Ixabepilone

• Class: Microtubule-stabilizing agent – epothilone analog (semisynthetic).
• Origin: Semisynthetic derivative of epothilone B from the bacterium Sorangium cellulosum.

Mechanism of Action (MOA)

• Binds to β-tubulin → stabilizes microtubules → prevents depolymerization.
• Leads to mitotic arrest in G2/M phase → apoptosis.
• Active in taxane-resistant tumors, including those with P-glycoprotein overexpression or β-tubulin mutations.

Clinical Uses

• Metastatic or locally advanced breast cancer:
  • Especially taxane- and anthracycline-resistant tumors.
• Investigational/less common: other solid tumors (lung, prostate).

Dosing (Adults)

• 40 mg/m² IV over 3 hours, every 3 weeks.
• Premedication:
  • H1/H2 antihistamines sometimes given due to hypersensitivity risk.
  • Corticosteroids are not routinely required (unlike taxanes with Cremophor).
• Dose adjustments: hepatic impairment (reduce or avoid if bilirubin ≥1.5× ULN).

Toxicities

• Dose-limiting: Peripheral neuropathy (sensory, sometimes motor).
• Myelosuppression (neutropenia, less commonly thrombocytopenia/anemia).
• Fatigue, alopecia, nausea, diarrhea.
• Hypersensitivity reactions are rare compared to paclitaxel.
• Rare: hepatotoxicity, myalgia, arthralgia.

Monitoring

• CBC with differential prior to each cycle.
• Neurologic exam for peripheral neuropathy.
• Liver function tests.
• Infusion-related reactions (rare, supportive care as needed).

Summary

Ixabepilone (Ixempra®) is a microtubule-stabilizing epothilone analog used in taxane-resistant metastatic breast cancer. Main toxicities are neuropathy and myelosuppression, with a lower risk of hypersensitivity compared to taxanes. Dose adjustments are required for hepatic impairment.