***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 The objective of this study was to evaluate the efficacy and toxicity of infusional 5-fluorouracil ( 5-FU ) , folinic acid and oxaliplatin ( modified FOLFOX-6 ) in patients with advanced gastric cancer ( AGC ) , as first-line palliative combination chemotherapy . We also analyzed the predictive or prognostic value of germline polymorphisms of c and i date genes associated with 5-FU and oxaliplatin . Methods Seventy-three patients were administered a 2 hour infusion of oxaliplatin ( 100 mg/m2 ) and folinic acid ( 100 mg/m2 ) followed by a 46 hour continuous infusion of 5-FU ( 2,400 mg/m2 ) . Genomic DNA from the patients ' peripheral blood mononuclear cells was extracted . Ten polymorphisms within five genes were investigated including TS , GSTP , ERCC , XPD and XRCC . Results The overall response rate ( RR ) was 43.8 % . Median time to progression ( TTP ) and overall survival ( OS ) were 6.0 months and 12.6 months , respectively . Toxicities were generally tolerable and manageable . The RR was significantly higher in patients with a 6-bp deletion homozygote ( -6 bp/-6 bp ) in TS-3'UTR ( 55.0 % vs. 30.3 % in + 6 bp/+6 bp or + 6 bp/-6 bp , p = 0.034 ) , and C/A or A/A in XPD156 ( 52.0 % vs. 26.1 % in C/C , p = 0.038 ) . The -6 bp/-6 bp in TS-3'UTR was significantly associated with a prolonged TTP and OS . In a multivariate analysis , the 6-bp deletion in TS-3'UTR was identified as an independent prognostic marker of TTP ( hazard ratio = 0.561 , p = 0.032 ) . Conclusion Modified FOLFOX-6 chemotherapy appears to be active and well tolerated as first line chemotherapy in AGC patients . The 6-bp deletion in TS-3'UTR might be a c and i date to select patients who are likely to benefit from 5-FU based modified FOLFOX-6 in future large scale trial Purpose : To investigate the prognostic role of thymidylate synthase ( TS ) polymorphisms in gastric cancer patients treated with radical surgery and fluorouracil-based adjuvant chemotherapy .  Experimental Design : Ninety gastric cancer cases were identified among 187 patients previously enrolled in prospect i ve case-control studies for disease susceptibility . Patients were genotyped for a G/C nucleotide change within a triple 28 bp variable number of t and em repeat sequence in the TS 5′-untranslated region ( 5′-UTR ) and a 6 bp deletion in the TS 3′-untranslated region ( 3′-UTR ) . According to available functional data , patients with 5′-UTR 2R/2R , 2R/3C , 3C/3C genotypes were classified as low TS producers ( 5′-UTRlow ) and patients with 5′-UTR 3G/3 G , 3G/3C , 2R/3 G genotypes as high TS producers ( 5′UTRhigh ) . Patients with 3′-UTR del6/del6 and del6/ins6 genotypes were classified as low TS producers ( 3′-UTRlow ) and patients with 3′-UTR ins6/ins6 genotype as high TS producers ( 3′-UTRhigh ) . The prognostic analysis was based on 5′-UTR/3′-UTR combined genotypes . Results : Ten patients ( 11 % ) were 5′-UTRhigh/3′-UTRhigh , 36 patients were 5′-UTRhigh/3′-UTRlow , 19 patients were 5′-UTRlow/3′-UTRhigh , and 25 patients were 5′-UTRlow/3′-UTRlow . 5′-UTRlow/3′-UTRlow patients showed the best outcome and the threshold of statistical significance was achieved in the comparison of disease-free survival and overall survival with 5′-UTRhigh/3′-UTRlow patients and 5′-UTRhigh/3′-UTRhigh patients . The presence of at least one high TS expression genotype showed independent adverse prognostic role in multivariate analysis . Conclusions : The prognostic role of TS polymorphisms in gastric cancer deserves further investigation because the adverse effect of high TS expression genotypes may be a relevant information to improve adjuvant chemotherapeutic strategies In this marker