Ixabepilone

Diagram of the molecular structure of Ixabepilone
Brand name: Ixempra®
IUPAC: (1R,5S,6S,7R,10S,14S,16S)-6,10-dihydroxy-1,5,7, 9,9-pentamethyl-14-[(E)-1-(2-methyl-1,3-thiazol- 4-yl)prop-1-en-2-yl]-17-oxa-13-azabicyclo[14.1.0] heptadecane-8,12-dione
FDA approval: Yes
Usage:

Ixempra® (ixabepilone) was approved by the FDA in 2007. Ixabepilone is used in combination with capecitabine to treat metastaticThe term for a cancer that has spread beyond its point of origin. Metastatic disease is responsible for the majority of cancer deaths. or locally advanced breast cancer after treatments with an anthracycline and a taxaneA derivative of the yew tree. This compound is the basis for several related chemotherapy drugs that work by inhibiting the function of microtubules. have failed. Ixabepilone is used by itself (as a monotherapy) to treat metastatic or locally advanced breast cancer after treatments with an anthracycline, a taxane, and a capecitabine have failed. Examples of anthracyclines include doxorubicin and epirubicin. Examples of taxanes include paclitaxel and docetaxel.1

Mechanism:

Ixabepilone (Ixempra®) is a microtubuleA cable-like structure that is part of the cytoskeleton composed of long chains of the protein tubulin. Microtubules give a cell shape, aid in cellular motility and are very important in cell division. Microtubules grow and shrink depending on the needs of the cell. The anticancer drugs taxol, vincristine and vinblastine (and their derivatives) all work by interfering with the function of microtubules. function inhibitor and a member of the epothilone class of anticancer agents. Ixabepilone binds to beta-tubulin subunits on microtubules, prohibiting them from depolymerizing during mitosisThe portion of the cell cycle (M stage) during which a cell divides into two (usually identical) daughter cells.. This halts cell division and eventually leads to cell death.1

The above diagram shows the 3D conformer Ixabepilone.

 

Side effects:

Fatigue, myalgia (muscle pain) or arthralgia (joint pain), alopecia (hair loss), nausea, vomiting, stomatitis (inflammationA reaction to tissue damage or invasion. Small blood vessels become leaky, leading to redness and swelling. Cells of the immune system migrate to the area and can release chemicals and proteins that cause damage to the structures/cells nearby. of the mucous linings of the mouth) mucositis (inflammation of the mucous linings of the digestive tract), and diarrhea.1

Contraindications:

The most common toxicities associated with ixabepilone are peripheral neuropathy, myelosuppressionThe decreased activity of the blood cell precursors located in the bone marrow. Both red and white blood cells in the bloodstream originate from these cells which are often short-lived and are replaced constantly by rapidly dividing precursor stem cells. Chemotherapy agents, radiation and many other cancer treatments are designed to attack rapidly dividing cells and inhibit the activity of these normal bone marrow cells. Several side effects of cancer treatment, such as anemia and a decreased ability to fight infections (immunosuppression) are due to the effects of these treatments on bone marrow cells. (particularly of white blood cells) and hypersensitivity reactions. Due to the potential for alteration of ixabepilone metabolismThe sum of all reactions in a cell or animal. Processes that lead to the creation of biomolecules such as proteins and nucleic acids are termed anabolic pathways. Processes in which biomolecules are broken down, such as the digestion of foods, are termed catabolic. Metabolism is a term that encompasses both sets of processes., patients taking strong CYP3A4 inhibitors or inducers should be treated with caution. Ixabepilone has potential to harm a developing fetus, therefore prospective mothers should be warned of this risk and women should avoid becoming pregnant while receiving treatment ixabepilone treatment.1

  • 1.a. b. c. d. Chu, E., & DeVita, V. T. (2015). Physicians' cancer chemotherapyTreatment of cancer patients with anticancer drugs. Commonly called 'chemo'. These drugs work by attacking cell growth or division. Often these agents are used in combination to take advantage of their different modes of attack on cell division. drug manual 2015. Burlington, MA: Jones & Bartlett Learning.