{"id":"https://openalex.org/W4238668552","doi":"https://doi.org/10.1200/jco.1994.12.5.960","title":"Meta-analysis of randomized trials testing the biochemical modulation of fluorouracil by methotrexate in metastatic colorectal cancer. Advanced Colorectal Cancer Meta-Analysis Project.","display_name":"Meta-analysis of randomized trials testing the biochemical modulation of fluorouracil by methotrexate in metastatic colorectal cancer. Advanced Colorectal Cancer Meta-Analysis Project.","publication_year":1994,"publication_date":"1994-05-01","ids":{"openalex":"https://openalex.org/W4238668552","doi":"https://doi.org/10.1200/jco.1994.12.5.960","mag":"2460038169","pmid":"https://pubmed.ncbi.nlm.nih.gov/8164048"},"language":"en","primary_location":{"id":"doi:10.1200/jco.1994.12.5.960","doi":"https://doi.org/10.1200/jco.1994.12.5.960","is_oa":false,"landing_page_url":"https://doi.org/10.1200/jco.1994.12.5.960","pdf_url":null,"source":{"id":"https://openalex.org/S15137598","display_name":"Journal of Clinical Oncology","issn_l":"0732-183X","issn":["0732-183X","1527-7755"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Clinical Oncology","raw_type":"journal-article"},"volume":null,"type":"review","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":null,"display_name":"Pascal Piedbois","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Pascal Piedbois","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":null,"display_name":"Marc Buyse","orcid":"https://orcid.org/0000-0002-4559-0994","observed_orcids":["https://orcid.org/0000-0002-4559-0994"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Marc Buyse","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-4559-0994","affiliations":[]},{"author_position":"middle","author":{"id":null,"display_name":"G.H. Blijham","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"G.H. Blijham","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":null,"display_name":"Bengt Glimelius","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Bengt Glimelius","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":null,"display_name":"R. Herrmann","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"R. Herrmann","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":null,"display_name":"Frank H. Valone","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Frank H. Valone","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":null,"display_name":"Robert W. Carlson","orcid":"https://orcid.org/0000-0003-2011-6695","observed_orcids":["https://orcid.org/0000-0003-2011-6695"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Robert W. Carlson","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0003-2011-6695","affiliations":[]},{"author_position":"middle","author":{"id":null,"display_name":"M. Machiavelli","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"M. Machiavelli","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":null,"display_name":"C Delfino","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"C Delfino","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":null,"display_name":"Albert Abad","orcid":"https://orcid.org/0000-0002-0101-3714","observed_orcids":["https://orcid.org/0000-0002-0101-3714"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Albert Abad","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-0101-3714","affiliations":[]},{"author_position":"last","author":{"id":null,"display_name":"Nicholas J. Petrelli","orcid":"https://orcid.org/0000-0002-9830-0807","observed_orcids":["https://orcid.org/0000-0002-9830-0807"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Nicholas J. Petrelli","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-9830-0807","affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":2.6775,"has_fulltext":false,"cited_by_count":243,"citation_normalized_percentile":{"value":0.92553191,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":88,"max":97},"biblio":{"volume":"12","issue":"5","first_page":"960","last_page":"969"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11067","display_name":"Colorectal Cancer Treatments and Studies","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T11067","display_name":"Colorectal Cancer Treatments and Studies","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10335","display_name":"Colorectal Cancer Surgical Treatments","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11845","display_name":"Cancer therapeutics and mechanisms","score":0.0,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/5-fluorouracil","display_name":"5-fluorouracil","score":0.9769999980926514},{"id":"https://openalex.org/keywords/methotrexate","display_name":"methotrexate","score":0.9980000257492065},{"id":"https://openalex.org/keywords/metastatic-colorectal-cancer","display_name":"metastatic colorectal cancer","score":0.8899999856948853},{"id":"https://openalex.org/keywords/combination-chemotherapy","display_name":"combination chemotherapy","score":0.621999979019165},{"id":"https://openalex.org/keywords/tumor-response-rate","display_name":"tumor response rate","score":0.8180000185966492},{"id":"https://openalex.org/keywords/overall-survival","display_name":"overall