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Epothilones in the treatment of breast cancer: Review of clinical experience
Author(s) -
XU Binghe
Publication year - 2008
Publication title -
asia‐pacific journal of clinical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 29
eISSN - 1743-7563
pISSN - 1743-7555
DOI - 10.1111/j.1743-7563.2008.00194.x
Subject(s) - epothilones , ixabepilone , epothilone , medicine , taxane , paclitaxel , docetaxel , breast cancer , metastatic breast cancer , oncology , cancer , surgical oncology , pharmacology , biology , chemistry , combinatorial chemistry , genetics
The author will be discussing the off label use of ixabepilane in the management of metastatic breast cancer in this review. Abstract Antimicrotubule agents have emerged as a critical component of our armamentarium of chemotherapeutic drugs for breast cancer treatment. The taxanes paclitaxel and docetaxel are among the most widely used agents because of their proven efficacy in both the metastatic and adjuvant settings. Although the taxanes represented a significant advance for breast cancer treatment, the clinical utility of these drugs may be limited by the rapid emergence of drug resistance as conferred by cellular P‐glycoprotein and alterations in β‐tubulin. The search for the next generation of metastatic tumor antigens has resulted in the discovery of the epothilones, a novel class of microtubule‐stabilizing agents. Although the epothilones possess a mechanism of action that is similar to that of the taxanes, they are structurally unrelated and several members of this novel class of antimicrotubule agents, such as epothilone B and its derivatives, demonstrate greater therapeutic indices and lower susceptibility to multidrug resistance than do the taxanes in preclinical studies. At the time of writing, several epothilones are under clinical investigation for the treatment of cancer patients. Of these, ixabepilone, a semi‐synthetic analog of natural epothilone B, has demonstrated anti‐tumor activity alone or as part of a combination of therapy in patients with taxane‐ and multidrug‐resistant metastatic breast cancer. This article reviews the clinical experience to date with the epothilones with a focus on locally advanced breast cancer and metastatic disease. Clinical experience with second‐generation epothilones under clinical development will be discussed as well.