***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: PURPOSE This phase III trial compared the efficacy and safety of gemcitabine ( Gem ) plus capecitabine ( GemCap ) versus single-agent Gem in advanced/metastatic pancreatic cancer . PATIENTS AND METHODS Patients were r and omly assigned to receive GemCap ( oral capecitabine 650 mg/m2 twice daily on days 1 to 14 plus Gem 1,000 mg/m2 by 30-minute infusion on days 1 and 8 every 3 weeks ) or Gem ( 1,000 mg/m2 by 30-minute infusion weekly for 7 weeks , followed by a 1-week break , and then weekly for 3 weeks every 4 weeks ) . Patients were stratified according to center , Karnofsky performance score ( KPS ) , presence of pain , and disease extent . RESULTS A total of 319 patients were enrolled between June 2001 and June 2004 .  Median overall survival ( OS ) time , the primary end point , was 8.4 and 7.2 months in the GemCap and Gem arms , respectively ( P = .234 ) . Post hoc analysis in patients with good KPS ( score of 90 to 100 ) showed a significant prolongation of median OS time in the GemCap arm compared with the Gem arm ( 10.1 v 7.4 months , respectively ; P = .014 ) . The overall frequency of grade 3 or 4 adverse events was similar in each arm . Neutropenia was the most frequent grade 3 or 4 adverse event in both arms . CONCLUSION GemCap failed to improve OS at a statistically significant level compared with st and ard Gem treatment . The safety of GemCap and Gem was similar . In the subgroup of patients with good performance status , median OS was improved significantly . GemCap is a practical regimen that may be considered as an alternative to single-agent Gem for the treatment of advanced/metastatic pancreatic cancer patients with a good performance status Erlotinib combined with gemcitabine has not been evaluated in Japanese patients with unresectable pancreatic cancer . This two‐step phase II study assessed the safety and pharmacokinetics of erlotinib 100 mg/day ( oral ) plus gemcitabine 1000 mg/m2 ( i.v . days 1 , 8 , 15 ) in a 28‐day cycle in the first step , and efficacy and safety in the second step . The primary end‐point was safety . One hundred and seven patients were enrolled ( first step , n = 6 ; second step , n = 101 ) . The most common adverse event was RASH ( compiled using the preferred terms rash , acne , exfoliative rash , dermatitis acneiform , erythema , eczema , dermatitis and pustular rash ) in 93.4 % of patients . One treatment‐related death occurred . While interstitial lung disease‐like events were reported in nine patients ( 8.5 % ; grade 1/2/3 , 3.8/2.8/1.9 % ) , all patients recovered or improved . The median overall survival , the 1‐year survival rate and median progression‐free survival were 9.23 months , 33.0 % and 3.48 months , respectively . The overall response and disease control rates were 20.3 % and 50.0 % , respectively . In Japanese patients with unresectable pancreatic cancer  , erlotinib plus gemcitabine  had acceptable toxicity and efficacy that was not inferior to that seen in Western patients . ( Cancer Sci 2011 ; 102 : 425–431 Pancreatic cancer is the fifth most common cause of cancer death in the western world and the prognosis for unresectable disease remains poor . Recent advances in conventional chemotherapy and the development of novel ‘ molecular ’ treatment strategies with different toxicity profiles warrant investigation as combination treatment strategies . This r and omised study in pancreatic cancer compares marimastat ( orally administered matrix metalloproteinase inhibitor ) in combination with gemcitabine to gemcitabine alone .  Two hundred and thirty-nine patients with unresectable pancreatic cancer were r and omised to receive gemcitabine ( 1000 mg m−2 ) in combination with either marimastat or placebo . The primary end-point was survival . Objective tumour response and duration of response , time to treatment failure and disease progression , quality of life and safety were also assessed . There was no significant difference in survival between gemcitabine and marimastat and gemcitabine and placebo ( P=0.95 log-rank test ) . Median survival times were 165.5 and 164 days and 1-year survival was 18 % and 17 % respectively . There were no significant differences in overall response rates ( 11 and 16 % respectively ) , progression-free survival ( P=0.68 log-rank test ) or time to treatment failure ( P=0.70 log-rank test ) between the treatment arms . The gemcitabine and marimastat combination was well tolerated with only 2.5 % of patients withdrawn due to presumed marimastat toxicity . Grade 3 or 4 musculoskeletal toxicities were reported in only 4 % of the marimastat treated patients , although 59 % of marimastat treated patients reported some musculoskeletal events . The results of this study provide no evidence to support a combination of marimastat with gemcitabine in patients with advanced pancreatic cancer . The combination of marimastat with gemcitabine was well tolerated . Further studies of marimastat as a maintenance treatment following a response or stable disease on gemcitabine may be justified Pancreatic cancer is a highly lethal malignancy with few effective therapies . We performed exome sequencing and copy number analysis to define genomic aberrations in a prospect ively accrued clinical cohort ( n = 142 ) of early ( stage I and II ) sporadic pancreatic ductal adenocarcinoma . Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations . We define 16 significantly mutated genes , reaffirming known mutations ( KRAS , TP53 , CDKN2A , SMAD4 , MLL3 , TGFBR2 , ARID1A and SF3B1 ) , and uncover novel mutated genes including additional genes involved in chromatin modification ( EPC1 and ARID2 ) , DNA damage repair ( ATM ) and other mechanisms ( ZIM2 , MAP2K4 , NALCN , SLC16A4 and MAGEA6 ) . Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis . Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma , and identified new mutated genes in each pathway . We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance , particularly SLIT/ROBO signalling , which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer , providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis BACKGROUND The ESPAC-3 trial showed that adjuvant gemcitabine is the st and ard of care based on similar survival to and less toxicity than adjuvant 5-fluorouracil/folinic acid in patients with resected pancreatic cancer . Other clinical trials have shown better survival and tumour response with gemcitabine and capecitabine than with gemcitabine alone in advanced or metastatic pancreatic cancer . We aim ed to determine the efficacy and safety of gemcitabine and capecitabine compared with gemcitabine monotherapy for resected pancreatic cancer . METHODS We did a phase 3 , two-group , open-label , multicentre , r and omised clinical trial at 92 hospitals in Engl and , Scotl and , Wales , Germany , France , and Sweden . Eligible patients were aged 18 years or older and had undergone complete macroscopic resection for ductal adenocarcinoma of the pancreas ( R0 or R1 resection ) . We r and omly assigned patients ( 1:1 ) within 12 weeks of surgery to receive six cycles of either 1000 mg/m2 gemcitabine alone administered once a week for three of every 4 weeks ( one cycle ) or with 1660 mg/m2 oral capecitabine administered for 21 days followed by 7 days ' rest ( one cycle ) . R and omisation was based on a minimisation routine , and country was used as a stratification factor . The primary endpoint was overall survival , measured as the time from r and omisation until death from any cause , and assessed in the intention-to-treat population . Toxicity was analysed in all patients who received trial treatment . This trial was registered with the EudraCT , number 2007 - 004299 - 38 , and IS RCT N , number IS RCT N96397434 . FINDINGS Of 732 patients enrolled , 730 were included in the final analysis . Of these , 366 were r and omly assigned to receive gemcitabine and 364 to gemcitabine plus capecitabine . The Independent Data and Safety Monitoring Committee requested reporting of the results after there were 458 ( 95 % ) of a target of 480 deaths . The median overall survival for patients in the gemcitabine plus capecitabine group was 28·0 months ( 95 % CI 23·5 - 31·5 ) compared with 25·5 months ( 22·7 - 27·9 ) in the gemcitabine group ( hazard ratio 0·82 [ 95 % CI 0·68 - 0·98 ] , p=0·032 ) . 608 grade 3 - 4 adverse events were reported by 226 of 359 patients in the gemcitabine plus capecitabine group compared with 481 grade 3 - 4 adverse events in 196 of 366 patients in the gemcitabine group . INTERPRETATION The adjuvant combination of gemcitabine and capecitabine should be the new st and ard of care following resection for pancreatic ductal adenocarcinoma . FUNDING Cancer Research UK BACKGROUND Pre clinical data have suggested a synergistic effect of cetuximab combined with gemcitabine and cisplatin and clinical data have shown a substantial improvement in response and survival when gemcitabine is combined with a platinum analogue compared with gemcitabine alone . The aim of this study was to assess the activity and feasibility of a combination of cetuximab with gemcitabine and cisplatin compared with use of gemcitabine and cisplatin alone for the treatment of advanced pancreatic cancer . METHODS In a multicentre , r and omised phase II trial , 84 patients with advanced pancreatic cancer were r and omly assigned to either 250 mg/m2 cetuximab weekly , after a loading dose of 400 mg/m2 , plus 1000 mg/m2 gemcitabine and 35 mg/m2 cisplatin on days 1 and 8 of a 21-day cycle or to the same chemotherapeutic regimen without cetuximab . The primary endpoint was objective response ( defined as the proportion of patients whose best response was either partial response or complete response ) . Secondary endpoints included disease control ( defined as the proportion of patients whose best response was either partial response , complete response , or stable disease ) , progression-free survival , and overall survival . All assessment s of response at each site were done blindly by a local experienced radiologist who was not directly involved in the trial . Responses were measured according to an intention-to-treat analysis . This trial is registered with the Clinical Trial registry , number NCT00536614 . FINDINGS 29 men and 13 women were r and omly assigned to cetuximab plus gemcitabine and cisplatin ( median age 61 years [ range 38 - 78 ] ) and 22 men and 20 women were r and omly assigned to gemcitabine and cisplatin ( median age 64 years [ range 40 - 76 ] ) . Seven of 40 ( 17.5 % ) patients had an objective response in the cetuximab group ( 95 % CI 7.3 - 32.8 ) and five of 41 ( 12.2 % ) patients had an objective response in the non-cetuximab group ( 95 % CI 4.1 - 26.2 ) . No significant difference was noted between the groups both for objective response ( 5.3 % higher in the cetuximab group [ 95 % CI -16.5 to 27.1 ] ; chi2 test=0.360 ; p=0.549 ) or for disease control ( 3.5 % higher in the non-cetuximab group [ -34.0 % to 27.0 % ] ; 0.446 ; p=0.504 ) . Overall median follow-up was 11.8 months ( range 2.5 - 18.5 ) . No significant differences between the groups were noted in median progression-free survival ( hazard ratio 0.96 , 95 % CI 0.60 - 1.52 , p=0.847 ) or in median overall survival ( 0.91 , 0.54 - 1.55 , p=0.739 ) : median progression-free survival was 3.4 months ( 95 % CI 2.4 - 5.1 ) in the cetuximab group and 4.2 months ( 2.6 - 5.4 ) in the non-cetuximab group ; median overall surv 
    Output:
    
Neither G3/4 rash nor diarrhoea were associated with increased survival benefit from EGFR-targeted therapy .