TITLE

Activity of Ixabepilone in Patients with Metastatic Breast Cancer with Primary Resistance to Taxanes

AUTHOR(S)
Yardley, Denise A.
PUB. DATE
December 2008
SOURCE
Clinical Cancer Update;Dec2008, Vol. 2 Issue 1, p5
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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 β-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.
ACCESSION #
43593351

 

Related Articles

  • Resistance to chemotherapy via Stat3-dependent overexpression of Bcl-2 in metastatic breast cancel cells. Real, Pedro J.; Sierra, Angels; de Juan, Ana; Segovia, Jose C.; Lopez-Vega, Jose M.; Fernandez-Luna, Jose L. // Oncogene;10/31/2002, Vol. 21 Issue 50, p7611 

    Examines the pathways that activate the resistance to chemotherapy in metastatic breast cancer cells. Materials and methods; Results of the study; Discussion of findings.

  • Breast cancer, advanced.  // Annals of Oncology;Oct2010 Supplement 8, Vol. 21 Issue suppl_8, pviii96 

    No abstract available.

  • Treatment of metastatic breast cancer: second line and beyond. Roché, H.; Vahdat, L. T. // Annals of Oncology;May2011, Vol. 22 Issue 5, p1000 

    Increasing use of standard chemotherapy, especially anthracycline- and taxane-based therapies, in early-stage breast cancer has led to a corresponding increase in heavily pretreated and/or treatment-resistant cases of metastatic breast cancer (MBC). Thus, second and later lines of MBC therapy...

  • High-Dose Chemotherapy in Breast Cancer. Lake, Diana E.; Hudis, Clifford A. // Drugs;2004, Vol. 64 Issue 17, p1851 

    High-dose chemotherapy is based on the scientific hypothesis that escalating the dose of drug will overcome drug resistance and improve outcome. Autologous bone marrow transplantation and, more recently, peripheral stem cell transplantation used as a means to restore marrow, made this a viable...

  • The effect of HER-2/neu overexpression on chemotherapeutic drug sensitivity in human breast and ovarian cancer cells. Pegram, Mark D; Finn, Richard S; Arzoo, Karo; Beryt, Malgorzata; Pietras, Richard J; Slamon, Dennis J // Oncogene;7/31/97, Vol. 15 Issue 5, p537 

    Recent studies indicate that oncogenes may be involved in determining the sensitivity of human cancers to chemotherapeutic agents. To define the effect of HER-2/neu oncogene overexpression on sensitivity to chemotherapeutic drugs, a full-length, human HER-2/neu cDNA was introduced into human...

  • LIMK1/TPPP1/HDAC6 Is a Dual Actin and Microtubule Regulatory Complex That Promotes Drug Resistance. Schofield, Alice V.; Gamell, Cristina; Bernard, Ora // Advances in Bioscience & Biotechnology;Mar2014, Vol. 5 Issue 4, p353 

    In this study, we identified a novel protein complex consisting of LIM-Kinase 1 (LIMK1), Histone deacetylase 6 (HDAC6) and Tubulin Polymerization Promoting Protein 1 (TPPP1). Under basal conditions, assembly of the LIMK1/TPPP1/HDAC6 complex results in both inhibition of HDAC6 activity and LIMK1...

  • Pharmacological Strategies to Overcome HER2 Cross-Talk and Trastuzumab Resistance. Nahta, R. // Current Medicinal Chemistry;Mar2012, Vol. 19 Issue 7, p1065 

    Approximately 20-30% of breast cancers show increased expression of the HER2 receptor tyrosine kinase. Trastuzumab (Herceptin) is a clinically approved anti-HER2 monoclonal antibody. Many patients with HER2-overexpressing metastatic breast cancer respond to trastuzumab; however, a subset display...

  • Lapatinib. Toi, Masakazu // Drugs;2007, Vol. 67 Issue 14, p2109 

    The article focuses on the efficacy of the dual kinase inhibitor lapatinib in improving prognosis and quality of life of patients with breast cancer. The drug treatment curbs the epidermal growth factor receptor and human epidermal receptor (HER)2. Several clinical trials have established it to...

  • Trastuzumab in the Adjuvant Treatment of HER2-Positive Early Breast Cancer Patients: A Meta-Analysis of Published Randomized Controlled Trials. Wenjin Yin; Yiwei Jiang; Zhenzhou Shen; Zhimin Shao; Jinsong Lu // PLoS ONE;2011, Vol. 6 Issue 6, p1 

    Background: Adjuvant trastuzumab therapy has yielded conflicting results for overall survival, concerns about central nervous system (CNS) metastasis, and questions about optimal schedule. Therefore, we carried out a meta-analysis to assess the benefits of concurrent or sequential trastuzumab...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics