Ixabepilone is a cell cycle inhibitor that targets tubulin (in contrast to the cell cycle inhibitor flavopiridol, which targets cyclin dependent kinases). It is an intravenous drug usually administered every 3 weeks.
NCI Drug dictionary definition: ixabepilone - “an orally bioavailable semisynthetic analogue of epothilone B with antineoplastic activity. Ixabepilone binds to tubulin and promotes tubulin polymerization and microtubule stabilization, thereby arresting cells in the G2-M phase of the cell cycle and inducing tumor cell apoptosis. This agent demonstrates antineoplastic activity against taxane-resistant cell lines.”
Ixabepilone was approved by the FDA in fall 2007 for treatment of breast cancer, as summarized in this news story. As of September 2008, ixabepilone is not yet available in the European Union.
Ixabepilone (brand name Ixempra) is manufactured by Bristol Myers Squibb. Information from the manufacturer is available at the website http://www.ixempra.com/
Clinical Trials with ixabepilone
Currently Ixabepilone is in a combination trial with dasatinib (a tyrosine kinase inhibitor drug with known activity against GIST). This Phase I study aims to ascertain the highest dose of ixabepilone and dasatinib in combination that can be given without causing severe side effects. See the trial link at clinicaltrials.gov The trial is no longer recruiting but is ongoing. Both ixabepilone (which is given intravenously) and dasatinib (given as a pill) have individually been tested in several thousand patients, however the combination of the two drugs has not yet been tested in humans. Thus it is hoped that the combination of TKI inhibition (via dasatinib) and cell cycle arrest (the Ixabepilone interrupting cell division) will provide two different angles of attack simultaneously and prove effective against imatinib resistant metastatic GIST.
References for Additional Information
1: Lee FY, Borzilleri R, Fairchild CR, Kamath A, Smykla R, Kramer R, Vite G.
Preclinical discovery of ixabepilone, a highly active antineoplastic agent.
Cancer Chemother Pharmacol. 2008 Dec;63(1):157-66. Review.
2: Rivera E, Lee J, Davies A.
Clinical development of ixabepilone and other epothilones in patients with advanced solid tumors.
Oncologist. 2008 Dec;13(12):1207-23.
PMID: 19088324 FREE ACCESS
3: Goodin S.
Ixabepilone: a novel microtubule-stabilizing agent for the treatment of metastatic breast cancer.
Am J Health Syst Pharm. 2008 Nov 1;65(21):2017-26.
4: Goodin S.
Novel cytotoxic agents: epothilones.
Am J Health Syst Pharm. 2008 May 15;65(10 Suppl 3):S10-5. Review.
5: Denduluri N, Swain SM.
Ixabepilone for the treatment of solid tumors: a review of clinical data.
Expert Opin Investig Drugs. 2008 Mar;17(3):423-35. Review.
6: Thomas E, Tabernero J, Fornier M, Conté P, Fumoleau P, Lluch A, Vahdat LT, Bunnell CA, Burris HA, Viens P, Baselga J, Rivera E, Guarneri V, Poulart V, Klimovsky J, Lebwohl D, Martin M.
Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, in patients with taxane-resistant metastatic breast cancer.
J Clin Oncol. 2007 Aug 10;25(23):3399-406.