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A phase II study of oral enzastaurin in patients with metastatic breast cancer previously treated with an anthracycline and a taxane containing regimen

  • PHASE II STUDIES
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Summary

Purpose: Enzastaurin is a potent, serine-threonine kinase inhibitor which selectively targets PKCβ and PI3K/AKT signaling pathways to reduce cell proliferation, induce apoptosis, and inhibit angiogenesis. As PKCβ and PI3K/AKT signaling are both involved in breast cancer pathogenesis, this phase II study evaluated the efficacy and toxicity of enzastaurin in previously treated patients with metastatic breast cancer (MBC). Patients and Methods: Eligible patients had histologically confirmed MBC with measurable disease, and must have received prior anthracycline and taxane chemotherapy, but not more than two prior regimens for MBC. Human epidermal growth factor 2 (HER2)-positive patients must have progressed on prior trastuzumab therapy. Enzastaurin, 1,125-mg loading dose on day 1 followed by 500 mg daily, was administered orally in 28-day cycles. Response was assessed every 2 cycles according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Results: Twenty-one patients enrolled between November 2006 and September 2007. Fourteen (66.7%) patients completed at least two cycles of therapy. No patients developed Grade 3/4 hematologic toxicity. Grade 3 nonhematologic toxicity was rare (<5%) and most commonly attributed to MBC progression. There were no objective responses and no patients with stable disease for ≥6 months. Median progression-free survival was 1.68 months (95%CI: 1.02, 1.74). Conclusions: Enzastaurin monotherapy was well tolerated, but demonstrated no activity in patients with heavily pretreated MBC.

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Acknowledgements

This trial was supported by Eli Lilly and Company, Indianapolis, IN. The authors thank Luna Musib and John Gill for their editorial support.

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Authors and Affiliations

  1. Indiana University Melvin and Bren Simon Cancer Center, 535 Barnhill Drive, Indianapolis, IN, 46202, USA

    Lida Mina, Menggang Yu, Cindy Johnson, LaTrice G. Vaughn, George W. Sledge & Kathy D. Miller

  2. Dana Farber Cancer Institute, 44 Binney Street, Boston, MA, 02115, USA

    Ian Krop

  3. Northern Indiana Cancer Research Consortium, 615 N. Michigan St. Suite 5520, South Bend, IN, 46601, USA

    Robin T. Zon

  4. Massachusetts General Hospital Cancer Center, 55 Fruit Street, Boston, MA, 02114, USA

    Steven J. Isakoff

  5. Helen F. Graham Cancer Center, 4701 Ogletown Stanton Road, Suite 2200, Newark, DE, 19713, USA

    Charles J. Schneider

  6. Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA

    Yanping Wang, Maria Hristova-Kazmierski & Oluwatoyin O. