***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 Pre clinical data indicate EGFR signals through both kinase-dependent and independent pathways and that combining a small-molecule EGFR inhibitor , EGFR antibody , and /or anti-angiogenic agent is synergistic in animal models . METHODS We conducted a dose-escalation , phase I study combining erlotinib , cetuximab , and bevacizumab . The subset of patients with non-small cell lung cancer ( NSCLC ) was analyzed for safety and response . RESULTS Thirty-four patients with NSCLC ( median four prior therapies ) received treatment on a range of dose levels . The most common treatment-related grade ≥2 adverse events were rash ( n=14 , 41 % ) , hypomagnesemia ( n=9 , 27 % ) , and fatigue ( n=5 , 15 % ) . Seven patients ( 21 % ) achieved stable disease ( SD ) ≥6 months , two achieved a partial response ( PR ) ( 6 % ) , and two achieved an unconfirmed partial response ( uPR ) ( 6 % ) ( total=32 % ) . We observed SD≥6 months/PR/uPR in patients who had received prior erlotinib and /or bevacizumab , those with brain metastases , smokers , and patients treated at lower dose levels . Five of 16 patients ( 31 % ) with wild-type EGFR experienced SD≥6 months or uPR . Correlation between grade of rash and rate of SD≥6 months/PR was observed ( p<0.01 ) . CONCLUSION The combination of erlotinib , cetuximab , and bevacizumab was well-tolerated and demonstrated antitumor activity in heavily pretreated patients with NSCLC PURPOSE To evaluate the efficacy and safety of cetuximab , a monoclonal antibody that inhibits the epidermal growth factor receptor ( EGFR ) , as a first-line monotherapy in patients with unresectable squamous cell carcinoma of the skin ( SCCS ) . PATIENTS AND METHODS Thirty-six patients received cetuximab  ( initial dose of 400 mg/m(2 ) followed by subsequent weekly doses of 250 mg/m(2 ) ) for at least 6 weeks with a 48-week follow-up . The primary end point was the disease control rate ( DCR ) at 6 weeks ( according to Response Evaluation Criteria in Solid Tumors [ RECIST ] criteria ) . Secondary end points included best response rate , overall survival , progression-free survival ( PFS ) , and toxicity assessment . Association of treatment efficacy with RAS mutations or FcγR genotypes was investigated . RESULTS Median age of the study population was 79 years .  DCR at 6 weeks was obtained in 25 of 36 patients ( 69 % ; 95 % CI , 52 % to 84 % ) of the intention-to-treat population . The best responses were eight partial responses and two complete responses . There were no cetuximab-related deaths . There were three related serious adverse events : two grade 4 infusion reactions and one grade 3 interstitial pneumopathy . Grade 1 to 2 acne-like rash occurred in 78 % of patients and was associated with prolonged PFS . One HRAS mutation was identified . Combined FcγRIIa-131H/H and /or FcγRIIIa-158V/V polymorphisms were not associated with the clinical outcomes . CONCLUSION As a first-line treatment in patients with unresectable SCCS , cetuximab achieved 69 % DCR . A r and omized phase III trial is warranted to confirm that cetuximab may be considered as a therapeutic option especially in elderly patients . The low frequency of RAS mutations in SCCS makes SCCS tumors attractive for EGFR inhibition BACKGROUND According to the results of a number of phase 3 r and omized studies , sorafenib is the only approved systemic therapy for advanced HCC ; however the issue of high economic cost remains challenging ; thus we have conducted this retrospective analysis of our HCC patients treated with sorafenib . METHODS HCC patients treated at Ain Shams University Hospitals , in the period between 2010 and 2012 were review ed . Eligible patients were those who had received sorafenib for advanced HCC not eligible for or progressed after surgery or locoregional therapy . We investigated the impact of baseline clinicopathological factors ( age , gender , child status , performance score , BCLC tumor stage , cause of chronic liver disease , median baseline alpha fetoprotein level and previous treatment received for HCC ) on overall survival ( OS ) in an adjusted Cox regression model . RESULTS 41 patients were included in