title: Ixabepilone, a new treatment option for metastatic breast cancer.
abstract: Patients with metastatic breast cancer (MBC) who develop resistance to anthracyclines and taxanes have limited therapeutic options. There is an unmet need for agents that can overcome tumor resistance and are effective in treating drug-resistant disease. The novel epothilone B analog, ixabepilone, binds to β-tubulin and stabilizes microtubules, leading to growth inhibition and apoptosis. Ixabepilone is able to overcome common mechanisms of resistance that limit the efficacy of many chemotherapeutic agents such as anthracyclines, taxanes, and capecitabine. Single-agent ixabepilone has clinical activity and a manageable safety profile against several different solid tumors including MBC, nonsmall cell lung cancer (NSCLC), and prostate cancer. Several phase II and III trials have demonstrated that ixabepilone-as monotherapy and in combination with capecitabine-is active in patients with pretreated or resistant MBC. Ixabepilone is the first epothilone approved for use as monotherapy or in combination with capecitabine in the treatment of metastatic or locally advanced breast cancer that is resistant or refractory to anthracyclines, taxanes, and/or capecitabine. Further clinical studies are evaluating the combination of ixabepilone with targeted agents such as trastuzumab or bevacizumab to further define the role of this novel agent in the treatment of MBC.
authors.affiliation: Department of Medicine, Cancer Institute of New Jersey, New Brunswick, 08901 USA. toppmede@umdnj.edu
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Toppmeyer
authors.forename: Susan
authors.initials: S
authors.lastname: Goodin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069287:Capecitabine; D002986:Clinical Trials as Topic; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004357:Drug Synergism; D034261:Epothilones / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D015337:Multicenter Studies as Topic
chemical_list: D000970:Antineoplastic Agents; D034261:Epothilones; D003841:Deoxycytidine; D000069287:Capecitabine; C430592:ixabepilone; D005472:Fluorouracil