{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T03:36:56Z","timestamp":1773113816353,"version":"3.50.1"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2012,3,14]],"date-time":"2012-03-14T00:00:00Z","timestamp":1331683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100007013","name":"F. Hoffmann-La Roche Ltd.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The goals of treatment for metastatic breast cancer (MBC) are to prolong overall survival (OS) while maximizing quality of life, palliating symptoms, and delaying tumor progression. For many years, anthracyclines and taxanes have been the mainstay of treatment for MBC, but these agents are now commonly administered earlier in the course of the disease. A recent meta-analysis revealed adverse effects on OS and overall response rates in patients with MBC receiving first-line anthracycline-based chemotherapy following relapse on adjuvant chemotherapy. Noncrossresistant cytotoxic agents and combinations that combine high clinical activity and acceptable tolerability while being convenient for patients are therefore needed for the first-line treatment of MBC patients. Capecitabine has substantial antitumor activity in the first-line treatment of patients with MBC in prospective, randomized, phase II\/III clinical trials as monotherapy and in combination with biologic and novel agents. First-line capecitabine monotherapy has a favorable safety profile, lacking myelosuppression and alopecia, and does not compromise the administration of further lines of chemotherapy. Capecitabine is suitable for long-term administration without the cumulative toxicity that can limit the prolonged use of other chemotherapy agents. Here, we review the available data on capecitabine as a single agent for first-line treatment of patients with human epidermal growth factor receptor 2\u2013negative MBC.<\/jats:p>","DOI":"10.1634\/theoncologist.2011-0281","type":"journal-article","created":{"date-parts":[[2012,3,15]],"date-time":"2012-03-15T07:04:15Z","timestamp":1331795055000},"page":"476-484","source":"Crossref","is-referenced-by-count":55,"title":["Capecitabine Monotherapy: Review of Studies in First-Line HER-2-Negative Metastatic Breast Cancer"],"prefix":"10.1093","volume":"17","author":[{"given":"Joyce A.","family":"O'Shaughnessy","sequence":"first","affiliation":[{"name":"a Baylor-Sammons Cancer Center, Texas Oncology, US Oncology, Dallas, Texas, USA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manfred","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"b University Hospital Frankfurt, Frankfurt, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Friederike","family":"Siedentopf","sequence":"additional","affiliation":[{"name":"c Praxis f\u00fcr Gyn\u00e4kologie Dr Schoenegg, Berlin, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Dalivoust","sequence":"additional","affiliation":[{"name":"d H\u00f4pital Ambroise Par\u00e9, Marseille, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Debled","sequence":"additional","affiliation":[{"name":"e Institut Bergoni\u00e9, South-West Comprehensive Cancer Center, Bordeaux Cedex, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas J.","family":"Robert","sequence":"additional","affiliation":[{"name":"f Virginia Cancer Specialists, US Oncology, Fairfax, Virginia, USA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia","family":"Harbeck","sequence":"additional","affiliation":[{"name":"g Breast Cancer, University Hospital of Cologne, Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2012,3,14]]},"reference":[{"key":"2021122308151095300_B1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1093\/annonc\/mdl155","article-title":"Second consensus on medical treatment of metastatic breast cancer","volume":"18","author":"Beslija","year":"2007","journal-title":"Ann Oncol"},{"issue":"suppl 1","key":"2021122308151095300_B2","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1634\/theoncologist.11-90001-42","article-title":"The role of capecitabine in first-line treatment for patients with metastatic breast cancer","volume":"11","author":"Gelmon","year":"2006","journal-title":"The Oncologist"},{"key":"2021122308151095300_B3","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1159\/000260904","article-title":"First-line capecitabine monotherapy for slowly progressing metastatic breast cancer: Do we need aggressive treatment?","volume":"77","author":"Debled","year":"2009","journal-title":"Oncology"},{"key":"2021122308151095300_B4","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1093\/oxfordjournals.jncimonographs.a003469","article-title":"Preoperative chemotherapy in patients with operable breast cancer: Nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18","volume":"30","author":"Wolmark","year":"2001","journal-title":"J Natl Cancer Inst Monogr"},{"key":"2021122308151095300_B5","doi-asserted-by":"crossref","first-page":"4165","DOI":"10.1200\/JCO.2003.12.005","article-title":"The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: Preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27","volume":"21","author":"Bear","year":"2003","journal-title":"J Clin