Eribulin mesylate, a synthetic analog of halichondrin B and nontaxane microtubule dynamics inhibitor, is an antineoplastic agent.1, 2, 4, 5, 6, 7, 10, 12, 13, 17, 23
Eribulin mesylate is used for the treatment of metastatic breast cancer in patients who have previously received at least 2 chemotherapeutic regimens for the treatment of metastatic disease; prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.1, 2, 12, 23
The current indication for eribulin is based principally on the results of an open-label, randomized, multicenter phase 3 trial (the EMBRACE trial) conducted in 762 extensively pretreated women with metastatic or locally recurrent breast cancer.1, 2, 3 This study compared eribulin monotherapy to any single-agent treatment of the physician's choice, which served as a control designed to represent actual clinical options available for the management of metastatic breast cancer.1, 2, 6 Patients who had received from 2 to 5 previous chemotherapy regimens, including an anthracycline- and a taxane-based regimen for adjuvant or metastatic disease (unless contraindicated), and whose disease had progressed within 6 months of their last treatment were enrolled in the study.1, 2 Median age of the patients was 55 years (range: 27-85 years), 92% were Caucasian, and 91% had an ECOG performance status of 0-1.1 Tumor prognostic characteristics, including hormone receptor status, expression of HER2, and site and extent of disease, were similar between the 2 treatment groups.1, 2 Patients were randomized in a 2:1 ratio to receive eribulin (1.4 mg/m2 IV on days 1 and 8 of a 21-day treatment cycle) or any single-agent chemotherapy, hormonal therapy, biologic therapy, radiotherapy, or symptomatic treatment alone.1, 2 The majority of patients in the control group received a chemotherapeutic agent (vinorelbine [26%], gemcitabine [18%], capecitabine [18%], a taxane [16%], an anthracycline [9%], or other chemotherapy [10%]) and the remainder received hormonal therapy (3%).1, 2 Therapy was continued until disease progression, intolerable toxicity, or patient withdrawal for other reasons occurred.2
Overall survival, which was the primary efficacy end point of the EMBRACE trial, was prolonged in patients receiving eribulin compared with those receiving a control therapy (median overall survival of 13.1 and 10.6 months, respectively).1, 2, 3 Patients treated with eribulin had an objective response rate of 11% and a median duration of response of 4.2 months.1, 2 Progression-free survival, a secondary outcome of the study, also was prolonged in the eribulin group compared with the control group, but the difference was less than that observed for overall survival and did not reach statistical significance by independent (versus investigator) review.2, 10 Eribulin was relatively well tolerated; grade 3 or 4 adverse effects that occurred more often with eribulin than with comparator regimens included neutropenia, leukopenia, and peripheral neuropathy.2
Although several drugs (e.g., capecitabine, eribulin, gemcitabine, ixabepilone, vinorelbine) have been used in the treatment of anthracycline- and taxane-refractory metastatic breast cancer, there currently is no generally accepted standard of care for the management of patients with such advanced and heavily pretreated disease.1, 2, 5, 6, 13, 14, 15, 16, 17, 19, 23, 35 Some clinicians recommend that choice of therapy should therefore be individualized based on factors such as the patient's disease stage and tumor type, performance status, quality of life, preferences, treatment history including toxicity, underlying medical conditions, and the expected benefits and risks of each treatment option.14, 15, 16, 35
Patients receiving eribulin mesylate should be assessed for peripheral neuropathy and a complete blood cell count (CBC) should be performed prior to administration of each dose of the drug.1 The dose of eribulin should be modified or temporarily withheld for hematologic and non-hematologic toxicities according to the degree of the toxicities.1 (See Dosage and Administration: Dosage Modification for Toxicity.)
