Eribulin mesilate, a halichondrin B analogue, in the treatment of breast cancer.
Eisai is developing eribulin mesilate (E-7389), a synthetic macrocyclic ketone analogue of the tubulin inhibitor halichondrin B, for the treatment of a variety of solid tumors that include but are not limited to breast and lung cancer. In this context, eribulin is in phase III clinical trials in breast cancer; however, it has also progressed to phase II for nonsmall cell lung cancer, soft tissue sarcomas, pancreatic, prostate, head and neck cancer, bladder and ovarian and related gynecological tumors. Eribulin has shown synergistic in vitro antiproliferative activity in combination with the breast cancer drugs gemcitabine, epirubicin, trastuzumab, docetaxel and vinorelbine. Clinical trials have established efficacy, safety and a distinct survival advantage of 2.5 months with eribulin as compared to other treatments of physician's choice in metastatic breast cancer patients with heavy pretreatment and taxane resistance. It has a manageable side effect profile, consisting mostly of neutropenia and fatigue, with distinct tolerance at full doses in renal dysfunction, a lower incidence of peripheral neuropathy, minimal chances of drug-drug interactions and hypersensitivity. It appears to be a suitable candidate for third-line monotherapy and beyond for locally advanced and metastatic breast cancer. This review will focus on published and peer-reviewed data on breast cancer.
Albert Einstein College of Medicine, Bronx, New York 10461, USA. smani@montefiore.org
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D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D004988:Ethers, Cyclic / Q000494:pharmacology; D005260:Female; D005663:Furans / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007659:Ketones / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D018942:Macrolides; D008698:Mesylates / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000095662:Polyether Polyketides
D000970:Antineoplastic Agents; D004988:Ethers, Cyclic; D005663:Furans; D007659:Ketones; D018942:Macrolides; D008698:Mesylates; C070519:halichondrin B; D000095662:Polyether Polyketides; C490954:eribulin