been a novel strategy in treating non-small-cell lung cancer ( NSCLC ) . This multicenter , community-based trial was design ed to examine the role of cetuximab in combination with a nonplatinum regimen . PATIENTS AND METHODS Eligibility criteria were newly diagnosed unresectable stage III/IV NSCLC , all histologies , measurable disease , and Eastern Cooperative Oncology Group performance status ( ECOG PS ) 0 - 2 . Treatment premedication included dexamethasone 20 mg orally 12 and 6 hours before treatment , and 4 mg 12 hours following treatment ; diphenhydramine 50 mg intravenously ( I.V. ) and cimetidine 300 mg I.V. before cetuximab . Treatment medication included docetaxel 30 mg/m2 I.V. days 1 and 8 ; gemcitabine 1000 mg/m2 I.V. days 1 and 8 ; and cetuximab 400 mg/m2 I.V. day 1 , then 250 mg/m2 I.V. weekly . Patients received up to 6 cycles with restaging every 6 weeks . The primary endpoint was an overall response rate ( ORR ) > or = 25 % . RESULTS Sixty-nine patients enrolled from July 2005 to October 2007 . Patients had a median age of 69 years ; 70 % were male and 30 % were female ; ECOG PS was 0 in 42 % , 1 in 51 % , and 2 in 7 % ; patients had adenocarcinoma ( 42 % ) , squamous cell ( 30 % ) , large cell ( 6 % ) , mixed ( 1 % ) , and not otherwise specified ( 20 % ) disease . The ORR was 17 % ( 95 % CI , 9%-29 % ) . Thirty-five patients ( 54 % ) had stable disease ; 14 patients ( 22 % ) had progressive disease . With a median follow-up of 17.8 months , the median progression-free and overall survivals were 4 months and 9.4 months , respectively . The most common ( > 10 % ) grade 3/4 toxicities were neutropenia ( 25 % ) , rash ( 22 % ) , and fatigue ( 12 % ) . Accrual in our middle Tennessee offices was temporarily suspended and ultimately stopped because of a higher-than-anticipated rate of cetuximab-related severe hypersensitivity reactions ( HSRs ) in 4 patients among the first 12 enrolled , including 1 fatal event . CONCLUSION Cetuximab/docetaxel/gemcitabine was relatively well-tolerated and associated with efficacy similar to chemotherapy alone . Additional study with cetuximab/chemotherapy in NSCLC should focus on new potentially predictive biomarkers . Also , additional study is needed to better underst and and prevent the severe HSRs that appear to be endemic to specific regions of the United States PURPOSE Epidermal growth factor receptor ( EGFR ) mutations have been associated with tumor response to treatment with single-agent EGFR inhibitors in patients with relapsed non-small-cell lung cancer ( NSCLC ) . The implication s of EGFR mutations in patients treated with EGFR inhibitors plus first-line chemotherapy are unknown . KRAS is frequently activated in NSCLC . The relationship of KRAS mutations to outcome after EGFR inhibitor treatment has not been described . PATIENTS AND METHODS Previously untreated patients with advanced NSCLC in the phase III TRIBUTE study who were r and omly assigned to carboplatin and paclitaxel with erlotinib or placebo  were assessed for survival , response , and time to progression ( TTP ) . EGFR exons 18 through 21 and KRAS exon 2 were sequenced in tumors from 274 patients . Outcomes were correlated with EGFR and KRAS mutations in retrospective subset analyses . RESULTS EGFR mutations were detected in 13 % of tumors and were associated with longer survival , irrespective of treatment ( P < .001 ) . Among erlotinib-treated patients , EGFR mutations were associated with improved response rate ( P < .05 ) and there was a trend toward an erlotinib benefit on TTP ( P = .092 ) , but not improved survival ( P = .96 ) . KRAS mutations ( 21 % of tumors ) were associated with significantly decreased TTP and survival in erlotinib plus chemotherapy-treated patients . CONCLUSION EGFR mutations may be a positive prognostic factor for survival in advanced NSCLC patients treated with chemotherapy with or without