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Brand name: Ixempra™

• Approved for breast cancer

Full prescribing information ³ is available, including clinical trial information, safety, dosing, drug-drug interactions, and contraindications.

On October 16, 2007, the U.S. Food and Drug Administration (FDA) approved ixabepilone for injection (Ixempra™, made by Bristol-Myers Squibb) for the following two indications:

• Ixabepilone is indicated in combination with capecitabine for the treatment of patients with metastatic or locally advanced breast cancer resistant to treatment with an anthracycline and a taxane, or whose cancer is taxane resistant and for whom further anthracycline therapy is contraindicated.
• Ixabepilone is indicated as monotherapy for the treatment of metastatic or locally advanced breast cancer in patients whose tumors are resistant or refractory to anthracyclines, taxanes, and capecitabine.

A randomized, multinational, open-label trial of 752 patients with locally advanced or metastatic breast cancer evaluated the efficacy and safety of ixabepilone (40 mg/m2 IV once every three weeks) plus capecitabine compared to therapy with capecitabine alone. Patients had previously received an anthracycline and a taxane, had evidence of disease progression or resistance, or, in the case of the anthracycline, received a minimum required cumulative dose.

Treatment arms were balanced with regards to prior therapies, disease sites, hormone receptor status and HER2 expression. Patients receiving combination therapy had a statistically significant improvement in progression-free survival (PFS), defined as radiologic progression or death from any cause (hazard ratio 0.69, p<0.0001). The median PFS was 5.7 months in the combination arm and 4.1 months in the capecitabine alone arm. Patients in the combination arm also had an increased objective tumor response rate. Survival data for this trial are not yet mature.

Ixabepilone monotherapy was evaluated in a single arm trial of 126 patients with metastatic or locally advanced breast cancer who had previously received an anthracycline, a taxane and capecitabine, and who had disease progression or, in the case of the anthracycline, received a minimum required cumulative dose. Ixabepilone was administered at the same dose and schedule as in the combination trial. The objective response rate based on independent radiologic review was 12.4 percent (95 percent CI: 6.9, 19.9). The objective response rate based on investigator assessments was 18.3 percent (95 percent CI: 11.9, 26.1). The median response duration was 6.0 months (95 percent CI: 5.0, 7.6).

Treatment with ixabepilone caused new or worsening peripheral neuropathy in approximately 65 percent of patients treated. Grade 3 or 4 peripheral neuropathy occurred in 23 percent of patients treated with ixabepilone and capecitabine, with no grade 3 or 4 peripheral neuropathy reported in the capecitabine arm. In the ixabepilone monotherapy trial, 14 percent experienced grade 3 or 4 peripheral neuropathy. Neuropathy was generally reversible to grade 1 or better with cessation of therapy.

Ixabepilone in combination with capecitabine resulted in a 68 percent incidence of grade 3 or 4 neutropenia compared to 11 percent with capecitabine alone. Twelve patients receiving ixabepilone in combination with capecitabine died from complications arising from neutropenia.

The incidence of neutropenia related deaths was higher in patients with baseline moderate or severe hepatic impairment when treated with both ixabepilone and capecitabine. This combination should not be used in patients with moderate or severe hepatic impairment. When used as monotherapy, 54 percent of patients treated with ixabepilone experienced grade 3 or 4 neutropenia.

Other commonly observed toxicities (>20 percent) included anemia, leukopenia, thrombocytopenia, fatigue/asthenia, myalgia/arthralgia, alopecia, nausea, vomiting, stomatitis/mucositis, diarrhea, and musculoskeletal pain. The following additional reactions occurred in ≥20 percent in the combination treatment arm: palmar-plantar erythrodysesthesia (hand-foot) syndrome, anorexia, abdominal pain, nail disorder, and constipation.

Glossary Terms

The lack or loss of hair from areas of the body where hair is usually found. Alopecia can be a side effect of some cancer treatments.

A condition in which the number of red blood cells is below normal.

A type of antibiotic that comes from certain types of Streptomyces bacteria. Anthracyclines are used to treat many types of cancer. Anthracyclines damage the DNA in cancer cells, causing them to die. Daunorubicin, doxorubicin, and epirubicin are anthracyclines.

Weakness; lack of energy and strength.

A drug used to treat stage III colon cancer in patients who had surgery to remove the cancer. It is also used to treat metastatic breast cancer that has not improved after treatment with certain other anticancer drugs. Capecitabine is being studied in the treatment of other types of cancer. It is taken up by cancer cells and breaks down into 5-fluorouracil, a substance that kills tumor cells. Capecitabine is a type of antimetabolite. Also called Xeloda.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.

In medicine, the total amount of a drug or radiation given to a patient over time; for example, the total dose of radiation given in a series of radiation treatments.

Effectiveness. In medicine, the ability of an intervention (for example, a drug or surgery) to produce the desired beneficial effect.

Refers to the liver.

A protein involved in normal cell growth. It is found on some types of cancer cells, including breast and ovarian. Cancer cells removed from the body may be tested for the presence of HER2/neu to help decide the best type of treatment. HER2/neu is a type of receptor tyrosine kinase. Also called c-erbB-2, human EGF receptor 2, and human epidermal growth factor receptor 2.

A cell protein that binds a specific hormone. The hormone receptor may be on the surface of the cell or inside the cell. Many changes take place in a cell after a hormone binds to its receptor.

A drug used to treat metastatic or locally advanced breast cancer that has not improved after treatment with certain other anticancer drugs. It is also being studied in the treatment of other types of cancer. Ixabepilone stops the growth of tumor cells by blocking cell division. It is a type of epothilone analog. Also called BMS-247550 and Ixempra.

A condition in which there is a lower-than-normal number of leukocytes (white blood cells) in the blood.

Cancer that has spread from where it started to nearby tissue or lymph nodes.

A statistics term. The middle value in a set of measurements.

Having to do with metastasis, which is the spread of cancer from the primary site (place where it started) to other places in the body.

A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth.

Having to do with muscles, bones, tendons, ligaments, joints, and cartilage.

Pain in a muscle or group of muscles.

A condition in which there is a lower-than-normal number of neutrophils (a type of white blood cell).

A measurable response.

A nerve problem that causes pain, numbness, tingling, swelling, or muscle weakness in different parts of the body. It usually begins in the hands or feet and gets worse over time. Peripheral neuropathy may be caused by physical injury, infection, toxic substances, disease (such as cancer, diabetes, kidney failure, or malnutrition), or drugs, including anticancer drugs. Also called neuropathy.

The length of time during and after treatment in which a patient is living with a disease that does not get worse. Progression-free survival may be used in a clinical study or trial to help find out how well a new treatment works. Also called PFS.

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.

In medicine, describes a disease or condition that does not respond to treatment.

The percentage of patients whose cancer shrinks or disappears after treatment.

Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. Also called significant.

Inflammation or irritation of the mucous membranes in the mouth.

A type of drug that blocks cell growth by stopping mitosis (cell division). Taxanes interfere with microtubules (cellular structures that help move chromosomes during mitosis). They are used to treat cancer. A taxane is a type of mitotic inhibitor and antimicrotubule agent.

A condition in which there is a lower-than-normal number of platelets in the blood. It may result in easy bruising and excessive bleeding from wounds or bleeding in mucous membranes and other tissues.