{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:10:04Z","timestamp":1790298604839,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2017,5,10]],"date-time":"2017-05-10T00:00:00Z","timestamp":1494374400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U10CA180821"],"award-info":[{"award-number":["U10CA180821"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U10CA180882"],"award-info":[{"award-number":["U10CA180882"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U10CA180790"],"award-info":[{"award-number":["U10CA180790"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UG1CA189863"],"award-info":[{"award-number":["UG1CA189863"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U10CA025224"],"award-info":[{"award-number":["U10CA025224"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U10CA031946"],"award-info":[{"award-number":["U10CA031946"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U10CA033601"],"award-info":[{"award-number":["U10CA033601"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2017,9,15]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Oxaliplatin in combination with either 5\u2010fluorouracil or capecitabine is commonly used as first\u2010line therapy for patients with small bowel adenocarcinoma. The addition of irinotecan improves survival in other gastrointestinal tumors but at the cost of hematologic toxicity. The authors performed a phase 2 cooperative group study (North Central Cancer Treatment Group N0543, Alliance) using genotype\u2010dosed capecitabine, irinotecan, and oxaliplatin (gCAPIRINOX), with dosing assigned based on UDP glucuronosyltransferase family 1 member A1 (<jats:italic>UGT1A1<\/jats:italic>) genotype to test: 1) whether the addition of irinotecan would improve outcomes; and 2) whether <jats:italic>UGT1A1<\/jats:italic> genotype\u2010based dosing could optimize tolerability.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Previously untreated patients with advanced small bowel adenocarcinoma received irinotecan (day 1), oxaliplatin (day 1), and capecitabine (days 2\u201015) in a 21\u2010day cycle and were dosed with gCAPIRINOX according to <jats:italic>UGT1A1*28<\/jats:italic> genotypes (6\/6, 6\/7, and 7\/7).<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>A total of 33 patients (17 with the 6\/6 genotype, 10 with the 6\/7 genotype, and 6 with the 7\/7 genotype) were enrolled from October 2007 to November 2013; 73% were male, with a mean age of 64 years (range, 41\u201077 years). Location of the primary tumor included the duodenum (58%), jejunum (30%), and ileum (9%). The regimen yielded a confirmed response rate of 37.5% (95% confidence interval, 21%\u201056%), with a median progression\u2010free survival of 8.9 months and a median overall survival of 13.4 months. Neither hematologic toxicity (grade \u22653 in 52.9%, 30.0%, and 33.3%, respectively, of the 6\/6, 6\/7, and 7\/7 genotype groups) nor tumor response rate (41.2%, 33%, and 33%, respectively) were found to differ significantly by <jats:italic>UGT1A1<\/jats:italic> genotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p><jats:italic>UGT1A1<\/jats:italic> genotype\u2010directed dosing (gCAPIRINOX) appears to be feasible with favorable rates of hematologic toxicity compared with prior 3\u2010drug studies in unselected patients. Larger studies would be needed to determine the regimen's comparability to oxaliplatin and capecitabine (CapeOx) alone or if response\/toxicity differs among patients with different <jats:italic>UGT1A1<\/jats:italic> genotypes. <jats:bold><jats:italic>Cancer<\/jats:italic> 2017;123:3494\u2010501.<\/jats:bold> \u00a9 <jats:italic>2017 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.30766","type":"journal-article","created":{"date-parts":[[2017,5,10]],"date-time":"2017-05-10T12:34:37Z","timestamp":1494419677000},"page":"3494-3501","source":"Crossref","is-referenced-by-count":36,"title":["North Central Cancer Treatment Group N0543 (Alliance): A phase 2 trial of pharmacogenetic\u2010based dosing of irinotecan, oxaliplatin, and capecitabine as first\u2010line therapy for patients with advanced small bowel adenocarcinoma"],"prefix":"10.1002","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8199-5040","authenticated-orcid":false,"given":"Robert R.","family":"McWilliams","sequence":"first","affiliation":[{"name":"Division of Medical Oncology Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan R.","family":"Foster","sequence":"additional","affiliation":[{"name":"Alliance Statistics and Data Center Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle R.","family":"Mahoney","sequence":"additional","affiliation":[{"name":"Alliance Statistics and Data Center Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas C.","family":"Smyrk","sequence":"additional","affiliation":[{"name":"Division of Anatomic Pathology Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A.","family":"Murray","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew M.","family":"Ames","sequence":"additional","affiliation":[{"name":"Division of Pharmacology Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. Elise","family":"Horvath","sequence":"additional","affiliation":[{"name":"Alliance for Clinical Trials in Oncology Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Metro\u2010Minnesota Community Oncology Research Consortium Saint Paul Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Hobday","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1081-189X","authenticated-orcid":false,"given":"Aminah","family":"Jatoi","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey P.","family":"Meyers","sequence":"additional","affiliation":[{"name":"Alliance Statistics and Data Center Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P.","family":"Goetz","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,5,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.10-2-132"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.19.7145"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-8-148"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.09.046"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0b013e328350dd0d"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.01.238"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3816\/CCC.2007.n.017"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1011923"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00122-9"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.09.0928"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1403108"},{"key":"e_1_2_8_13_1","first-page":"6921","article-title":"Polymorphisms of UDP\u2010glucuronosyltransferase gene and irinotecan toxicity: a pharmacogenetic analysis","volume":"60","author":"Ando Y","year":"2000","journal-title":"Cancer Res."},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI915"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.07.173"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-1012"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.55.2307"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.23.6125"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-8981(97)00167-8"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2011.206"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-013-0034-9"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-2456(00)00115-X"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1958.10501452"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.4065\/72.4.320"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdh470"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clon.2008.02.011"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1500596"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8484122"},{"key":"e_1_2_8_29_1","first-page":"5849","article-title":"Genomic instability in colorectal cancer: relationship to clinicopathological variables and family history","volume":"53","author":"Lothe RA","year":"1993","journal-title":"Cancer Res."},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdu275"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dju106"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2013.677"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-1096"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2014.10.027"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.30766","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.30766","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T16:07:06Z","timestamp":1760285226000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.30766"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,10]]},"references-count":33,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2017,9,15]]}},"alternative-id":["10.1002\/cncr.30766"],"URL":"https:\/\/doi.org\/10.1002\/cncr.30766","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,10]]}}}