Oncol"},{"key":"2021122308151095300_B6","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/S0140-6736(98)03301-7","article-title":"Polychemotherapy for early breast cancer: An overview of the randomised trials","volume":"352","author":"Early Breast Cancer Trialists' Collaborative Group","year":"1998","journal-title":"Lancet"},{"key":"2021122308151095300_B7","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1200\/JCO.2007.11.3787","article-title":"Taxane-based combinations as adjuvant chemotherapy of early breast cancer: A meta-analysis of randomized trials","volume":"26","author":"De Laurentiis","year":"2008","journal-title":"J Clin Oncol"},{"key":"2021122308151095300_B8","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1093\/annonc\/mdp322","article-title":"Thresholds for therapies: Highlights of the St Gallen international Expert Consensus on the primary therapy of early breast cancer 2009","volume":"20","author":"Goldhirsch","year":"2009","journal-title":"Ann Oncol"},{"key":"2021122308151095300_B9","article-title":"Clinical Practice Guidelines in Oncology","volume-title":"Breast Cancer Screening and Diagnosis, v. 1.2010","author":"National Comprehensive Cancer Network (NCCN)"},{"key":"2021122308151095300_B10","volume-title":"AGO Guidelines","author":"Arbeitsgemeinschaft Gyn\u00e4kologische Onkologie (AGO)"},{"key":"2021122308151095300_B11","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1016\/S0959-8049(98)00058-6","article-title":"Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue","volume":"34","author":"Miwa","year":"1998","journal-title":"Eur J Cancer"},{"key":"2021122308151095300_B12","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.clbc.2011.06.005","article-title":"Dose-adjusting capecitabine minimizes side effects while maintaining efficacy: A retrospective review of capecitabine for metastatic breast cancer","volume":"11","author":"Leonard","year":"2011","journal-title":"Clin Breast Cancer"},{"key":"2021122308151095300_B13","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/j.1365-2354.2008.00999.x","article-title":"Oral treatment of metastatic breast cancer with capecitabine: What influences the decision-making process?","volume":"19","author":"G\u00f3rna\u015b","year":"2010","journal-title":"Eur J Cancer Care"},{"key":"2021122308151095300_B14","doi-asserted-by":"crossref","first-page":"2733","DOI":"10.1056\/NEJMoa064320","article-title":"Lapatinib plus capecitabine for HER2-positive advanced breast cancer","volume":"355","author":"Geyer","year":"2006","journal-title":"N Engl J Med"},{"key":"2021122308151095300_B15","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1007\/s10549-007-9885-0","article-title":"A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: Updated efficacy and biomarker analyses","volume":"112","author":"Cameron","year":"2008","journal-title":"Breast Cancer Res Treat"},{"key":"2021122308151095300_B16","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1200\/JCO.2008.19.6618","article-title":"Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: A German Breast Group 26\/Breast International Group 03\u201305 study","volume":"27","author":"Minckwitz","year":"2009","journal-title":"J Clin Oncol"},{"key":"2021122308151095300_B17","doi-asserted-by":"crossref","first-page":"4498","DOI":"10.1200\/JCO.2010.33.9101","article-title":"Capecitabine versus classical cyclophosphamide, methotrexate, and fluorouracil as first-line chemotherapy for advanced breast cancer","volume":"29","author":"Stockler","year":"2011","journal-title":"J Clin Oncol"},{"issue":"15 suppl","key":"2021122308151095300_B18","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1200\/jco.2010.28.15_suppl.1022","article-title":"A randomized phase III study evaluating pegylated liposomal doxorubicin (PLD) versus capecitabine (CAP) as first-line therapy for metastatic breast cancer (MBC): Results of the PELICAN study","volume":"28","author":"J\u00e4ger","year":"2010","journal-title":"J Clin Oncol"},{"key":"2021122308151095300_B19","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1200\/JCO.2010.28.0982","article-title":"RIBBON-1: Randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer","volume":"29","author":"Robert","year":"2011","journal-title":"J Clin Oncol"},{"issue":"suppl 2","key":"2021122308151095300_B20","doi-asserted-by":"crossref","first-page":"6117","DOI":"10.1158\/0008-5472.SABCS-6117","article-title":"Ixabepilone plus capecitabine vs capecitabine in patients with metastatic breast cancer receiving ixabepilone in the first line setting: A pooled analysis from two phase III studies","volume":"69","author":"Vahdat","year":"2009","journal-title":"Cancer Res"},{"key":"2021122308151095300_B21","doi-asserted-by":"crossref","first-page":"3184","DOI":"10.1016\/j.ejca.2010.07.009","article-title":"First-line therapy with moderate dose capecitabine in metastatic breast cancer is safe and active: Results of the MONICA trial","volume":"46","author":"Kaufmann","year":"2010","journal-title":"Eur J Cancer"},{"key":"2021122308151095300_B22","doi-asserted-by":"crossref","first-page":"3LBA","DOI":"10.1016\/S1359-6349(09)72031-2","article-title":"SOLTI-0701: A double-blind, randomized phase 2b study evaluating the efficacy and