Because eribulin may cause nausea and vomiting,1, 2 use of prophylactic antiemetics, including corticosteroids, may be considered.33
Routine premedication to prevent hypersensitivity reactions is not necessary with eribulin.2, 4, 7, 10, 16, 26
Eribulin mesylate is administered IV, either as an injection or short infusion, over 2-5 minutes.1, 25, 27 The drug should be given only by IV administration.1 In clinical trials, the drug was given IV over 1-60 minutes† either directly or diluted in 0.9% sodium chloride injection to a concentration of 0.01-0.1 mg/mL; the infusion time was independent of whether the injection was diluted or undiluted.25
Good peripheral venous access or a patent central line should be ensured prior to administration.25 The injection does not appear to be a vesicant or irritant; if extravasation occurs, there is no specific antidote and treatment should be symptomatic.25
Eribulin mesylate injection is commercially available as a ready-to-use solution containing 0.5 mg of eribulin mesylate per mL in single-use vials.1, 10, 26 The appropriate dose of the drug should be withdrawn from the vial and administered either undiluted or diluted with 100 mL of 0.9% sodium chloride injection.1 The manufacturer states that eribulin injection should not be diluted or administered with dextrose solutions; the injection also should not be administered in the same IV line with other drugs.1
Undiluted solutions of eribulin may be stored in the syringe for up to 4 hours at room temperature or up to 24 hours under refrigeration (4°C).1 Diluted solutions also may be stored for up to 4 hours at room temperature or up to 24 hours under refrigeration.1 Any unused portions of the vial should be discarded.1
Procedures for proper handling and disposal of antineoplastic drugs should be followed when preparing or administering eribulin.24, 25 For additional information on proper procedures for handling antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
Unopened vials of eribulin mesylate injection should be stored in their original cartons at 25°C, but may be exposed to temperatures ranging from 15-30°C.1 Freezing of the vials should be avoided.1
Eribulin is commercially available as eribulin mesylate; dosage of eribulin mesylate is expressed in terms of the mesylate salt.1
Dosage of eribulin mesylate is based on the patient's body surface area.1
For the treatment of metastatic breast cancer in patients who have received at least 2 prior chemotherapeutic regimens (including an anthracycline and a taxane), the recommended dosage of eribulin mesylate in adults is 1.4 mg/m2 administered IV over 2-5 minutes on days 1 and 8 of a 21-day treatment cycle.1, 12, 18, 19, 23 Patients should have an absolute neutrophil count (ANC) of at least 1000/mm3 and a platelet count of at least 75,000/mm3 prior to each dose.1 In addition, any nonhematologic toxicities should have resolved to grade 2 in severity or less before a dose is administered.1 Dose delays and reductions are required in patients who experience severe hematologic and/or nonhematologic toxicities during therapy.1 (See Dosage and Administration: Dosage Modification for Toxicity.)
In the principal efficacy study, eribulin was continued until disease progression, intolerable toxicity, or patient withdrawal for other reasons occurred; patients received a median of 5 cycles (range: 1-23 cycles) of therapy with the drug.1, 2
Dosage Modification for Toxicity
The dose of eribulin mesylate on day 1 or day 8 of the treatment cycle should be withheld if ANC counts are less than 1000/mm3, platelet counts are less than 75,000/mm3, or grade 3 or 4 nonhematologic toxicities are present.1 The dose on day 8 may be delayed for a maximum of 1 week for these toxicities.1 If toxicities resolve or improve to grade 2 in severity or less by day 15, eribulin therapy may be resumed at a reduced dosage (see Table 1) and the next treatment cycle should be initiated no sooner than 2 weeks later.1 If toxicities do not resolve or improve to grade 2 or less within this 1-week time period, the dose should be omitted.1
Permanently Reduce Dosage in Patients Initially Dosed with 1.4 mg/m2 for Any of the Following Toxicities: | Recommended Dosage on Days 1 and 8 of 21-Day Cycle |
|---|---|
ANC <500/mm3 for >7 days | 1.1 mg/m2 |
ANC <1000/mm3 with fever or infection | 1.1 mg/m2 |
Platelets <25,000/mm3 | 1.1 mg/m2 |
Platelets <50,000/mm3 requiring transfusion | 1.1 mg/m2 |
Nonhematologic grade 3 or 4 toxicities | 1.1 mg/m2 |
Omission or delay of day 8 dose in previous cycle for toxicity | 1.1 mg/m2 |
If any of the above events occurs while receiving 1.1 mg/m2, reduce dosage to 0.7 mg/m2. | |
If any of the above events occurs while receiving 0.7 mg/m2, discontinue therapy. | |
The manufacturer recommends that the dosage of eribulin mesylate be reduced to 1.1 mg/m2 on days 1 and 8 of a 21-day cycle in patients with mild (Child-Pugh class A) hepatic impairment and to 0.7 mg/m2 on days 1 and 8 of a 21-day cycle in those with moderate (Child-Pugh class B) hepatic impairment.1, 23 Eribulin has not been studied in patients with severe (Child-Pugh class C) hepatic impairment and the manufacturer does not make specific dosage recommendations for such patients.1 (See Hepatic Impairment under Warnings/Precautions: Specific Populations, in Cautions.)