evaluation study , we tested whether distinct patterns of functional genomic polymorphisms in genes involved in drug metabolic pathways and DNA repair that predict clinical outcome to 5-fluorouracil (5-FU)/oxaliplatin chemotherapy in patients with advanced colorectal cancer could be identified . Functional polymorphisms in DNA-repair genes XPD , ERCC1 , XRCC1 , XPA , and metabolising genes glutathione S-transferase GSTP1 , GSTT1 , GSTM1 , and thymidylate synthase ( TS ) were assessed retrospectively in 106 patients with refractory stage IV disease who received 5-FU/oxaliplatin combination chemotherapy , using a polymerase chain reaction-based RFLP technique .  Favourable genotypes from polymorphisms in XPD-751 , ERCC1 - 118 , GSTP1 - 105 , and TS-3′-untranslated region ( 3′UTR ) that are associated with overall survival were identified . After adjustment for performance status , the relative risks of dying for patients who possessed the unfavourable genotype were : 3.33 for XPD-751 ( P=0.037 ) , 3.25 for GSTP1 - 105 ( P=0.072 ) , 2.05 for ERCC1 - 118 ( P=0.037 ) , and 1.65 for TS-3′UTR ( P=0.091 ) when compared to their respective beneficial genomic variants . Combination analysis with all four polymorphisms revealed that patients possessing ⩾2 favourable genotypes survived a median of 17.4 months ( 95 % confidence interval ( CI ) : 9.4 , 26.5 ) compared to 5.4 months ( 95 % CI : 4.3 , 6.0 ) in patients with no favourable genotype . Patients who carried one favourable genotype demonstrated intermediate survival of 10.2 months ( 95 % CI : 6.8 , 15.3 ; P<0.001 ) . Polymorphisms in the TS-3′UTR and GSTP1 - 105 gene were also associated with time to progression . After adjustment for performance status , patients with an unfavourable TS-3′UTR genotype had a relative risk of disease progression of 1.76 ( P=0.020 ) and those with the unfavourable GSTP1 - 105 genotype showed a relative risk of progression of 2.00 ( P=0.018 ) . The genomic polymorphisms XPD-751 , ERCC1 - 118 , GSTP1 - 105 , and TS-3′UTR may be useful in predicting overall survival and time to progression of colorectal cancer in patients who receive 5-FU/oxaliplatin chemotherapy .  These findings require independent prospect i ve confirmation Oxaliplatin and irinotecan have proven effective in the treatment of gastric cancer . We attempted to determine whether single nucleotide polymorphisms in ERCC1 , GST , TS and UGT1A1 predicted overall survival in gastric cancer patients receiving FOLFOX and /or FOLFIRI chemotherapy .  Total genomic DNA was extracted from the whole blood of patients . The PCR-restriction fragment length polymorphism technique was applied in order to detect the known variant sites of ERCC1 , GST , TS and UGT1A1 . The response rate of FOLFOX  ( N=75 ) was 24 % . Grade 3 - 4 neutropenia and neurotoxicity were observed at frequencies of 34.7 and 16 % , respectively . TTP and OS of first-line administration of FOLFOX ( N=35 ) were 3.1 months ( 95 % CI , 0.1 - 6.1 months ) and 13.9 months ( 95 % CI , 12.2 - 15.6 months ) , respectively . Only the GSTM1 positive genotype exhibited a significantly better time to progression ( P=0.023 ) . However , significant genotypic variation of TS , GST and ERCC1 , which was assumed to affect the activity of oxaliplatin , was not observed to affect RR , toxicity and overall survival . The response rate of FOLFIRI ( N=74 ) was 23 % . Grade 3 - 4 neutropenia and diarrhea were observed in 55.4 and 9.5 % of cases , respectively . TTP and OS of first-line administration of FOLFIRI ( N=33 ) was 4.9 months ( 95 % CI , 3.5 - 6.4 months ) and 19.0 months ( 95 % CI , 8.5 - 29.5 months ) . The low expression type ( 2R/2R , 2R/3C and 3C/3C ) of TS was associated