{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T22:45:16Z","timestamp":1761864316826,"version":"build-2065373602"},"reference-count":26,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100002429","name":"Amgen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002429","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006010","name":"Bayer HealthCare Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007075","name":"European Society for Medical Oncology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007075","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinical-colorectal-cancer.com","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Clinical Colorectal Cancer"],"published-print":{"date-parts":[[2021,12]]},"DOI":"10.1016\/j.clcc.2021.07.006","type":"journal-article","created":{"date-parts":[[2021,7,24]],"date-time":"2021-07-24T19:23:08Z","timestamp":1627154588000},"page":"326-333","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"title":["Sex and Regorafenib Toxicity in Refractory Colorectal Cancer: Safety Analysis of the RegARd-C Trial"],"prefix":"10.1016","volume":"20","author":[{"given":"Caroline","family":"Vandeputte","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giacomo","family":"Bregni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paraskevas","family":"Gkolfakis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7041-598X","authenticated-orcid":false,"given":"Thomas","family":"Guiot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0262-9270","authenticated-orcid":false,"given":"Andrea","family":"Pretta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pashalina","family":"Kehagias","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Senti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena Acedo","family":"Reina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camille","family":"Van Bogaert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Am\u00e9lie","family":"Deleporte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Geboes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thierry","family":"Delaunoit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gauthier","family":"Demolin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Peeters","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lionel","family":"D'Hondt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos","family":"Janssens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Carrasco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephane","family":"Holbrechts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Charles","family":"Goeminne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Vergauwe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Luc","family":"Van Laethem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Flamen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alain","family":"Hendlisz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Sclafani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.clcc.2021.07.006_bib0001","first-page":"7","article-title":"Cancer statistics 2019","volume":"69","author":"Siegel","year":"2019","journal-title":"CA Cancer J Clin"},{"key":"10.1016\/j.clcc.2021.07.006_bib0002","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1007\/s11912-011-0157-0","article-title":"Curable metastatic colorectal cancer","volume":"13","author":"Eadens","year":"2011","journal-title":"Curr Oncol Rep"},{"key":"10.1016\/j.clcc.2021.07.006_bib0003","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1038\/bjc.2013.94","article-title":"The beneficial effect of palliative resection in metastatic colorectal cancer","volume":"108","author":"Park","year":"2013","journal-title":"Br J Cancer"},{"key":"10.1016\/j.clcc.2021.07.006_bib0004","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1093\/annonc\/mdw235","article-title":"ESMO consensus guidelines for the management of patients with metastatic colorectal cancer","volume":"27","author":"Van Cutsem","year":"2016","journal-title":"Ann Oncol"},{"key":"10.1016\/j.clcc.2021.07.006_bib0005","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S0140-6736(12)61900-X","article-title":"Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial","volume":"381","author":"Grothey","year":"2013","journal-title":"Lancet"},{"key":"10.1016\/j.clcc.2021.07.006_bib0006","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1056\/NEJMoa1414325","article-title":"Randomized trial of TAS-102 for refractory metastatic colorectal cancer","volume":"372","author":"Mayer","year":"2015","journal-title":"N Engl J Med"},{"key":"10.1016\/j.clcc.2021.07.006_bib0007","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1001\/jama.2018.7855","article-title":"Effect of fruquintinib vs placebo on overall survival in patients with previously treated metastatic colorectal cancer: the FRESCO randomized clinical trial","volume":"319","author":"Li","year":"2018","journal-title":"JAMA"},{"key":"10.1016\/j.clcc.2021.07.006_bib0008","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-019-0308-1","article-title":"Anti-tumoral activity of single and combined regorafenib treatments in preclinical models of liver and gastrointestinal cancers","volume":"51","author":"Fondevila","year":"2019","journal-title":"Exp Mol Med"},{"key":"10.1016\/j.clcc.2021.07.006_bib0009","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/S1470-2045(15)70156-7","article-title":"Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"16","author":"Li","year":"2015","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.clcc.2021.07.006_bib0010","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1634\/theoncologist.2018-0072","article-title":"Regorafenib for patients with metastatic colorectal cancer who progressed after standard therapy: results of the large, single-arm, open-label phase IIIb CONSIGN study","volume":"24","author":"Van Cutsem","year":"2019","journal-title":"Oncologist"},{"key":"10.1016\/j.clcc.2021.07.006_bib0011","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.ejca.2019.09.015","article-title":"Safety and effectiveness of regorafenib in patients with metastatic colorectal