Broad-spectrum Preclinical Antitumor Activity of Eribulin (Halaven®): Combination with Anticancer Agents of Differing Mechanisms

Anticancer Res. 2018 Jun;38(6):3375-3385. doi: 10.21873/anticanres.12604.

Abstract

Background: Eribulin is used in many countries to treat patients with advanced breast cancer or liposarcoma and exerts in vivo anticancer activity under monotherapy conditions against various human tumor xenograft models. Here, eribulin in combination with mechanistically different anticancer agents was evaluated.

Materials and methods: Eribulin was combined with cytotoxic agents (capecitabine, carboplatin, cisplatin, doxorubicin, gemcitabine) or targeted agents (bevacizumab, BKM-120, E7449, erlotinib, everolimus, lenvatinib, palbociclib) in tumor xenograft models of breast cancer, melanoma, non-small cell lung cancer (NSCLC), and ovarian cancer.

Results: Across nearly all models, eribulin with either cytotoxic or targeted agents demonstrated combination activity, defined as the activity demonstrably greater than that of either agent alone. Combination activity was absent only with doxorubicin (MDA-MB-435 model) and with lenvatinib (NCI-H1975 model), both of which responded to the agents as monotherapy.

Conclusion: Eribulin has combination activity with multiple agents from different mechanistic classes in several human cancer models, including breast, NSCLC, ovarian, and melanoma.

Keywords: E7389; Eribulin; NSC 707389; chemotherapy; preclinical combinations; targeted agents; xenograft tumor models.

MeSH terms

  • A549 Cells
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Drug Synergism
  • Female
  • Furans / administration & dosage
  • Humans
  • Ketones / administration & dosage
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology
  • MCF-7 Cells
  • Melanoma / drug therapy
  • Melanoma / pathology
  • Mice
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / pathology
  • Xenograft Model Antitumor Assays / methods*

Substances

  • Antineoplastic Agents
  • Furans
  • Ketones
  • eribulin