No dosage adjustment is necessary in patients with mild renal impairment (creatinine clearance of 50-80 mL/minute).1 The manufacturer recommends that the initial dosage of eribulin mesylate be reduced to 1.1 mg/m2 on days 1 and 8 of a 21-day cycle in patients with moderate renal impairment (creatinine clearance of 30-50 mL/minute).1, 23 Eribulin has not been studied in patients with severe renal impairment (creatinine clearance less than 30 mL/minute) and the manufacturer does not make specific dosage recommendations for such patients.1 (See Renal Impairment under Warnings/Precautions: Specific Populations, in Cautions.)
The manufacturer states that there are no known contraindications to the use of eribulin mesylate.1
Neutropenia is the most common adverse effect associated with eribulin mesylate therapy, occurring in 82% of patients in the EMBRACE trial; grade 3 or 4 neutropenia was reported in 28 or 29% of patients receiving the drug, respectively.1, 2, 18, 19 Febrile neutropenia occurred in 5% of patients, and 2 patients (0.4%) died from complications of febrile neutropenia.1, 2 Severe neutropenia (absolute neutrophil count [ANC] less than 500/mm3) lasting more than 1 week was reported in 12% of the patients in this study.1 Patients with serum AST or ALT concentrations exceeding 3 times the upper limit of normal or serum bilirubin concentrations exceeding 1.5 times the upper limit of normal had higher incidences of grade 4 neutropenia and febrile neutropenia than those with normal aminotransferase concentrations.1 In patients with grade 3 or 4 neutropenia, the mean time to nadir neutrophil count within a treatment cycle was approximately 13 days, and the mean time to recovery from severe neutropenia was approximately 8 days.1, 2, 36
A complete blood cell count (CBC) should be obtained prior to administering each dose of eribulin and more frequently in patients who develop grade 3 or 4 cytopenias.1 Administration should be delayed and subsequent doses reduced in patients with febrile neutropenia or grade 4 neutropenia lasting longer than 7 days.1 (See Dosage and Administration: Dosage Modification for Toxicity.) In the EMBRACE trial, granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor was used in 19% of the eribulin-treated patients who developed cytopenias.1, 2
Peripheral neuropathy is a common dose-limiting adverse effect of microtubule inhibitors, including eribulin.1, 2, 4, 7, 18, 19, 21, 26 Peripheral neuropathy of any grade (motor neuropathy, polyneuropathy, sensory neuropathy, paresthesias) was reported in 35% of patients receiving eribulin in the EMBRACE study and was the most common adverse effect resulting in discontinuance of the drug.1, 2 Grade 3 and 4 peripheral neuropathy occurred in 8 and 0.4%, respectively, of patients receiving eribulin in the study; in those who continued therapy, peripheral neuropathy improved to grade 2 or less after the dose was delayed and reduced.1, 2 About 5% of patients experienced neuropathy that lasted for more than 1 year, and 22% developed new-onset or worsening neuropathy that persisted for at least a median follow-up period of 269 days.1
Patients receiving eribulin should be closely monitored for manifestations of peripheral motor and sensory neuropathy (e.g., numbness, tingling, or burning sensation in the hands and/or feet) prior to each dose of eribulin.1 The drug should be withheld in patients who experience grade 3 or 4 peripheral neuropathy until it resolves to grade 2 or less; therapy may then be resumed at a reduced dosage.1 (See Dosage and Administration: Dosage Modification for Toxicity.)
