{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:58:12Z","timestamp":1760317092723,"version":"build-2065373602"},"reference-count":22,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T00:00:00Z","timestamp":1608595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>TAS\u2010102, a novel antimetabolite, is approved for treatment of refractory metastatic colorectal cancer (CRC). This study sought to determine whether the addition of TAS\u2010102 to oxaliplatin (TAS\u2010OX) was safe and effective in metastatic CRC previously treated with oxaliplatin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This investigator\u2010initiated, open\u2010label, single\u2010arm phase 1b study enrolled patients with metastatic CRC previously treated with 5\u2010fluorouracil, irinotecan, and oxaliplatin. In dose escalation, TAS\u2010102 was given at 3 dose levels: 25, 30, and 35 mg\/m<jats:sup>2<\/jats:sup> twice daily on day 1 to day 5 with 85 mg\/m<jats:sup>2<\/jats:sup> oxaliplatin on day 1 in 14\u2010day cycles. The primary endpoint of dose escalation was the recommended dose for expansion, and in dose expansion, the primary endpoint was overall response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Forty\u2010one patients were treated with TAS\u2010OX. No dose\u2010limiting toxicities were observed in the 11 patients treated in escalation. The recommended dose for expansion was 35 mg\/m<jats:sup>2<\/jats:sup> TAS\u2010102 twice daily on day 1 to day 5 in combination with 85 mg\/m<jats:sup>2<\/jats:sup> oxaliplatin on day 1 in 14\u2010day cycles. In the intention\u2010to\u2010treat population, the ORR was 2.4% (95% CI, 0%\u201012.9%) with 1 of 41 patients having a partial response, although 12 (29%) had tumor shrinkage. The median progression\u2010free survival was 2.7 months (95% CI, 2.4\u20104.8 months) and median overall survival was 6.8 months (95% CI, 5.7\u201010 months).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>TAS\u2010OX is safe with no unexpected toxicities at standard doses of each agent. The combination did not result in a clinically meaningful ORR, although progression\u2010free survival and overall survival were encouraging in this heavily pretreated population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Lay Summary<\/jats:title><jats:p>\n<jats:list list-type=\"bullet\">\n\n<jats:list-item><jats:p>For metastatic colorectal cancer, the treatment combination of TAS\u2010102 and oxaliplatin was found to be well\u2010tolerated and revealed no unexpected side effects.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>Twelve of 41 patients had reductions in the size of their tumor, and the study treatment delayed the time to tumor growth as opposed to what would be expected.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.33379","type":"journal-article","created":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T23:18:43Z","timestamp":1608679123000},"page":"1417-1424","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A phase 1b expansion study of TAS\u2010102 with oxaliplatin for refractory metastatic colorectal cancer"],"prefix":"10.1002","volume":"127","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3504-0128","authenticated-orcid":false,"given":"Michael","family":"Cecchini","sequence":"first","affiliation":[{"name":"Department of Internal Medicine (Medical Oncology) Yale University School of Medicine New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy S.","family":"Kortmansky","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Medical Oncology) Yale University School of Medicine New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Can","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Yale School of Public Health New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Yale School of Public Health New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaykumar Ranchobdhai","family":"Thumar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Medical Oncology) Yale University School of Medicine New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nataliya V.","family":"Uboha","sequence":"additional","affiliation":[{"name":"Hematology\u2010Oncology Section Department of Medicine University of Wisconsin Carbone Cancer Center Madison Wisconsin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Navid","family":"Hafez","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Medical Oncology) Yale University School of Medicine New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill","family":"Lacy","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Medical Oncology) Yale University School of Medicine New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neal A.","family":"Fischbach","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Medical Oncology) Yale University School of Medicine New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kert D.","family":"Sabbath","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Medical Oncology) Yale University School of Medicine New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina M.","family":"Gomez","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Medical Oncology) Yale University School of Medicine New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan Reed","family":"Sporn","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Medical Oncology) Yale University School of Medicine New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stacey","family":"Stein","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Medical Oncology) Yale University School of Medicine New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard S.","family":"Hochster","sequence":"additional","affiliation":[{"name":"Rutgers Cancer Institute of New Jersey New Brunswick New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,12,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21590"},{"key":"e_1_2_8_3_1","unstructured":"World Health Organization International Agency for Research on Cancer.GLOBOCAN 2018: estimated cancer incidence mortality and prevalence worldwide in 2018. Published February2019. Accessed April 18 2020.http:\/\/gco.iarc.fr\/today\/data\/factsheets\/cancers\/10_"},{"key":"e_1_2_8_4_1","unstructured":"National Comprehensive Cancer Network.NCCN clinical practice guidelines in oncology for colon cancer. Version 3. Accessed December 7 2020.https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/colon.pdf"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.23.4344"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdu107"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/COC.0b013e31823fe40e"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2007.00477.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1414325"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-2743"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30827-7"},{"key":"e_1_2_8_12_1","first-page":"4605","article-title":"Efficacy of combination chemotherapy using a novel oral chemotherapeutic agent, TAS\u2010102, with oxaliplatin on human colorectal and gastric cancer xenografts","volume":"35","author":"Nukatsuka M","year":"2015","journal-title":"Anticancer Res"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6603549"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2019.01.101"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-019-00749-9"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(11)70199-1"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02034-1"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.05.113"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.11.126"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.03.119"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdn370"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61900-X"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-016-2491-y"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.33379","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cncr.33379","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.33379","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T21:17:35Z","timestamp":1760303855000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.33379"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,22]]},"references-count":22,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["10.1002\/cncr.33379"],"URL":"https:\/\/doi.org\/10.1002\/cncr.33379","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"type":"print","value":"0008-543X"},{"type":"electronic","value":"1097-0142"}],"subject":[],"published":{"date-parts":[[2020,12,22]]},"assertion":[{"value":"2020-08-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}