safety of sorafenib (SOR) compared to placebo (PL) when administered in combination with capecitabine (CAP) in patients (pts) with locally advanced (adv) or metastatic breast cancer [abstract 3]","volume":"7","author":"Baselga","year":"2009","journal-title":"Eur J Cancer Suppl"},{"issue":"suppl 3","key":"2021122308151095300_B23","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1158\/0008-5472.SABCS-09-45","article-title":"SOLTI-0701: A multinational, double-blind, randomized phase 2b study evaluating the efficacy and safety of sorafenib compared to placebo in combination with capecitabine in patients with locally advanced or metastatic breast cancer","volume":"69","author":"Baselga","year":"2009","journal-title":"Cancer Res"},{"key":"2021122308151095300_B24","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1023\/A:1012281104865","article-title":"Randomized, open-label, phase II trial of oral capecitabine (Xeloda\u00ae) vs. a reference arm of intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) as first-line therapy for advanced\/metastatic breast cancer","volume":"12","author":"O'Shaughnessy","year":"2001","journal-title":"Ann Oncol"},{"key":"2021122308151095300_B25","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s00280-001-0401-7","article-title":"Antitumor activity of combinations of anti-HER-2 antibody trastuzumab and oral fluoropyrimidines capecitabine\/5\u2032-dFUrd in human breast cancer models","volume":"49","author":"Fujimoto-Ouchi","year":"2002","journal-title":"Cancer Chemother Pharmacol"},{"key":"2021122308151095300_B26","first-page":"2279","article-title":"Antitumour activity of capecitabine and bevacizumab combination in a human estrogen receptor-negative breast adenocarcinoma xenograft model","volume":"27","author":"Higgins","year":"2007","journal-title":"Anticancer Res"},{"issue":"15 suppl","key":"2021122308151095300_B27","doi-asserted-by":"crossref","first-page":"TPS131","DOI":"10.1200\/jco.2010.28.15_suppl.tps131","article-title":"Phase II, two-arm, double-blind, multicenter, randomized study of the combination of oral WX-671 plus capecitabine versus capecitabine in first-line HER2-negative metastatic breast cancer (MBC)","volume":"28","author":"Goldstein","year":"2010","journal-title":"J Clin Oncol"},{"key":"2021122308151095300_B28","doi-asserted-by":"crossref","first-page":"5210","DOI":"10.1200\/JCO.2007.12.6557","article-title":"Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracyclines and taxane treatment","volume":"25","author":"Thomas","year":"2007","journal-title":"J Clin Oncol"},{"key":"2021122308151095300_B29","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s10549-010-0901-4","article-title":"Analysis of overall survival from a phase III study of ixabepilone plus capecitabine versus capecitabine in patients with MBC resistant to anthracyclines and taxanes","volume":"122","author":"Hortobagyi","year":"2010","journal-title":"Breast Cancer Res Treat"},{"key":"2021122308151095300_B30","volume-title":"Analysis of overall survival (OS) among patients (pts) with metastatic breast cancer (MBC) receiving either Ixabepilone (I) plus capecitabine I or C alone: Results from two randomized phase III trials [abstract 186]","author":"Hortobagyi","year":"2008"},{"key":"2021122308151095300_B31","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1159\/000242219","article-title":"Capecitabine in the routine treatment of advanced breast cancer: Results from a non-interventional observational study in 876 patients","volume":"32","author":"Siedentopf","year":"2009","journal-title":"Onkologie"},{"issue":"suppl 24","key":"2021122308151095300_B32","doi-asserted-by":"crossref","first-page":"P6-11-04","DOI":"10.1158\/0008-5472.SABCS10-P6-11-04","article-title":"Capecitabine therapy for locally advanced or metastatic breast cancer: A difference between reported clinical trials and routine clinical practice? Results from the ELIXIR study in routine oncology practice","volume":"70","author":"Dalivoust","year":"2010","journal-title":"Cancer Res"},{"key":"2021122308151095300_B33","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.critrevonc.2010.10.002","article-title":"First-line chemotherapy for metastatic breast cancer in patients \u226575 years: A retrospective single-centre analysis","volume":"80","author":"Debled","year":"2011","journal-title":"Crit Rev Oncol Hematol"},{"key":"2021122308151095300_B34","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1093\/annonc\/mdi181","article-title":"First-line gemcitabine versus epirubicin in postmenopausal women aged 60 or older with metastatic breast cancer: A multicenter, randomized, phase III study","volume":"16","author":"Feher","year":"2005","journal-title":"Ann Oncol"},{"key":"2021122308151095300_B35","doi-asserted-by":"crossref","first-page":"3415","DOI":"10.1200\/JCO.2006.09.7535","article-title":"Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, as first-line therapy in patients with metastatic breast cancer previously treated with anthracycline chemotherapy","volume":"25","author":"Roch\u00e9","year":"2007","journal-title":"J Clin Oncol"},{"key":"2021122308151095300_B36","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1200\/JCO.1993.11.7.1245","article-title":"Phase