The optimal therapeutic use of ixabepilone in patients with locally advanced or metastatic breast cancer.
BACKGROUND
The 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.


OBJECTIVE
This 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.


METHODS
PubMed and conference proceedings through August 2008.


RESULTS
In 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.


CONCLUSIONS
Ixabepilone 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.
Boehnke Michaud
Laura
L
University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA. lboehnke@mdanderson.org
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D000069287:Capecitabine; D002986:Clinical Trials as Topic; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D034261:Epothilones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009503:Neutropenia / Q000139:chemically induced; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D011292:Premedication; D050257:Tubulin Modulators / Q000008:administration & dosage
D000970:Antineoplastic Agents; D034261:Epothilones; D050257:Tubulin Modulators; D003841:Deoxycytidine; D000069287:Capecitabine; C430592:ixabepilone; D005472:Fluorouracil