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J Oncol Pharm Pract · Jun 2009
ReviewThe optimal therapeutic use of ixabepilone in patients with locally advanced or metastatic breast cancer.
- Boehnke MichaudLauraLUniversity of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA. lboehnke@mdanderson.org.
- University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA. lboehnke@mdanderson.org
- J Oncol Pharm Pract. 2009 Jun 1; 15 (2): 95-106.
BackgroundThe epothilones are a new class of microtubule-stabilizing drugs that exert potent antitumor activity against taxane-resistant and multidrug resistant cell lines. The most clinically advanced member of this class is the semisynthetic epothilone B derivative ixabepilone.PurposeThis article reviews the preclinical and clinical data on ixabepilone in patients with locally advanced and metastatic breast cancer (MBC) and provides guidance for pharmacists on its optimal use.Data SourcePubMed and conference proceedings through August 2008.ResultsIn preclinical studies, ixabepilone has demonstrated potent antitumor activity and low susceptibility to mechanisms that confer tumor resistance. Clinically meaningful benefits have been achieved with ixabepilone monotherapy in phase 2 trials of patients with MBC who have failed previous chemotherapies (anthracyclines, taxanes, or capecitabine). In a randomized, phase 3 trial, the combination of ixabepilone and capecitabine proved more effective than capecitabine alone after the failure of taxane and anthracycline regimens. At the recommended dose and schedule, the therapeutic ratio of ixabepilone is generally favorable, and its adverse effects (notably neutropenia and peripheral neuropathy) are generally manageable and reversible.ConclusionIxabepilone represents an advance in the treatment of anthracycline - and taxane-pretreated MBC. Future studies will define its efficacy in combination with other drugs used in the treatment of MBC, as well as in other types of cancer.
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