Fetal/Neonatal Morbidity and Mortality
There are no adequate and well-controlled studies of eribulin in pregnant women.1 Because eribulin is a microtubule inhibitor, it is expected to cause fetal harm when administered to pregnant women.1 Embryofetal toxicity and teratogenicity (e.g., increased abortion, increased resorption and death, decreased fetal weight, severe external or soft tissue malformations) have been demonstrated in animals.1 If eribulin is used during pregnancy or the patient becomes pregnant while receiving the drug, the patient should be apprised of the potential fetal hazard.1 (See Advice to Patients.)
Eribulin has been associated with QT-interval prolongation, which appears to be a delayed effect of the drug.1, 3 In an uncontrolled, open-label study, prolongation of the QT interval (maximum QTc change from baseline of 11.4 msec) was observed on day 8 of the treatment cycle, independent of eribulin concentration, in patients receiving the drug; QT-interval prolongation was not observed on day 1.1, 3
Eribulin should be avoided in patients with congenital long QT syndrome.1 Hypokalemia or hypomagnesemia should be corrected prior to initiating eribulin therapy and serum potassium and magnesium concentrations should be monitored periodically during therapy with the drug.1 The manufacturer recommends that ECG monitoring for QT-interval prolongation in patients with congestive heart failure, bradyarrhythmias, and electrolyte abnormalities and in those receiving drugs known to prolong the QT interval (e.g., class Ia and III antiarrhythmic agents).1 (See Drug Interactions: Drugs that Prolong the QT Interval.)
Category D.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions: Warnings/Precautions.)
Not known whether eribulin mesylate is distributed into human milk.1 Because of the potential for serious adverse reactions to eribulin in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.1
Safety and effectiveness of eribulin in pediatric patients younger than 18 years of age have not been established.1
The EMBRACE study did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently to eribulin than younger patients.1 Among 827 patients who received eribulin in clinical studies, 121 (15%) were 65 years of age or older and 17 (2%) were 75 years of age or older.1 No overall differences in safety were observed in these patients compared with those younger than 65 years of age.1
In an open-label study, systemic exposure to eribulin was increased by approximately 1.8- or 2.5-fold in those with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment, respectively.1, 8 Dosage of eribulin should therefore be reduced in patients with mild or moderate hepatic impairment.1 The drug has not been studied in patients with severe (Child-Pugh class C) hepatic impairment.1 (See Dosage and Administration: Special Populations.)
Formal pharmacokinetic studies have not been conducted in patients with renal impairment.1 Available data suggest that dosage adjustment is not required in patients with mild renal impairment (creatinine clearance of 50-80 mL/minute).1 However, a twofold increase in eribulin exposure has been observed in patients with moderate renal impairment (creatinine clearance of 30-50 mL/minute); therefore, a lower initial dosage is recommended in such patients.1 (See Dosage and Administration: Special Populations.)The safety of eribulin in patients with severe renal impairment (creatinine clearance less than 30 mL/minute) has not been studied.1
Adverse effects reported in 25% or more of patients receiving eribulin mesylate in clinical studies included neutropenia,1, 2, 18, 19 anemia,1, 2, 18, 19 asthenia or fatigue,1, 2, 18, 19, 26, 36 alopecia,1, 2, 18, 19, 36 peripheral neuropathy,1, 2, 18, 19 nausea,1, 2, 18, 19, 26, 36 and constipation.1, 2
Among patients with grade 0 or 1 ALT levels at baseline, 18% of eribulin-treated patients experienced grade 2 or greater ALT elevation.1
Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes
Eribulin mesylate is minimally metabolized by cytochrome P-450 (CYP) 3A4 isoenzyme; clinically important pharmacokinetic interactions are not expected with concomitant use of drugs that inhibit CYP3A4.1, 11
In vitro studies indicate that eribulin does not substantially inhibit CYP1 isoenzymes A2, 2C9, 2C19, 2D6, 2E1, or 3A4 and does not induce CYP1 isoenzymes A2, 2C9, 2C19, or 3A4; therefore, eribulin is not expected to alter plasma concentrations of drugs metabolized by these CYP isoenzymes.1, 11 Although eribulin demonstrated some CYP3A4-inhibitory activity in human liver microsomes in one study, the drug did not appear to inhibit the metabolism of several substrates of CYP3A4 (carbamazepine, diazepam, paclitaxel, midazolam, tamoxifen, terfenadine [no longer commercially available in the US]) at clinically relevant concentrations.1, 11
Drugs Affecting the P-glycoprotein Transport System
Eribulin is both a substrate and weak inhibitor of the efflux transporter P-glycoprotein in vitro.1, 10, 11, 13 Clinically important pharmacokinetic interactions are not expected with concurrent use of drugs that inhibit P-glycoprotein (e.g., ketoconazole).1 (See Drug Interactions: Ketoconazole.)