survival","score":0.9990000128746033},{"id":"https://openalex.org/keywords/chemosensitivity","display_name":"chemosensitivity","score":0.4959999918937683},{"id":"https://openalex.org/keywords/performance-status","display_name":"performance status","score":0.6039999723434448},{"id":"https://openalex.org/keywords/predictors-of-treatment-response","display_name":"predictors of treatment response","score":0.6499999761581421}],"concepts":[{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.9136077165603638},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.7090787291526794},{"id":"https://openalex.org/C526805850","wikidata":"https://www.wikidata.org/wiki/Q188874","display_name":"Colorectal cancer","level":3,"score":0.6909337043762207},{"id":"https://openalex.org/C2780456651","wikidata":"https://www.wikidata.org/wiki/Q238512","display_name":"Fluorouracil","level":3,"score":0.6805849075317383},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.6146228313446045},{"id":"https://openalex.org/C95190672","wikidata":"https://www.wikidata.org/wiki/Q815382","display_name":"Meta-analysis","level":2,"score":0.6024090647697449},{"id":"https://openalex.org/C168563851","wikidata":"https://www.wikidata.org/wiki/Q1436668","display_name":"Randomized controlled trial","level":2,"score":0.6012771725654602},{"id":"https://openalex.org/C2781059491","wikidata":"https://www.wikidata.org/wiki/Q422232","display_name":"Methotrexate","level":2,"score":0.5894724130630493},{"id":"https://openalex.org/C44249647","wikidata":"https://www.wikidata.org/wiki/Q208498","display_name":"Confidence interval","level":2,"score":0.5874392986297607},{"id":"https://openalex.org/C156957248","wikidata":"https://www.wikidata.org/wiki/Q1862216","display_name":"Odds ratio","level":2,"score":0.5717411637306213},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.4774820804595947},{"id":"https://openalex.org/C2776694085","wikidata":"https://www.wikidata.org/wiki/Q974135","display_name":"Chemotherapy","level":2,"score":0.42258748412132263},{"id":"https://openalex.org/C535046627","wikidata":"https://www.wikidata.org/wiki/Q30612","display_name":"Clinical trial","level":2,"score":0.4197102189064026},{"id":"https://openalex.org/C90924648","wikidata":"https://www.wikidata.org/wiki/Q120569","display_name":"Gastroenterology","level":1,"score":0.35513341426849365},{"id":"https://openalex.org/C141071460","wikidata":"https://www.wikidata.org/wiki/Q40821","display_name":"Surgery","level":1,"score":0.3363170325756073}],"mesh":[{"descriptor_ui":"D000368","descriptor_name":"Aged","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000971","descriptor_name":"Antineoplastic Combined Chemotherapy Protocols","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D005260","descriptor_name":"Female","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005472","descriptor_name":"Fluorouracil","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":true},{"descriptor_ui":"D005472","descriptor_name":"Fluorouracil","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008113","descriptor_name":"Liver Neoplasms","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":false},{"descriptor_ui":"D008113","descriptor_name":"Liver Neoplasms","qualifier_ui":"Q000556","qualifier_name":"secondary","is_major_topic":false},{"descriptor_ui":"D008175","descriptor_name":"Lung Neoplasms","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":false},{"descriptor_ui":"D008175","descriptor_name":"Lung Neoplasms","qualifier_ui":"Q000556","qualifier_name":"secondary","is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008727","descriptor_name":"Methotrexate","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":true},{"descriptor_ui":"D008875","descriptor_name":"Middle Aged","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D012044","descriptor_name":"Regression Analysis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015179","descriptor_name":"Colorectal Neoplasms","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D015179","descriptor_name":"Colorectal Neoplasms","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":true},{"descriptor_ui":"D016019","descriptor_name":"Survival Analysis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016032","descriptor_name":"Randomized Controlled Trials as Topic","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":3,"locations":[{"id":"doi:10.1200/jco.1994.12.5.960","doi":"https://doi.org/10.1200/jco.1994.12.5.960","is_oa":false,"landing_page_url":"https://doi.org/10.1200/jco.1994.12.5.960","pdf_url":null,"source":{"id":"https://openalex.org/S15137598","display_name":"Journal of Clinical Oncology","issn_l":"0732-183X","issn":["0732-183X","1527-7755"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Clinical Oncology","raw_type":"journal-article"},{"id":"pmid:8164048","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/8164048","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of clinical oncology : official journal of the American Society of Clinical Oncology","raw_type":"Journal Article"},{"id":"mag:2460038169","doi":null,"is_oa":false,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0016694/","pdf_url":null,"source":{"id":"https://openalex.org/S15137598","display_name":"Journal of Clinical