II trial of weekly intravenous vinorelbine in first-line advanced breast cancer chemotherapy","volume":"11","author":"Fumoleau","year":"1993","journal-title":"J Clin Oncol"},{"key":"2021122308151095300_B37","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1097\/00000421-199510000-00006","article-title":"Phase II trial of weekly i.v. vinorelbine as a single agent in first-line advanced breast cancer chemotherapy. The Latin-American experience","volume":"18","author":"Bruno","year":"1995","journal-title":"Am J Clin Oncol"},{"key":"2021122308151095300_B38","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.ejon.2007.10.002","article-title":"The impact of cancer and chemotherapy: Perceptual similarities and differences between cancer patients, nurses and physicians","volume":"12","author":"Mulders","year":"2008","journal-title":"Eur J Oncol Nurs"},{"key":"2021122308151095300_B39","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1002\/pon.1245","article-title":"Chemotherapy-induced alopecia and effects on quality of life among women with breast cancer: A literature review","volume":"17","author":"Lemieux","year":"2008","journal-title":"Psychooncology"},{"key":"2021122308151095300_B40","doi-asserted-by":"crossref","first-page":"4125","DOI":"10.1002\/cncr.25992","article-title":"Phase 2 trial of a novel capecitabine dosing schedule in combination with bevacizumab for patients with metastatic breast cancer","volume":"117","author":"Gajria","year":"2011","journal-title":"Cancer"},{"key":"2021122308151095300_B41","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s10549-011-1749-y","article-title":"Phase II trial of a novel capecitabine dosing schedule in combination with lapatinib for the treatment of patients with HER2-positive metastatic breast cancer","volume":"131","author":"Gajria","year":"2012","journal-title":"Breast Cancer Res Treat"},{"key":"2021122308151095300_B42","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s12282-009-0137-5","article-title":"Phase II study of 4-weekly capecitabine monotherapy in advanced\/metastatic breast cancer","volume":"17","author":"Kusama","year":"2010","journal-title":"Breast Cancer"},{"key":"2021122308151095300_B43","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1159\/000313531","article-title":"Study of low-dose capecitabine for metastatic breast cancer","volume":"56","author":"Taguchi","year":"2010","journal-title":"Chemotherapy"},{"issue":"15 suppl","key":"2021122308151095300_B44","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1200\/jco.2011.29.15_suppl.1008","article-title":"Randomized, phase II trial comparing continuous vs intermittent capecitabine (X) monotherapy for metastatic breast cancer (MBC): Results from the GEICAM 2009\u201305 study","volume":"29","author":"Mart\u00edn","year":"2011","journal-title":"J Clin Oncol"},{"key":"2021122308151095300_B45","first-page":"1079","article-title":"Capecitabine after anthracycline and taxane exposure in HER2-negative metastatic breast cancer patients: Response, survival and prognostic factors","volume":"31","author":"Gilabert","year":"2011","journal-title":"Anticancer Res"},{"key":"2021122308151095300_B46","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/S1470-2045(09)70307-9","article-title":"Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for breast cancer: An open-label, randomised controlled trial","volume":"10","author":"Joensuu","year":"2009","journal-title":"Lancet Oncol"},{"issue":"suppl 24","key":"2021122308151095300_B47","first-page":"S4","article-title":"First efficacy results of a randomized, open-label, phase III study of adjuvant doxorubicin plus cyclophosphamide followed by docetaxel with or without capecitabine in high-risk early breast cancer","volume":"70","author":"O'Shaughnessy","year":"2010","journal-title":"Cancer Res"},{"issue":"8 suppl","key":"2021122308151095300_B48","article-title":"Evolution of chemotherapy options in HER2-negative metastatic breast cancer (MBC)","volume":"21","author":"Verma","year":"2010","journal-title":"Ann Oncol"}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pericles-gcp.literatumonline.com\/doi\/pdf\/10.1634\/theoncologist.2011-0281","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pericles-gcp.literatumonline.com\/doi\/full-xml\/10.1634\/theoncologist.2011-0281","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/17\/4\/476\/41858818\/oncolo_17_4_476.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/17\/4\/476\/41858818\/oncolo_17_4_476.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T04:25:34Z","timestamp":1687321534000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/17\/4\/476\/6445240"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,3,14]]},"references-count":48,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2012,3,14]]},"published-print":{"date-parts":[[2012,4,1]]}},"URL":"https:\/\/doi.org\/10.1634\/theoncologist.2011-0281","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"value":"1083-7159","type":"print"},{"value":"1549-490X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2012,4,1]]},"published":{"date-parts":[[2012,3,14]]}}}