Drugs that Prolong the QT Interval
Potential pharmacologic interaction (additive effect on QT-interval prolongation).1 ECG monitoring is recommended in patients concurrently receiving other drugs known to prolong the QT interval, including class Ia (e.g., quinidine, procainamide) and class III (e.g., amiodarone, sotalol) antiarrhythmic agents, some antipsychotic agents (e.g., chlorpromazine, thioridazine, haloperidol, asenapine, olanzapine, paliperidone, pimozide, quetiapine, ziprasidone), some antibiotics (e.g., gatifloxacin, moxifloxacin), and tetrabenazine.1, 29, 30, 31, 32 (See Prolongation of QT Interval under Cautions: Warnings/Precautions.)
Certain type 3 serotonin (5-HT3) receptor antagonists used as antiemetic agents (e.g., dolasetron, ondansetron, palonosetron) are associated with QT-interval prolongation.34 If a 5-HT3 receptor antagonist is clinically necessary, granisetron, which has not been associated with QT-interval prolongation, is recommended by some clinicians.34
Pharmacokinetic interaction has not been observed with concomitant use of eribulin and carboplatin.7, 9, 10
Pharmacokinetic interaction unlikely.1, 7, 10 Concomitant administration of ketoconazole, a potent CYP3A4 and P-glycoprotein inhibitor, did not substantially affect AUC values of eribulin in patients with advanced solid tumors in an open-label crossover study.1, 7, 10
Increased severity and duration of oral mucositis has been observed in patients receiving palifermin within 24 hours of myelotoxic chemotherapy administration, presumably because of increased sensitivity of the rapidly dividing epithelial cells to chemotherapy after palifermin treatment.28 Because eribulin can be myelotoxic,1 palifermin should not be administered during or within 24 hours before or after eribulin administration.28
Eribulin mesylate is a nontaxane microtubule dynamics inhibitor antineoplastic agent.1, 2, 4, 5, 6, 7, 10, 12, 13, 17, 23 The drug is a synthetic analog of halichondrin B, which is a naturally occurring product originally isolated from the marine sponge Halichondria okadai and has been shown to possess potent antitumor activity.1, 4, 7, 13, 20, 21, 22, 23 Eribulin appears to have a distinct mechanism of action from that of other currently available antimicrotubule agents (e.g., epothilones, taxanes, vinca alkaloids).2, 4, 5, 6, 7, 10, 13, 21, 22 Similar to these agents, eribulin binds to a unique site on tubulin and blocks cell cycle progression at the G2/M phase, resulting in irreversible mitotic arrest and apoptosis.1, 5, 7, 10, 20 However, unlike these agents, eribulin inhibits the growth of microtubules without affecting the shortening phase and also causes sequestration of tubulin into nonfunctional aggregates.1, 2, 4, 7, 10, 21, 22 In preclinical studies, eribulin demonstrated antitumor activity in paclitaxel-resistant cell lines.6, 7, 10, 13
