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Ixabepilone plus capecitabine is currently approved for patients with locally advanced or metastatic breast cancer (MBC) progressing after treatment with an anthracycline and a taxane; approval was based on the results of two phase III trials comparing the combination with capecitabine monotherapy. An array of preclinical studies in multiple solid tumor types show that ixabepilone demonstrates therapeutic synergy with targeted therapies including trastuzumab, bevacizumab, brivanib, and cetuximab; with immune-modulating agents such as anti-CTLA-4 antibody; and with other chemotherapy drugs such as irinotecan and epirubicin. Notably, experiments in several xenograft models show that ixabepilone provides greater antitumor synergism when combined with bevacizumab than either paclitaxel or nab-paclitaxel combined with bevacizumab. These preclinical findings provide a foundation for ongoing phase II clinical trials using ixabepilone in combination with trastuzumab or lapatinib in HER2-positive breast cancer; with bevacizumab in breast cancer, endometrial cancer, renal cancer, and non-small cell lung cancer (NSCLC); with cetuximab in breast cancer, NSCLC, and pancreatic cancer; and with brivanib, dasatinib, sorafinib, sunitinib, or vorinostat in MBC. Preliminary results from several of these trials suggest that ixabepilone-based combinations have promising anticancer activity.<\/jats:p>","DOI":"10.1177\/1758834010386402","type":"journal-article","created":{"date-parts":[[2010,10,20]],"date-time":"2010-10-20T21:11:00Z","timestamp":1287609060000},"page":"11-25","source":"Crossref","is-referenced-by-count":24,"title":["Synergistic activity of ixabepilone plus other anticancer agents: preclinical and clinical evidence"],"prefix":"10.1177","volume":"3","author":[{"given":"Francis","family":"Lee","sequence":"first","affiliation":[{"name":"Bristol-Myers Squibb Company, P.O. Box 4000, K22-03, Princeton, NJ 08543, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria N.","family":"Jure-Kunkel","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Company, Princeton, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Salvati","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Company, Princeton, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2010,10,20]]},"reference":[{"key":"bibr1-1758834010386402","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-006-7304-8"},{"key":"bibr2-1758834010386402","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200767170-00008"},{"key":"bibr3-1758834010386402","doi-asserted-by":"publisher","DOI":"10.1021\/bi0121611"},{"key":"bibr4-1758834010386402","first-page":"2325","volume":"55","author":"Bollag D.M.","year":"1995","journal-title":"Cancer Res"},{"key":"bibr6-1758834010386402","doi-asserted-by":"publisher","DOI":"10.3816\/CBC.2008.n.026"},{"key":"bibr7-1758834010386402","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.24.1455"},{"key":"bibr8-1758834010386402","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-006-9006-7"},{"key":"bibr9-1758834010386402","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.10.0784"},{"key":"bibr10-1758834010386402","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200868060-00002"},{"key":"bibr11-1758834010386402","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.20.6995"},{"key":"bibr12-1758834010386402","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.09.042"},{"key":"bibr13-1758834010386402","author":"Hortobagyi G.N.","year":"2008","journal-title":"ASCO Breast Cancer Symposium"},{"key":"bibr14-1758834010386402","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.02.4448"},{"key":"bibr15-1758834010386402","first-page":"2008","volume":"26","author":"Jure-Kunkel M.N.","year":"2008","journal-title":"Clin Oncol"},{"key":"bibr16-1758834010386402","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-0015"},{"key":"bibr16a-1758834010386402","unstructured":"Lee, F.Y. 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