Oncology","issn_l":"0732-183X","issn":["0732-183X","1527-7755"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":"Journal of Clinical Oncology","raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[{"score":1.0,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[{"display_name":"Systematic Review","id":"https://openalex.org/study-designs/systematic-review"},{"display_name":"Meta-Analysis","id":"https://openalex.org/study-designs/meta-analysis"}],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":24,"referenced_works":["https://openalex.org/W1495571942","https://openalex.org/W1535441861","https://openalex.org/W1565550299","https://openalex.org/W1622475365","https://openalex.org/W1840238080","https://openalex.org/W1844072307","https://openalex.org/W1847455118","https://openalex.org/W1885154202","https://openalex.org/W1909566927","https://openalex.org/W1916504364","https://openalex.org/W1956445014","https://openalex.org/W1980735579","https://openalex.org/W2014203514","https://openalex.org/W2038252730","https://openalex.org/W2052318889","https://openalex.org/W2132039541","https://openalex.org/W2150000105","https://openalex.org/W2268624303","https://openalex.org/W2394722212","https://openalex.org/W2424533929","https://openalex.org/W2426305656","https://openalex.org/W2602544133","https://openalex.org/W2971417670","https://openalex.org/W2995133996"],"related_works":["https://openalex.org/W2030818307","https://openalex.org/W2071822872","https://openalex.org/W1947562604","https://openalex.org/W7097498410","https://openalex.org/W2602544133","https://openalex.org/W1844072307","https://openalex.org/W2460038169","https://openalex.org/W2464961141","https://openalex.org/W2100052454","https://openalex.org/W2413706907"],"abstract_inverted_index":{"PURPOSE:":[0],"Even":[1],"though":[2],"fluorouracil":[3],"(5FU)":[4],"remains":[5],"the":[6,41,50,67,208,250,265,272],"standard":[7],"treatment":[8,248],"of":[9,15,31,43,52,55,70,101,185,225,255,267],"advanced":[10],"colorectal":[11],"cancer,":[12],"almost":[13],"90%":[14],"patients":[16,56,103,144,163],"treated":[17],"with":[18,113,134,160,178,220],"5FU":[19,32,73,111,147,268],"alone":[20,112,148],"do":[21],"not":[22],"achieve":[23],"an":[24,37,128,179,221],"objective":[25],"response":[26,88,139,150,155,181,257,273],"to":[27,39,46,79,146,165,192,230,275],"chemotherapy.":[28],"Biochemical":[29],"modulation":[30,266],"by":[33,119,127,269],"methotrexate":[34],"(MTX)":[35],"is":[36,64,262],"attempt":[38],"increase":[40],"sensitivity":[42],"tumor":[44,87,256],"cells":[45],"5FU.":[47],"However,":[48],"despite":[49],"inclusion":[51],"several":[53],"hundreds":[54],"in":[57,105,207,282],"randomized":[58,107,247],"clinical":[59,68,108],"trials,":[60],"no":[61],"definitive":[62],"evidence":[63],"available":[65],"on":[66,98],"benefit":[69,82],"5FU/MTX":[71,166,211],"over":[72],"alone.":[74],"A":[75],"meta-analysis":[76,95],"was":[77,96,141,175,216],"performed":[78,126],"assess":[80],"this":[81],"objectively":[83],"and":[84,90,131,204,210,238,246,258,277],"quantitatively":[85],"for":[86,143,162],"rate":[89,140,274],"overall":[91,180,198,222],"survival.":[92,259,283],"DESIGN:":[93],"The":[94,123],"based":[97],"individual":[99],"data":[100,116],"1,178":[102],"included":[104],"eight":[106],"trials":[109],"comparing":[110],"5FU/MTX.":[114],"Patient":[115],"were":[117,125,201,249],"provided":[118],"all":[120,135],"principal":[121],"investigators.":[122],"analyses":[124],"independent":[129],"secretariat,":[130],"then":[132],"discussed":[133],"collaborators.":[136],"RESULTS:":[137],"Tumor":[138],"10%":[142],"allocated":[145,164],"(complete":[149],"[CR]":[151],"rate,":[152,157,168,171],"2%;":[153],"partial":[154],"[PR]":[156],"8%)":[158],"compared":[159],"19%":[161],"(CR":[167],"3%;":[169],"PR":[170],"16%).":[172],"This":[173,214],"difference":[174,215],"highly":[176],"significant,":[177,219],"odds":[182],"ratio":[183],"(OR)":[184],"0.51":[186],"(95%":[187,227],"confidence":[188],"interval":[189],"[CI],":[190],"0.37":[191],"0.70)":[193],"(P":[194,232],"<":[195],".0001).":[196],"Median":[197],"survival":[199,223],"times":[200],"9.1":[202],"months":[203,206],"10.7":[205],"5FU-alone":[209],"groups,":[212],"respectively.":[213],"also":[217],"statistically":[218],"OR":[224],"0.87":[226],"CI,":[228],"0.77":[229],"0.98)":[231],"=":[233],".024).":[234],"Logistic":[235],"regression":[236,240],"model":[237,241],"Cox":[239],"showed":[242],"that":[243,264],"performance":[244],"status":[245],"only":[251],"two":[252],"significant":[253],"predictors":[254],"CONCLUSION:":[260],"It":[261],"concluded":[263],"MTX":[270],"doubles":[271],"5FU,":[276],"yields":[278],"a":[279],"small":[280],"improvement":[281]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2025,"cited_by_count":2},{"year":2024,"cited_by_count":1},{"year":2023,"cited_by_count":1},{"year":2022,"cited_by_count":1},{"year":2021,"cited_by_count":2},{"year":2019,"cited_by_count":1},{"year":2018,"cited_by_count":1},{"year":2017,"cited_by_count":2},{"year":2016,"cited_by_count":1},{"year":2015,"cited_by_count":3},{"year":2014,"cited_by_count":3},{"year":2013,"cited_by_count":3},{"year":2012,"cited_by_count":2}],"updated_date":"2026-11-07T11:25:07.637180","created_date":"2022-05-12T00:00:00"}