Eribulin exhibits linear, dose-proportional pharmacokinetics.1, 3, 4, 10, 13, 26, 36 Eribulin exposure after multiple dosing is similar to that following a single dose of the drug; no accumulation of eribulin has been observed with weekly administration.1 Plasma concentrations of the drug decline in a triphasic manner with an initial rapid distribution phase followed by a slower elimination phase with a mean terminal elimination half-life of approximately 40 hours.1, 3, 4, 7, 10, 13, 26, 36 Eribulin is principally excreted in feces; following IV administration, approximately 82% of the dose is eliminated in feces and 9% in urine, mainly as unchanged drug.1 About 49-65% of the drug is bound to plasma proteins.1 Eribulin is primarily metabolized by cytochrome P-450 (CYP) isoenzyme 3A4; however, no major human metabolites of the drug have been detected.1, 10, 13 In vitro studies using human liver microsomes indicate that eribulin does not substantially inhibit CYP isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4 nor induce CYP1 isoenzymes A2, 2C9, 2C19, and 3A4.1, 11 Eribulin is a substrate and weak inhibitor of P-glycoprotein.1, 10, 13
Importance of instructing patients to carefully read the manufacturer's patient information before initiating eribulin therapy and also before receiving each injection of the drug.1
Risk of myelosuppression; importance of patients immediately informing a clinician if they develop any symptoms of an infection (e.g., fever of 100.5°F or higher, chills, cough, burning or pain upon urination).1 Necessity of obtaining complete blood cell counts (CBCs) periodically.1
Risk of peripheral neuropathy.1 Importance of patients informing a clinician if they develop any numbness, tingling, or burning in their hands or feet.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses (e.g., liver and kidney disease, heart problems including congenital long QT syndrome).1
Necessity of advising women to use an effective method of contraception and to avoid breast-feeding while receiving eribulin therapy.1 Advise pregnant women of potential risk to the fetus.1 Importance of women informing a clinician immediately if they are or plan to become pregnant or plan to breast-feed.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Additional Information
Overview® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
1. Eisai Inc. Halaven® (eribulin mesylate) injection prescribing information. Woodcliff Lake, NJ: 2010 Nov.
2. Cortes J, O'Shaughnessy J, Loesch D et al. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet . 2011; 377:914-23. [PubMed 21376385]
3. US Food and Drug Administration. Center for Drug Evaluation and Research: Application number 201532: Summary review for eribulin mesylate. From FDA website. [Web]
4. Cigler T, Vahdat LT. Eribulin mesylate for the treatment of breast cancer. Expert Opin Pharmacother . 2010; 11:1587-93. [PubMed 20450446]
5. Morris PG. Advances in therapy: eribulin improves survival for metastatic breast cancer. Anticancer Drugs . 2010; 21:885-9. [PubMed 20838209]
6. Twelves C, Cortes J, Vahdat LT et al. Phase III trials of eribulin mesylate (E7389) in extensively pretreated patients with locally recurrent or metastatic breast cancer. Clin Breast Cancer . 2010; 10:160-3. [PubMed 20299316]
7. Cortes J, Montero AJ, Glück S. Eribulin mesylate, a novel microtubule inhibitor in the treatment of breast cancer. Cancer Treat Rev . 2011; :[epub ahead of print].
8. Witteveen P, Marchetti S, Roelvink-Mergui M et al. Eribulin mesylate pharmacokinetics in patients with hepatic impairment. J Clin Oncol. 2010; 28 (Suppl. 15): Abstr. No. 2582.
9. Swami U, Petrylak P, Raftopoulos H et al. Phase IB study of eribulin mesylate in combination with carboplatin in patients with advanced solid tumors. J Clin Oncol. 2010; 28 (Suppl. 15): Abstr. No. 2589.
