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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-12-16
pubmed:abstractText
Primary drug resistance, defined as disease progression as best response to treatment, presents an important problem in everyday clinical practice. Primary taxane resistance, reported in up to 55% of patients with breast cancer, plays a critical role in minimizing the efficacy of taxane-based chemotherapy for metastatic breast cancer (MBC). The epothilones are a novel class of antineoplastic agents, developed to overcome tumor-resistance mechanisms. Ixabepilone, the first drug in this class, stabilizes microtubule polymerization, and induces cell-cycle arrest and apoptosis. Ixabepilone demonstrates low susceptibility to different and multiple mechanisms of drug resistance that play a crucial role in primary taxane resistance, such as tumor overexpression of neuronal-specific beta-tubulin isotype III and drug-efflux transporters. In phase II trials, ixabepilone demonstrated proven activity in patients with MBC whose tumors had primary or secondary resistance to taxanes and other agents. Ixabepilone also demonstrated activity in patients with tumor types such as renal-cell cancer and pancreatic cancer that are usually intrinsically insensitive to chemotherapy, including taxanes. To determine the activity of ixabepilone in patients with primary taxane resistance, a retrospective analysis of patient subsets from 2 clinical trials was conducted. Ixabepilone demonstrated clinical activity as monotherapy, and in combination with capecitabine, in patients with MBC who had disease progression as best response to previous taxane therapy. Response rates in patients with primary taxane resistance were comparable to responses observed in total patient populations. The clinical results support the hypothesis that ixabepilone can overcome or circumvent primary mechanisms of resistance to taxanes and other chemotherapeutic agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1526-8209
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
487-92
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Activity of ixabepilone in patients with metastatic breast cancer with primary resistance to taxanes.
pubmed:affiliation
Sarah Cannon Research Institute, Nashville, TN 37203, USA. dyardley@tnonc.com
pubmed:publicationType
Journal Article, Review