Ixempra- When breast cancer resists other drugs

Company:

Bristol-Myers Squibb

Pharmacologic class:

Antineoplastic (epothilone microtubule inhibitor)

Active ingredient:

Ixabepilone 15 mg/vial, 45 mg/vial; powder; for IV infusion after constitution and dilution; diluent contains alcohol, polyoxyethylated castor oil.

Indication:

Metastatic or locally advanced breast cancer: In combination with capecitabine after failure of an anthracycline and a taxane; and as monotherapy after failure of an anthracycline, a taxane, and capecitabine.

Pharmacology:

Ixabepilone is a semisynthetic analog of epothilone B, a microtubule inhibitor. It binds to microtubules, thus disrupting cell division. It blocks cells from dividing in the mitotic phase of the cell-division cycle, causing cell death.

Clinical trials:

A trial involving 752 patients with metastatic or locally advanced breast cancer was conducted to assess the efficacy and safety of ixabepilone in combination with capecitabine compared with capecitabine monotherapy. The primary end point was progression-free survival (PFS) (time from randomization to radiologic progression, clinical progression of measurable skin lesions, or death).

Ixabepilone in combination with capecitabine resulted in statistically significant improvement in PFS compared with capecitabine alone. The median PFS was 5.7 months for the combination compared with 4.1 months for capecitabine monotherapy.

A study in 126 women with metastatic or locally advanced breast cancer whose tumors had recurred or had progressed following two or more chemotherapy regimens was conducted to evaluate the use of ixabepilone as monotherapy. The objective tumor response rates were 12.4% (independent radiologic review assessment) and 18.3% (investigator assessment).

Adults:

Pretreat with both H1 and H2 blockers one hour before infusion; and with steroid if previous hypersensitivity reaction occurred.

40 mg/m2 by IV infusion over three hours, once every three weeks. Use maximum body surface area (BSA) of 2.2 m2 to calculate dose if BSA >2.2m2. Moderate hepatic impairment (as monotherapy): initially 20 mg/m2 per dose; max 30 mg/m2 per dose. Neuropathy, myelosuppression, concomitant CYP3A4 inhibitors: reduce dose.

Children:

Not recommended.

Contraindications:

Baseline neutrophils <1,500 cells/µL or platelets <100,000/µL. AST or ALT >2.5×ULN or bilirubin >1×ULN (in combination with capecitabine). Precautions: Monitor liver function at baseline and periodically. Hepatic impairment (ALT or AST >10×ULN or bilirubin >3×ULN: not recommended; ALT or AST >5×ULN: limited data, use caution). Diabetes. Neuropathy. Cardiac disease (discontinue if cardiac ischemia or cardiac dysfunction occurs). Monitor for neuropathy, neutropenia. Pregnancy (Cat. D), nursing mothers: not recommended.

Interactions:

Potentiated by strong CYP3A4 inhibitors; avoid (e.g., azole antifungals, protease inhibitors, certain macrolides, nefazodone, grapefruit juice).

Antagonized by strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, phenobarbital). Avoid St. John’s wort.

Adverse reactions:

Peripheral sensory neuropathy, fatigue, asthenia, myalgia, arthralgia, alopecia, GI upset, stomatitis, mucositis, musculoskeletal pain, palmar- plantar erythrodysesthesia syndrome, anorexia, abdominal pain, nail disorder; myelosuppression (neutropenia, leukopenia, anemia, thrombocytopenia); hypersensitivity reactions; others.

How supplied:

Kit—1 vial (with diluent)

For more information, call 888.493.6772 or visit www.IXEMPRA.com

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