erlotinib , and may predict greater likelihood of response . Patients with KRAS-mutant NSCLC showed poorer clinical outcomes when treated with erlotinib and chemotherapy . Further studies are needed to confirm the findings of this retrospective subset analysis ABSTRACT Purpose : To investigate the activity of carboplatin and cetuximab in NSCLC . Patients and Methods : This was a single arm , multicenter phase II trial , and the primary objective was response rate . Results : The overall response rate observed was 9 % ( 95 % confidence interval [ CI ] , 3–19 ) , the progression-free survival was 2.9 months ( 95 % CI , 1.9–3.6 ) , the median overall survival was 8.2 months ( 95 % CI , 4.9–10.5 ) , and 1-year survival rate was 33 % ( 95 % CI , 21–45 ) . Conclusion : The combination of carboplatin and cetuximab demonstrated lower activity than double agent platinum-based therapy and does not warrant further development PURPOSE To evaluate the efficacy of cetuximab plus taxane/carboplatin ( TC ) as first-line treatment of advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS This multicenter , open-label , phase III study enrolled 676 chemotherapy-naïve patients with stage IIIB ( pleural effusion ) or IV NSCLC , without restrictions by histology or epidermal growth factor receptor expression . Patients were r and omly assigned to cetuximab/TC or TC . TC consisted of paclitaxel ( 225 mg/m(2 ) ) or docetaxel ( 75 mg/m(2 ) ) , at the investigator 's discretion , and carboplatin ( area under the curve = 6 ) on day 1 every 3 weeks for < or = six cycles ; cetuximab ( 400 mg/m(2 ) on day 1 , 250 mg/m(2 ) weekly ) was administered until progression or unacceptable toxicity . The primary end point was progression-free survival assessed by independent radiologic review committee ( PFS-IRRC ) ; overall response rate ( ORR ) , overall survival ( OS ) , quality of life ( QoL ) , and safety were key secondary end points . PFS and ORR assessed by investigators were also evaluated . Results Median PFS-IRRC was 4.40 months with cetuximab/TC versus 4.24 months with TC ( hazard ratio [ HR ] = 0.902 ; 95 % CI , 0.761 to 1.069 ; P = .236 ) . Median OS was 9.69 months with cetuximab/TC versus 8.38 months with TC ( HR = 0.890 ; 95 % CI , 0.754 to 1.051 ; P = .169 ) . ORR-IRRC was 25.7 % with cetuximab/TC versus 17.2 % with TC ( P = .007 ) . The safety profile of this combination was manageable and consistent with its individual components . CONCLUSION The addition of cetuximab to TC did not significantly improve the primary end point , PFS-IRRC . There was significant improvement in ORR by IRRC . The difference in OS favored cetuximab but did not reach statistical significance BACKGROUND The Lung Cancer Cetuximab Study is an open-label , r and omized phase II pilot study of cisplatin and vinorelbine combined with the epidermal growth factor receptor (EGFR)-targeted monoclonal antibody cetuximab versus cisplatin and vinorelbine alone , in patients with advanced EGFR-expressing , non-small-cell lung cancer ( NSCLC ) . End points of the study are activity , safety and pharmacokinetics . PATIENTS AND METHODS Following r and omization , for a maximum of eight cycles , patients received three-weekly cycles of cisplatin ( 80 mg/m(2 ) , day 1 ) and vinorelbine ( 25 mg/m(2 ) on days 1 and 8) alone or following cetuximab treatment ( initial dose 400 mg/m(2 ) , followed by 250 mg/m(2 ) weekly thereafter ) . RESULTS Eighty-six patients were r and omly allocated to the study ( 43 per arm ) . Confirmed response rates were 28 % in the cisplatin/vinorelbine arm ( A ) and 35 % in the cetuximab plus cisplatin/vinorelbine arm ( B ) . Median progression-free survival ( PFS ) was 4.6 months in arm A and 5.0 months in arm B , with PFS rates at 12 months of 0 % and 15 % , respectively . Median survival was 7.3 months in arm A and 8.3 months in arm B. The 24-month survival rates were 