***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 ERCC1 and ERCC2 play critical roles in the nucleotide excision repair pathway that effectively repairs DNA damage induced by chemotherapeutic agents . Therefore , functional single nucleotide polymorphisms ( SNPs ) in these genes could have an impact on clinical outcomes in cancer patients who received chemotherapy .  However , few studies have simultaneously investigated the roles of ERCC1 and ERCC2 SNPs in clinical outcomes in gastric cancer patients . Experimental Design We genotyped by the TaqMan assay three common , potentially functional ERCC1 ( rs3212986 ) and ERCC2 SNPs ( rs13181 and rs1799793 ) in 360 gastric cancer patients . We used both Kaplan-Meier tests and Cox proportional hazards models to evaluate the effects of ERCC1 and ERCC2 genotypes and haplotypes on clinical outcomes . Results We found that , compared with ERCC2 rs1799793 GG+AG genotypes , the homozygous variant AA genotype was associated with significantly poorer overall survival ( OS ) ( AA vs. GG+AG , log-rank P = 0.012 ) and significantly higher risk of death ( AA vs. GG+AG , Adjusted hazards ratio [ HR ] 2.13 ; 95 % CI , 1.28 to 3.56 ; P = 0.004 ) . In combined analyses , patients with any one of the three unfavorable genotypes ( i.e. ERCC1 rs3212986 TT , ERCC2 rs13181 GG and rs1799793 AA ) had statistically significant hazards of poor prognosis ( Adjusted HR , 1.54 ; 95 % CI , 1.06 to 2.25 ; P = 0.025 ) , compared with those without any unfavorable genotypes . Furthermore , the haplotype A-G-G ( rs1799793/rs13181/rs3212986 ) had a significant impact on OS ( Adjusted HR , 1.57 ; 95 % CI , 1.11 to 2.21 ; P = 0.011 ) , compared with the common haplotype G-T-G. Conclusion ERCC1 and ERCC2 functional SNPs may jointly affect OS in Caucasian gastric cancer patients . Additional large prospect i ve studies are essential to confirm our findings PURPOSE Based upon promising pre clinical and phase 1 trial results , combined flavopiridol and cisplatin therapy was evaluated in patients with ovarian and primary peritoneal cancers . METHODS A two cohort phase 2 trial of cisplatin ( 60 mg/m2 IV ) immediately followed by flavopiridol ( 100 mg/m2 IV , 24 h infusion ; 21 day cycles ) was undertaken in patients with recurrent platin-sensitive or platin-resistant disease ( progression > vs . ≤6 months following prior platin-based therapy ) . Measurable disease (RECIST)--or evaluable disease plus CA125>2X post-treatment nadir-- and ECOG performance≤2 were required . RESULTS Forty-five patients were enrolled between December 23 , 2004 and February 25 , 2010 : 40 platin-resistant ( Group 1 ) , and 5 platin-sensitive ( Group 2 ) . In Group 1 , the median number of treatment cycles was 3 ( range 2 - 12 ) . Only 10 % of patients incurred grade 4 toxicities , but grade 3 toxicities were common ( 65 % ) : neutropenia ( 17.5 % ) ; nausea ( 12.5 % ) ; vomiting , fatigue , thrombosis , anemia ( 10 % each ) . Seven patients ( 17.5 % ) achieved a confirmed response ( 1 CR , 6 PR ; median duration 118 days ) ; ten additional patients ( 25 % ) attained maintained stable disease . Median time to progression was 4.3 months ; overall survival was 16.1 months . Pilot translational studies assessed ascites flavopiridol level ; surrogate marker studies were uninformative . In Group 2 , although 4 of 5 patients responded ( 2 confirmed PRs with median time to progression , 10.8 months and median overall survival 20.6 months ) the cohort was closed due to poor accrual . CONCLUSIONS The assessed flavopiridol and cisplatin regimen displayed clinical activity in platin resistant and sensitive ovarian/ primary peritoneal cancers , meriting further study The utilisation of antitumour T cells induced by cancer vaccination with HER-2 peptides or antibodies ( Herceptin ) against HER-2 , as immunotherapy for oesophageal cancer , is a novel and attractive approach . It is important to clarify the frequencies of HER-2 expression and gene amplification in patients with oesophageal squamous cell carcinoma ( SCC ) and to evaluate the relationship between HER-2 status and HLA haplotype , since the c and i date s for HER-2 peptide-based vaccination are restricted to a certain HLA haplotype . We determined the frequency of HER-2 expression using the HercepTest ™ for immunohistochemistry and HER-2 gene amplification by fluorescence in situ hybridisation ( FISH ) assay in oesophageal SCC ( n=66 ) . HER-2-positive tumours ( 1+/2+/3 + ) analysed by a HercepTest were observed in 30.3 % of all the patients and HER-2 gene amplification evaluated by FISH was observed in 11.0 % of all the patients , in which all HercepTest ( 3 + ) tumours were found to have gene amplification and three of six moderately positive ( 2 + ) tumours showed gene amplification . Furthermore , HER-2-positive cells were present more diffusely and were larger within each tumour in the patients who were HercepTest 3 + than those who were HercepTest 1 + . Moreover , the survival rate in HER-2-positive group was significantly worse than that in HER-2-negative group . Also , the survival rate in the patients with HER-2 gene amplification was significantly worse than that without HER-2 gene amplification . In addition , oesophageal SCC patients with both HLA-A24-positive and HER-2-positive tumours ( 1+/2+/3 + ) accounted for 26 % of these cases , and both HLA-A2- and HER-2-positive tumours accounted for 18 % of them BACKGROUND Trastuzumab , a monoclonal antibody against human epidermal growth factor receptor 2 ( HER2 ; also known as ERBB2 ) , was investigated in combination with chemotherapy for first-line treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer . METHODS ToGA ( Trastuzumab for Gastric Cancer ) was an open-label , international , phase 3 , r and omised controlled trial undertaken in 122 centres in 24 countries . Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumours showed overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation . Participants were r and omly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin given every 3 weeks for six cycles or chemotherapy in combination with intravenous trastuzumab . Allocation was by block r and omisation stratified by Eastern Cooperative Oncology Group performance status , chemotherapy regimen , extent of disease , primary cancer site , and measurability of disease , implemented with a central interactive voice recognition system . The primary endpoint was overall survival in all r and omised patients who received study medication at least once . This trial is registered with Clinical Trials.gov , number NCT01041404 . FINDINGS 594 patients were r and omly assigned to study treatment ( trastuzumab plus chemotherapy , n=298 ; chemotherapy alone , n=296 ) , of whom 584 were included in the primary analysis ( n=294 ; n=290 ) . Median follow-up was 18.6 months ( IQR 11 - 25 ) in the trastuzumab plus chemotherapy group and 17.1 months ( 9 - 25 ) in the chemotherapy alone group . Median overall survival was 13.8 months ( 95 % CI 12 - 16 ) in those assigned to trastuzumab plus chemotherapy compared with 11.1 months ( 10 - 13 ) in those assigned to chemotherapy alone ( hazard ratio 0.74 ; 95 % CI 0.60 - 0.91 ; p=0.0046 ) . The most common adverse events in both groups were nausea  ( trastuzumab plus chemotherapy , 197 [ 67 % ] vs chemotherapy alone , 184 [ 63 % ] ) , vomiting ( 147 [ 50 % ] vs 134 [ 46 % ] ) , and neutropenia ( 157 [ 53 % ] vs 165 [ 57 % ] ) . Rates of overall grade 3 or 4 adverse events ( 201 [ 68 % ] vs 198 [ 68 % ] ) and cardiac adverse events ( 17 [ 6 % ] vs 18 [ 6 % ] ) did not differ between groups . INTERPRETATION Trastuzumab in combination with chemotherapy can be considered as a new st and ard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer . FUNDING F Hoffmann-La Roche PURPOSE The efficacy of the epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor ( TKI ) gefitinib was assessed in a phase II study in patients with advanced esophageal cancer . Several biologic features were investigated as potential markers of gefitinib activity . PATIENTS AND METHODS Patients with advanced esophageal cancer , who had failed one line of prior chemotherapy , were administered gefitinib 500 mg/d . Response was evaluated every 8 weeks . Tumor material obtained before gefitinib treatment was investigated for gene mutations in EGFR , k-ras , and PIK3CA ; protein expression levels of EGFR , p-Akt , and p-Erk ; and EGFR gene amplification . RESULTS Of the 36 enrolled patients , one ( 2.8 % ) achieved a partial response , 10 ( 27.8 % ) had stable disease , 17 ( 47.2 % ) experienced progression on treatment , and eight ( 22.2 % ) were not assessable for response . The progression-free survival time was 59 days , and the median overall survival time was 164 days . Although EGFR or PIK3CA mutations were absent , k-ras mutations were found in two patients with progressive disease . High EGFR gene copy number was identified in two patients experiencing partial response or progressive disease . A higher disease control rate ( response plus stable disease ) was observed in females ( P = .038 ) and in patients with squamous cell carcinoma ( SCC ; P = .013 ) or high EGFR expression ( P = .002 ) . CONCLUSION Gefitinib has a modest activity in second-line treatment of advanced esophageal cancer . However , the patient outcome was significantly better in female patients and in patients demonstrating high EGFR expression or SCC histology . The selection of esophageal cancer patients for future studies with EGFR-TKIs based on the level of EGFR expression in their tumors or SCC histology should be considered The present study retrospectively examined the correlation between the outcome of patients with locally advanced oesophageal squamous cell carcinoma ( cT3 - 4 cN0 - 1 cM0 ) after multimodal treatment ( radiochemotherapy±surgical resection )  , and the presence of genetic polymorphisms in genes involved in folate metabolism . In total , 68 patients who took part in a prospect i ve multicentric trial received 5-fluorouracil (FU)-based radiochemotherapy , optionally followed by surgery . DNA was extracted from pretherapeutic tumour biopsies and was subsequently genotyped for common genetic polymorphisms of three genes ( MTHFR C677 T , MTR A2756 G , TS t and em repeat polymorphism ) involved in folate metabolism and potentially in sensitivity to 5-FU-based chemotherapy . The genotypes were correlated with tumour response to polychemotherapy , radiochemotherapy and with overall survival . Tumours with the MTR wild-type genotype ( 2756AA ) showed a median survival time of 16 months , whereas tumours with an MTR variant genotype ( 2756AG/2756GG ) showed a median survival time of 42 months ( P=0.0463 ) . No prognostic impact could be verified for the genotypes of the MTHFR genes and the TS gene . Among tumours treated with radiochemotherapy and subsequent resection , MTR variant genotype showed higher histopathological response rate than tumours with MTR wild-type genotype ( P=0.0442 ) . In contrast , no significant relationship between clinical ly determined tumour regression after polychemotherapy and polymorphisms of the three genes under analysis was observed . In conclusion , pretherapeutic determination of the MTR A2756 G polymorphism may predict survival of multimodally treated oesophageal squamous cell carcinomas . Determination of MTHFR C67 
    Output:
    
Despite this , a small number of variants appear reliable .