***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: This trial assessed pharmacokinetic interactions between  cetuximab and irinotecan . Patients were placed in either in group A ( irinotecan 350 mg/m2/3 weeks and 400 mg/m2 cetuximab at week 2 then 250 mg/m2/week ) or group B ( cetuximab weekly starting week 1 then irinotecan starting week 4 ) . Patient plasma or serum sample s from each treatment arm were analysed using HPLC and ELISA . Among 14 patients , compartmental model showed no significant differences in mean plasma AUC at week 1 versus week 4 for irinotecan ( 44,388 versus 39,800 microg/ml/h ) and cetuximab ( 20,441 versus 23,363 microg/ml/h ) , respectively . Half-lifes ( st and ard deviations ) for irinotecan were 16.02 ( + /-8.41 ) h at week 1 and 13.99 ( + /-2.14 ) h at week 4 , and for cetuximab 106 ( + /-32 ) at week 3 and 111 ( + /-30 ) h at week 4 . Mean concentration-versus-time profiles either alone or in combination were superimposable for cetuximab and irinotecan . From this study , we conclude that there is no evidence of pharmacokinetic interaction between irinotecan and cetuximab BACKGROUND Treatment with cetuximab , a monoclonal antibody directed against the epidermal growth factor receptor , improves overall and progression-free survival and preserves the quality of life in patients with colorectal cancer that has not responded to chemotherapy . The mutation status of the K-ras gene in the tumor may affect the response to cetuximab and have treatment-independent prognostic value . METHODS We analyzed tumor sample s , obtained from 394 of 572 patients ( 68.9 % ) with colorectal cancer who were r and omly assigned to receive cetuximab plus best supportive care or best supportive care alone  , to look for activating mutations in exon 2 of the K-ras gene . We assessed whether the mutation status of the K-ras gene was associated with survival in the cetuximab and supportive-care groups . RESULTS Of the tumors evaluated for K-ras mutations , 42.3 % had at least one mutation in exon 2 of the gene . The effectiveness of cetuximab was significantly associated with K-ras mutation status ( P=0.01 and P<0.001 for the interaction of K-ras mutation status with overall survival and progression-free survival , respectively ) . In patients with wild-type K-ras tumors , treatment with cetuximab as compared with supportive care alone significantly improved overall survival ( median , 9.5 vs. 4.8 months ; hazard ratio for death , 0.55 ; 95 % confidence interval [ CI ] , 0.41 to 0.74 ; P<0.001 ) and progression-free survival ( median , 3.7 months vs. 1.9 months ; hazard ratio for progression or death , 0.40 ; 95 % CI , 0.30 to 0.54 ; P<0.001 ) . Among patients with mutated K-ras tumors , there was no significant difference between those who were treated with cetuximab and those who received supportive care alone with respect to overall survival ( hazard ratio , 0.98 ; P=0.89 ) or progression-free survival ( hazard ratio , 0.99 ; P=0.96 ) . In the group of patients receiving best supportive care alone , the mutation status of the K-ras gene was not significantly associated with overall survival ( hazard ratio for death , 1.01 ; P=0.97 ) . CONCLUSIONS Patients with a colorectal tumor bearing mutated K-ras did not benefit from cetuximab , whereas patients with a tumor bearing wild-type K-ras did benefit from cetuximab . The mutation status of the K-ras gene had no influence on survival among patients treated with best supportive care alone . ( Clinical Trials.gov number , NCT00079066 . 