the analysis fulfilling the inclusion criteria . At a median follow up period of 13 months , the median PFS for the whole group was 4 months ; the median OS for the whole group is 6.25 months . Multivariate analysis identified three baseline characteristics that were prognostic indicators for overall survival : ECOG performance status ( median OS for ECOG 1=7.01 months and for ECOG 2=3.03 months ) , Child-Pugh status ( median OS for child A=12.04 months and for child B=5.23 months ) , and median baseline levels of alpha-fetoprotein . CONCLUSIONS In limited re source countries like Egypt , we suggest that the use of sorafenib for the treatment of advanced HCC cases should be restricted to a highly selected subgroup of patients with good performance and child BACKGROUND The purpose of this phase II trial was to evaluate the efficacy and safety of cetuximab and irinotecan as second-line treatment in patients with gastro-oesophageal adenocarcinoma . PATIENTS AND METHODS Patients with failure to first-line platinum-based chemotherapy received cetuximab 500 mg/m(2 ) and irinotecan 180 mg/m(2 ) every second week until disease progression . Toxicity was evaluated according to The Cancer Institute Common Terminology Criteria for Adverse Events ( NCI-CTCAE ) v. 3.0 . Antitumour activity was assessed according to Response Evaluation Criteria in Solid Tumours ( RECIST ) v. 1.0 . RESULTS Sixty-three patients were enrolled , median age was 60 years , median performance status was 1 ( 0 - 1 ) , 35 patients had two or more organs involved . The median number of courses was 5 ( range 1 - 25 ) . Response rate was 11 % ( 6 partial response ( PR ) ) and 37 % had stable disease . Median progression free survival was 2.8 months and overall survival ( OS ) was 6.1 months . Grade 3 - 4 toxicity included : diarrhoea ( 6 % ) , fatigue ( 5 % ) , vomiting ( 5 % ) and neutropenia ( 16 % ) . Two patients developed febrile neutropenia . Forty-six patients ( 73 % ) had developed grade 1 - 2 skin rash . Patients developing skin rash had a prolonged survival with an OS at 7.1 months . CONCLUSIONS The combination of cetuximab and irinotecan is active as second-line therapy in patients with gastro-oesophageal cancer . Cetuximab induced skin rash was associated with prolonged survival The only approved systemic therapy for patients with advanced hepatocellular carcinoma ( HCC ) till now is sorafenib . A preliminary study suggested that capecitabine , an oral fluoropyrimidine , may be effective in advanced HCC . We have tested this hypothesis in this phase 2 study . In this single-center , phase 2 , open-label trial , we r and omly assigned 52 patients with advanced HCC who had not received previous systemic treatment to receive either sorafenib ( at a dose of 400 mg twice daily ) or capecitabine ( 1,000 mg/m2 twice daily ) ( day 1–day 14 ) . Primary outcome was progression-free survival . Secondary outcomes included the overall survival and safety . Median overall survival was 7.05 months in the sorafenib group and 5.07 months in the capecitabine group ( hazard ratio in the capecitabine group 2.36 ; 95 % confidence interval 1.174–4.74 ; P < 0.016 ) . The median progression-free survival was 6 months in the sorafenib group and 4 months in the capecitabine group ( P < 0.005 ) . Three patients in the sorafenib group ( 11.5 % ) and one patient in the capecitabine group ( 3 % ) had a partial response ; one patient ( 3 % ) had a complete response in the sorafenib group . H and –foot skin reaction was more frequent in the sorafenib group , hyperbilirubinemia was more common in the capecitabine group , and diarrhea was equivalent between both groups . In patients with advanced HCC , capecitabine is inferior to sorafenib in terms of median progression-free survival and overall survival , and it should not be used alone for the treatment of advanced HCC , but rather , combination therapy with sorafenib should be considered BACKGROUND Previous results from our phase 3 r and omised trial showed that adding cetuximab to primary radiotherapy increased overall survival in patients with locoregionally advanced squamous-cell carcinoma of the head and neck ( LASCCHN ) at 3 years . Here we report the 