10. Swami U, Chaudhary I, Ghalib MH et al. Eribulin-a review of preclinical and clinical studies. Crit Rev Oncol Hematol . 2011; :[epub ahead of print]. [PubMedCentral][PubMed 21493087]
11. Zhang ZY, King BM, Pelletier RD et al. Delineation of the interactions between the chemotherapeutic agent eribulin mesylate (E7389) and human CYP3A4. Cancer Chemother Pharmacol . 2008; 62:707-16. [PubMed 18431572]
12. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology: breast cancer. Version 2.2011. From NCCN website [Web]
13. Mani S, Swami U. Eribulin mesilate, a halichondrin B analogue, in the treatment of breast cancer. Drugs Today (Barc) . 2010; 46:641-53. [PubMed 20967296]
14. Murphy CG, Seidman AD. Evolving approaches to metastatic breast cancer previously treated with anthracyclines and taxanes. Clin Breast Cancer . 2009; 9 (Suppl. 2):S58-65. [PubMed 19596644]
15. Moreno-Aspitia A, Perez EA. Treatment options for breast cancer resistant to anthracycline and taxane. Mayo Clin Proc . 2009; 84:533-45. [PubMedCentral][PubMed 19483170]
16. Gradishar WJ. The place for eribulin in the treatment of metastatic breast cancer. Curr Oncol Rep . 2011; 13:11-6. [PubMed 21104168]
17. Cortes J, Lorca R. Eribulin mesylate: a promising new antineoplastic agent for locally advanced or metastatic breast cancer. Future Oncol . 2011; 7:355-64. [PubMed 21375468]
18. Cortes J, Vahdat L, Blum JL et al. Phase II study of the halichondrin B analog eribulin mesylate in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline, a taxane, and capecitabine. J Clin Oncol . 2010; 28:3922-8. [PubMed 20679609]
19. Vahdat LT, Pruitt B, Fabian CJ et al. Phase II study of eribulin mesylate, a halichondrin B analog, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol . 2009; 27:2954-61. [PubMed 19349550]
20. Kuznetsov G, Towle MJ, Cheng H et al. Induction of morphological and biochemical apoptosis following prolonged mitotic blockage by halichondrin B macrocyclic ketone analog E7389. Cancer Res . 2004; 64:5760-6. [PubMed 15313917]
21. Smith JA, Wilson L, Azarenko O et al. Eribulin binds at microtubule ends to a single site on tubulin to suppress dynamic instability. Biochemistry . 2010; 49:1331-7. [PubMedCentral][PubMed 20030375]
22. Jordan MA, Kamath K, Manna T et al. The primary antimitotic mechanism of action of the synthetic halichondrin E7389 is suppression of microtubule growth. Mol Cancer Ther . 2005; 4:1086-95. [PubMed 16020666]
23. Anon. Eribulin mesylate (Halaven) for breast cancer. Med Lett Drugs Ther . 2011; 53:30-1. [PubMed 21502935]
24. Institute for Safe Medication Practices. ISMP's list of high-alert medications. Horsham, PA; 2008. From ISMP website ([Web]). Accessed 2011 Jun 10.
25. Eisai Inc. Woodcliff Lake, NJ: Personal communication.
26. . Goel S, Mita AC, Mita M. A phase I study of eribulin mesylate, a mechanicistically novel inhibioty or microtubule dynamics, in patients with advanced solid malignancies. Clin Cancer Res . 2009; 15:4207-12. [PubMed 19509177]
27. Edwards MS, Solimando DA, Waddell JA. Cancer chemotherapy update: eribulin mesylate and denosumab. Hosp Pharm . 2011; 46:247-50.
28. Amgen Inc. Kepivance® (palifermin) for injection, for intravenous use prescribing information. Thousand Oaks, CA; 2009 Apr.
29. Lundbeck Inc. Xenazine® (tetrabenazine) tablets prescribing information. Deerfield, IL.; 2009 Sep.
30. Ortho-McNeil-Janssen Pharmaceuticals. Invega® (paliperidone) extended-release tablets prescribing information. Titusville, NJ; 2009 Jul.
31. Stöllberger C, Huber JO, Finsterer J. Antipsychotic drugs and QT prolongation. Int Clin Psychopharmacol . 2005; 20:243-51. [PubMed 16096514]
32. Schering Corporation, a subsidiary of Merck & Co., Inc. Saphris® (asenapine maleate) sublingual tablets prescribing information. Whitehouse Station, NJ; 2011 Jan.
33. Eisai Ltd. Halaven 0.44 mg/ml solution for injection summary of product characteristics. Hertfordshire, UK; 2011 Mar 25.
34. Piekarz RL, Frye AR, Wright JJ et al. Cardiac studies in patients treated with depsipeptide, FK228, in a phase II trial for T-cell lymphoma. Clin Cancer Res . 2006; 12:3762-73. [PubMed 16778104]
35. Fornier MN. Approved agents for metastatic breast cancer. Semin Oncol . 2011; 38 (Suppl 2):S3-10. [PubMed 21600382]
36. Tan AR, Rubin EH, Walton DC et al. Phase I study of eribulin mesylate administered once every 21 days in patients with advanced solid tumors. Clin Cancer Res . 2009; 15:4213-9. [PubMed 19509146]