Manufacturer:

Eisai Pharmaceuticals

Pharmacological Class:

Antineoplastic agent ­(non-taxane microtubule dynamics inhibitor).

Active Ingredient(s):

Eribulin mesylate 0.5mg/mL, solution for IV injection.

Indication(s):

Treatment of metastatic breast cancer in patients who have previously received at least two chemotherapeutic regimens for metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.

Pharmacology:

Eribulin mesylate is a synthetic analogue of a substance found in Halichondria okadai, a marine sponge. It is a non-taxane ­microtubule dynamics inhibitor that inhibits the growth phase of microtubules without ­affecting the shortening phase. It also sequesters tubulin into nonproductive aggregates. Its tubulin-based antimitotic mechanism leads to G₂/M cell-cycle block, disruption of mitotic spindles and, ultimately, apoptotic cell death after prolonged mitotic blockage.

Eribulin is not significantly metabolized and is primarily eliminated unchanged in the feces.

Clinical Trials:

Study 1 compared eribulin and single-agent therapy in an open-label, randomized, multicenter trial involving 762 patients with metastatic breast cancer who had received at least two chemotherapeutic regimens for metastatic disease and had disease progression within 6 months of their last chemotherapy regimen. Randomization was stratified geo­graph­ically, by HER2/neu status and prior capecita­bine exposure. The control group received either 97% chemotherapy (eg, 26% vinorelbine, 18% gemcitabine, 18% capecitabine, 16% taxane, 9% anthracycline, 10% other chemotherapy) or 3% hormonal therapy. The main efficacy outcome was overall survival. A statis­tically ­significant improvement in overall survival was seen in the patients given eribulin (13.1 months) compared with the control group (10.6 months).

Legal Classification:

Rx

Adults:

Give by IV injection over 2–5 minutes. 1.4mg/m² on Days 1 and 8 of a 21-day cycle. Mild hepatic impairment (Child-Pugh A) or moderate renal impairment (CrCl 30–50mL/min): 1.1mg/m² on Days 1 and 8 of a 21-day cycle. Moderate hepatic impairment (Child-Pugh B): 0.7mg/m² on Days 1 and 8 of a 21-day cycle. Hold dose for ANC <1000/mm³, platelets <75000/mm³, or grade 3 or 4 non-hematological toxicities. Delay or reduce dose according to toxicities; see literature. Do not re-escalate dose after it is reduced.

Children:

<18 years: not recommended.

Warnings/Precautions:

Monitor CBCs; increase frequency of monitoring if grade 3 or 4 cyto­penias develop, delay and reduce subsequent doses if febrile neutropenia or grade 4 neutro­penia lasting >7 days develops. Monitor for peripheral neuropathy; withhold dose if grade 3 or 4 peripheral neuropathy develops until ­resolution to grade 2 or less. Congenital long QT syndrome: avoid. CHF, bradyarrhythmias, electrolyte abnormalities: monitor ECG for prolonged QT interval. Correct electrolyte abnormalities (K⁺, Mg⁺) before treatment; mon­itor. Severe hepatic impairment (Child-Pugh C) or severe renal impairment (CrCl<30mL/min): insufficient data. Pregnancy (Cat.D), nursing mothers: not recommended.

Interaction(s):

Caution with other drugs that prolong QT interval (eg, Class IA and III ­antiarrhythmics); monitor.

Adverse Reaction(s):

Neutropenia, anemia, asthenia/fatigue, alopecia, peripheral neuropathy, nausea, constipation, febrile neutropenia; possible QT prolongation, elevated liver enzymes.

Notes:

Do not mix with dextrose-containing solutions. Do not administer in same line as other drugs or fluids.

How Supplied:

Single-use vial (2mL)—1