5-year survival data , and investigate the relation between cetuximab-induced rash and survival . METHODS Patients with LASCCHN of the oropharynx , hypopharynx , or larynx with measurable disease were r and omly allocated in a 1:1 ratio to receive either  comprehensive head and neck radiotherapy alone  for 6 - 7 weeks or radiotherapy plus weekly doses of cetuximab : 400 mg/m(2 ) initial dose , followed by seven weekly doses at 250 mg/m(2 ) . R and omisation was done with an adaptive minimisation technique to balance assignments across stratification factors of Karnofsky performance score , T stage , N stage , and radiation fractionation . The trial was un-blinded . The primary endpoint was locoregional control , with a secondary endpoint of survival . Following discussion s with the US Food and Drug Administration , the data set was locked , except for queries to the sites about overall survival , before our previous report in 2006 , so that an independent review could be done . Analyses were done on an intention-to-treat basis . Following completion of treatment , patients underwent physical examination and radiographic imaging every 4 months for 2 years , and then every 6 months thereafter . The trial is registered at www . Clinical Trials.gov , number NCT00004227 . FINDINGS Patients were r and omly assigned to receive radiotherapy with ( n=211 ) or without ( n=213 ) cetuximab , and all patients were followed for survival . Up date d median overall survival for patients treated with cetuximab and radiotherapy was 49.0 months ( 95 % CI 32.8 - 69.5 ) versus 29.3 months ( 20.6 - 41.4 ) in the radiotherapy-alone group ( hazard ratio [ HR ] 0.73 , 95 % CI 0.56 - 0.95 ; p=0.018 ) . 5-year overall survival was 45.6 % in the cetuximab-plus-radiotherapy group and 36.4 % in the radiotherapy-alone group . Additionally , for the patients treated with cetuximab , overall survival was significantly improved in those who experienced an acneiform rash of at least grade 2 severity compared with patients with no rash or grade 1 rash ( HR 0.49 , 0.34 - 0.72 ; p=0.002 ) . INTERPRETATION For patients with LASCCHN , cetuximab plus radiotherapy significantly improves overall survival at 5 years compared with radiotherapy alone , confirming cetuximab plus radiotherapy as an important treatment option in this group of patients . Cetuximab-treated patients with prominent cetuximab-induced rash ( grade 2 or above ) have better survival than patients with no or grade 1 rash . FUNDING ImClone Systems , Merck KGaA , and Bristol-Myers Squibb BACKGROUND The r and omised phase 3 First-Line Erbitux in Lung Cancer ( FLEX ) study showed that the addition of cetuximab to cisplatin and vinorelbine significantly improved overall survival compared with chemotherapy alone in the first-line treatment of advanced non-small-cell lung cancer ( NSCLC ) . The main cetuximab-related side-effect was acne-like rash . Here , we assessed the association of this acne-like rash with clinical benefit . METHODS We did a subgroup analysis of patients in the FLEX study , which enrolled patients with advanced NSCLC whose tumours expressed epidermal growth factor receptor . Our l and mark analysis assessed if the development of acne-like rash in the first 21 days of treatment ( first-cycle rash ) was associated with clinical outcome , on the basis of patients in the intention-to-treat population alive on day 21 . The FLEX study is registered with Clinical Trials.gov , number NCT00148798 . FINDINGS 518 patients in the chemotherapy plus cetuximab group-290 of whom had first-cycle rash- and 540 patients in the chemotherapy alone group were alive on day 21 . Patients in the chemotherapy plus cetuximab group with first-cycle rash had significantly prolonged overall survival compared with patients in the same treatment group without first-cycle rash ( median 15·0 months [ 95 % CI 12·8 - 16·4 ] 
    Output:
    
Exploratory subgroup analysis showed no effect of tumor types on the RR of ORR .
Our meta- analysis has demonstrated that cetuximab-induced rash is associated with a significantly improved OS , PFS and ORR .
Cetuximab-induced skin rash may represent a prognostic factor in patients with advanced solid tumors