Company:

Bristol-Myers Squibb

Antineoplastic (epothilone microtubule inhibitor)

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

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.

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

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 to capecitabine monotherapy. The primary endpoint 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 to capecitabine alone. The median PFS was 5.7 months for the combination compared to 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 ≥2 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).

Pretreat with both H₁ and H₂ blockers 1 hr before infusion; and with steroid if previous hypersensitivity reaction occurred. 40mg/m² by IV infusion over 3 hrs, once every 3 weeks. Use max body surface area (BSA) of 2.2m² to calculate dose if BSA >2.2m². Moderate hepatic impairment (as monotherapy): initially 20mg/m2 per dose; max 30mg/m² per dose (see literature). Neuropathy, myelosuppression, concomitant CYP3A4 inhibitors: reduce dose (see literature).

Not recommended.

Baseline neutrophils <1500cells/mm³ or platelets <100,000/mm³. AST or ALT >2.5xULN or bilirubin >1xULN (in combination with capecitabine).

Monitor liver function at baseline and periodically. Hepatic impairment (ALT or AST >10xULN or bilirubin >3xULN: not recommended; ALT or AST >5xULN: 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.

Potentiated by strong CYP3A4 inhibitors; avoid (eg, azole antifungals, protease inhibitors, certain macrolides, nefazodone, grapefruit juice). Antagonized by strong CYP3A4 inducers (eg, phenytoin, carbamazepine, rifampin, phenobarbital). Avoid St. John’s wort.

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

Kit—1 vial (w. diluent)

12/13/07