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 BACKGROUND Cetuximab , an IgG1 chimeric monoclonal antibody against epidermal growth factor receptor ( EGFR ) , has activity against colorectal cancers that express EGFR . METHODS From December 2003 to August 2005 , 572 patients who had colorectal cancer expressing immunohistochemically detectable EGFR and who had been previously treated with a fluoropyrimidine , irinotecan , and oxaliplatin or had contraindications to treatment with these drugs underwent r and omization to an initial dose of 400 mg of cetuximab per square meter of body-surface area followed by a weekly infusion of 250 mg per square meter plus best supportive care  ( 287 patients ) or best supportive care alone  ( 285 patients ) . The primary end point was overall survival . RESULTS In comparison with best supportive care alone , cetuximab treatment was associated with a significant improvement in overall survival ( hazard ratio for death , 0.77 ; 95 % confidence interval [ CI ] , 0.64 to 0.92 ; P=0.005 ) and in progression-free survival ( hazard ratio for disease progression or death , 0.68 ; 95 % CI , 0.57 to 0.80 ; P<0.001 ) . These benefits were robust after adjustment in a multivariable Cox proportional-hazards model . The median overall survival was 6.1 months in the cetuximab group and 4.6 months in the group assigned to supportive care alone . Partial responses occurred in 23 patients ( 8.0 % ) in the cetuximab group but in none in the group assigned to supportive care alone ( P<0.001 ) ; the disease was stable in an additional 31.4 % of patients assigned to cetuximab and in 10.9 % of patients assigned to supportive care alone ( P<0.001 ) . Quality of life was better preserved in the cetuximab group , with less deterioration in physical function and global health status scores ( both P<0.05 ) . Cetuximab treatment was associated with a characteristic rash ; a rash of grade 2 or higher was strongly associated with improved survival ( hazard ratio for death , 0.33 ; 95 % CI , 0.22 to 0.50 ; P<0.001 ) . The incidence of any adverse event of grade 3 or higher was 78.5 % in the cetuximab group and 59.1 % in the group assigned to supportive care alone ( P<0.001 ) . CONCLUSIONS Cetuximab improves overall survival and progression-free survival and preserves quality -of-life measures in patients with colorectal cancer in whom other treatments have failed . ( Clinical Trials.gov number , NCT00079066 [ Clinical Trials.gov ] . ) BACKGROUND This two-part phase Ib/II study investigated the feasibility of administering cetuximab in combination with oxaliplatin and infusional 5-fluorouracil (5-FU)/folinic acid ( FA ) in a weekly schedule ( AIO FUFOX protocol ) as first-line treatment in patients with epidermal growth factor receptor-detectable advanced colorectal cancer . PATIENTS AND METHODS Cetuximab was administered weekly : 400 mg/m(2 ) initial dose , then 250 mg/m(2 ) and FUFOX : oxaliplatin 50 mg/m(2 ) , FA 500 mg/m(2 ) and 5-FU as a 24-h infusion at either 1500 or 2000 mg/m(2 ) administered for 4 weeks followed by a 1-week rest ( one cycle ) . RESULTS Dose-limiting toxicity ( grade 3 diarrhea ) occurred in 3 of 14 assessable patients receiving 5-FU at st and ard 2000 mg/m(2 ) . This dose was administered to a further 25 patients . Cetuximab combined with FUFOX was generally well tolerated with the most common grade 3/4 adverse events being diarrhea ( 27 % ) and paresthesia ( 16 % ) . The confirmed response rate for patients receiving 5-FU at st and ard 2000 mg/m(2 ) ( N = 41 ) was 56 % , with a median duration of 9.3 months . Median progression-free and overall survival times including all 49 patients were 8.1 ( 95 % confidence interval 6.0 - 9.7 ) and 28.2 months , respectively . Cetuximab pharmacokinetics seemed not to be different for combination with FUFOX compared with cetuximab/irinotecan combinations . CONCLUSION This protocol is well tolerated and shows promising efficacy supporting further investigation PURPOSE To determine the efficacy of cetuximab in patients with recurrent or progressive non-small-cell lung cancer ( NSCLC ) after receiving at least one prior chemotherapy regimen . PATIENTS AND METHODS This was an open-label , phase II study of patients with epidermal growth factor receptor ( EGFR ) -positive and EGFR-negative advanced NSCLC with Eastern Cooperative Oncology 
    Output:
    
Addition of cytotoxic chemotherapy to cetuximab significantly increases the risk of high- grade acneiform rash compared with cetuximab monotherapy .