cancer in routine clinical practice in the prospective, observational CORRELATE study","volume":"123","author":"Ducreux","year":"2019","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.clcc.2021.07.006_bib0012","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1016\/S1470-2045(19)30272-4","article-title":"Regorafenib dose-optimisation in patients with refractory metastatic colorectal cancer (ReDOS): a randomised, multicentre, open-label, phase 2 study","volume":"20","author":"Bekaii-Saab","year":"2019","journal-title":"Lancet Oncol"},{"issue":"suppl 4","key":"10.1016\/j.clcc.2021.07.006_bib0013","article-title":"Results of REARRANGE trial: a randomized phase 2 study comparing different dosing approaches for regorafenib (REG) during the first cycle of treatment in patients (pts) with metastatic colorectal cancer (mCRC)","volume":"30","author":"Argiles","year":"2019","journal-title":"Ann Oncol"},{"issue":"suppl 4","key":"10.1016\/j.clcc.2021.07.006_bib0014","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1200\/JCO.2018.36.4_suppl.821","article-title":"Phase II dose titration study of regorafenib for patients with unresectable metastatic colorectal cancer that progressed after standard chemotherapy","volume":"36","author":"Kudo","year":"2018","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.clcc.2021.07.006_bib0015","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2014-007189","article-title":"Regorafenib assessment in refractory advanced colorectal cancer: RegARd-C study protocol","volume":"5","author":"Hendlisz","year":"2015","journal-title":"BMJ Open"},{"key":"10.1016\/j.clcc.2021.07.006_bib0016","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1139\/H08-075","article-title":"A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care","volume":"33","author":"Mourtzakis","year":"2008","journal-title":"Appl Physiol Nutr Metab"},{"unstructured":"National Comprehensive Cancer Network. Colon Cancer (Version 2.2021). Available at: http:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/colon.pdf. Accessed: February 1, 2021.","key":"10.1016\/j.clcc.2021.07.006_bib0017"},{"key":"10.1016\/j.clcc.2021.07.006_bib0018","doi-asserted-by":"crossref","first-page":"2680","DOI":"10.1200\/JCO.2018.78.3290","article-title":"Sex differences in efficacy and toxicity of systemic treatments: an undervalued issue in the era of precision oncology","volume":"36","author":"\u00d6zdemir","year":"2018","journal-title":"J Clin Oncol"},{"issue":"suppl 15","key":"10.1016\/j.clcc.2021.07.006_bib0019","doi-asserted-by":"crossref","first-page":"4109","DOI":"10.1200\/JCO.2019.37.15_suppl.4109","article-title":"Impact of gender on multikinase inhibitors (MKIs) toxicity in patients (pts) with advanced pancreatic and gastrointestinal neuroendocrine tumors (NETs): A pooled analysis of two phase II trials with pazopanib and lenvatinib","volume":"37","author":"Hernando-Cubero","year":"2019","journal-title":"J Clin Oncol"},{"issue":"suppl 9","key":"10.1016\/j.clcc.2021.07.006_bib0020","article-title":"Phase 3 correct trial of regorafenib in metastatic colorectal cancer (MCRC): overall survival update","volume":"23","author":"Van Cutsem","year":"2012","journal-title":"Ann Oncol"},{"key":"10.1016\/j.clcc.2021.07.006_bib0021","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.2147\/PPA.S217835","article-title":"Factors associated with regorafenib adherence with metastatic colorectal cancer","volume":"13","author":"Kawakami","year":"2019","journal-title":"Patient Prefer Adherence"},{"key":"10.1016\/j.clcc.2021.07.006_bib0022","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1093\/annonc\/mdz414","article-title":"Gender medicine and oncology: report and consensus of an ESMO workshop","volume":"30","author":"Wagner","year":"2019","journal-title":"Ann Oncol"},{"unstructured":"CHMP, extension of indication variation assessment report \u2013 Stivarga. 2014. Available at: https:\/\/www.ema.europa.eu\/en\/documents\/variation-report\/stivarga-h-c-2573-ii-0001-epar-assessment-report-variation_en.pdf. Accessed: February 1, 2021.","key":"10.1016\/j.clcc.2021.07.006_bib0023"},{"issue":"suppl 8","key":"10.1016\/j.clcc.2021.07.006_bib0024","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1158\/1538-7445.AM10-1666","article-title":"Regorafenib (BAY 73-4506): preclinical pharmacology and clinical identification and quantification of its major metabolites","volume":"70","author":"Zopf","year":"2010","journal-title":"Cancer Res"},{"key":"10.1016\/j.clcc.2021.07.006_bib0025","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s10147-019-01593-w","article-title":"Therapeutic drug monitoring of regorafenib and its metabolite M5 can predict treatment efficacy and the occurrence of skin toxicities","volume":"25","author":"Taguchi","year":"2020","journal-title":"Int J Clin Oncol"},{"key":"10.1016\/j.clcc.2021.07.006_bib0026","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1002\/hep.1840380424","article-title":"Sex is a major determinant of CYP3A4 expression in human liver","volume":"38","author":"Wolbold","year":"2003","journal-title":"Hepatology"}],"container-title":["Clinical Colorectal Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1533002821000712?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1533002821000712?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T23:07:53Z","timestamp":1761520073000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1533002821000712"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12]]},"references-count":26,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["S1533002821000712"],"URL":"https:\/\/doi.org\/10.1016\/j.clcc.2021.07.006","relation":{},"ISSN":["1533-0028"],"issn-type":[{"type":"print","value":"1533-0028"}],"subject":[],"published":{"date-parts":[[2021,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Sex and Regorafenib Toxicity in Refractory Colorectal Cancer: Safety Analysis of the RegARd-C Trial","name":"articletitle","label":"Article Title"},{"value":"Clinical Colorectal Cancer","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.clcc.2021.07.006","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}