with a high incidence of grade > or=3 neutropenia . However , significant genotypic variation of UGT1A1 , which was assumed to affect irinotecan toxicity , was not observed to affect RR , toxicity or survival . In this study , the GSTM1 positive genotype evidence d a significantly better time to progression in cases of advanced gastric cancer being treated with FOLFOX . The low expression type ( 2R/2R , 2R/3C and 3C/3C ) of TS was associated with a high incidence of grade > or=3 neutropenia in cases of advanced gastric cancer treated with FOLFIRI BACKGROUND This clinical trial assessed the efficacy of pemetrexed combined with oxaliplatin ( PEMOX ) in patients with advanced gastric cancer ( AGC ) . PATIENTS AND METHODS Forty-four patients with untreated AGC were enrolled to evaluate response rate ( RR ) . Patients received pemetrexed ( 500 mg/m(2 ) ) with vitamin supplementation and oxaliplatin ( 120 mg/m(2 ) ) every 21 days for six cycles or until disease progression occurred . RESULTS Median age was 62 years ( range 26 - 76 ) . The majority of patients ( 93 % ) had metastatic disease . Sixteen of the 44 patients achieved confirmed response [ RR 36 % ; 95 % confidence interval ( CI ) 22 % to 52 % ] ; four complete responses and 12 partial responses ( complete and partial responses according to the RECIST guidelines are the confirmed-responses observed in the study population ) . Median time to tumor progression ( TTP ) was 6.2 months ( 95 % CI 4.3 - 7.5 ) and median survival was 10.8 months ( 95 % CI 7.7 - 17.2 ) . A total of 220 cycles were administered , with a median of six cycles . Most common grade 3/4 toxic effects were neutropenia in 41 % of patients ( 19 % of cycles ) and thrombocytopenia in 11 % of patients ( 4 % of cycles ) . Treatment delays or dose reductions for toxicity occurred in 10 % and 5 % of cycles , respectively . CONCLUSIONS PEMOX is active and well tolerated in AGC .  RR , TTP , and survival were comparable to those achieved in studies using different 5-fluorouracil (5-FU)-oxaliplatin combinations , without the inconvenience of prolonged 5-FU schedules Purpose The aim of this study was to assess whether genetic polymorphisms in p53 , glutathione S-transferase P1 ( GSTP1 ) , GSTM1 , excision repair cross complementing group 1 ( ERCC1 ) and X-ray repair cross-complementing group 1 ( XRCC1 ) genes are associated with clinical outcome of gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy .  Methods The genetic polymorphisms in p53 , GSTP1,GSTM1 ( null ) , ERCC1 and XRCC1 were determined in 102 gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy using polymerase chain reaction-ligation detection reaction method .  Results Among the five studied polymorphisms , p53 codon 72 Pro/Pro , GSTP1 codon 105 Ile/Ile , and XRCC1 codon 399 Gln/Gln + Arg/Gln were associated with poor relapse-free survival and overall survival ( P < 0.05 ) ; and the prognostic effect was retained in the Cox multivariate analysis . Combination analysis with the three polymorphisms using the Kaplan – Meier method and Cox multivariate analysis revealed that the relapse-free and overall survivals significantly increase with the number of favorable genotypes ( P < 0.05 ) . No significant association was found between the GSTM1 ( null ) or the ERCC1 codon 118 genotypes and the clinical outcome ( P > 0.05 ) . Conclusion Testing for p53 Arg72Pro 
    Output:
    
Conclusion Polymorphisms of ERCC1 , GSTs , TS and MTHFR were closely associated with clinical outcomes of GC patients treated with platinum/5-Fu-based chemotherapy .
Studies with large sample size using the method of multi-variant analyses may help us to give more persuasive data on the putative association in future