0 % and 16 % , respectively . The cetuximab combination was well tolerated . CONCLUSION In the first-line treatment of advanced NSCLC , the combination of cetuximab plus cisplatin/vinorelbine demonstrated an acceptable safety profile and the potential to improve activity over cisplatin/vinorelbine alone PURPOSE The epidermal growth factor ( EGF ) receptor is frequently overexpressed in epithelial tumors . C225 is a human-to-murine chimeric monoclonal antibody that binds to the receptor and inhibits growth of cancer cells expressing the receptor . We evaluated the pharmacokinetics and toxicity of C225 in patients with advanced tumors overexpressing EGF receptors . PATIENTS AND METHODS We treated 52 patients in three successive phase I clinical trials of C225  as a single dose ( n = 13 ) , weekly multiple dose ( n = 17 ) , and weekly multiple dose with cisplatin ( n = 22 ) . C225 dose levels were 5 , 20 , 50 , and 100 mg/m(2 ) . In the study combining C225 with cisplatin , limited to patients with either head and neck or non-small-cell lung cancer , C225 was further escalated to 200 and 400 mg/m(2 ) . Cisplatin was given at a dose of 60 mg/m(2 ) once every 4 weeks , and treatment was continued for up to 12 weeks if no disease progression occurred . RESULTS C225 displayed nonlinear pharmacokinetics , with antibody doses in the range of 200 to 400 mg/m(2 ) being associated with complete saturation of systemic clearance . C225 clearance did not change with repeated administration or with coadministration of cisplatin .  Antibodies against C225 were detected in only one patient , and C225-associated toxicity was minimal . Patients experiencing disease stabilization were seen in all studies . In the study combining C225 and cisplatin , nine ( 69 % ) of 13 patients treated with antibody doses > /= 50 mg/m(2 ) completed 12 weeks of therapy , and two partial responses were observed . CONCLUSION C225 has dose-dependent pharmacokinetics , and doses that achieve saturation of systemic clearance are well tolerated .  C225 given in combination with cisplatin has biologic activity at pharmacologically relevant doses PURPOSE Epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitors have demonstrated antitumor activity in patients with non-small-cell lung cancer ( NSCLC ) . This study examined the safety profile of the monoclonal antibody EGFR inhibitor , cetuximab , when added to paclitaxel and carboplatin in untreated patients with stage IV NSCLC . Secondary objectives included efficacy and paclitaxel and carboplatin pharmacokinetics during cetuximab treatment . PATIENTS AND METHODS Patients with tumor evidence of EGFR by immunohistochemistry , performance status of 0 to 2 , and measurable disease received paclitaxel 225 mg/m2 with carboplatin area under the curve = 6 on day 1 every 3 weeks . Cetuximab was administered at 400 mg/m2 , 1 week before paclitaxel and carboplatin , then weekly at 250 mg/m2 . The regimen continued until disease progression or intolerable toxicity . RESULTS Thirty-one of 32 enrolled patients were treated . The most common cetuximab toxicity was rash in 84 % of patients ( grade 3 in 13 % ) . Pharmacokinetic sampling did not reveal an interaction between carboplatin , paclitaxel , and cetuximab . An objective response was observed in eight patients ( 26 % ) . With a median follow-up of 19 months , the median time to 
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The difference in other adverse events did not reach statistical significance .
According to the reports of original studies , the adverse events were generally manageable .
There were no cetuximab-related deaths .
AUTHORS ' CONCLUSIONS The combination of chemotherapy plus cetuximab is better than chemotherapy alone as the first-line treatment of advanced NSCLC in improving overall survival , while inducing higher rates of some reportedly manageable adverse events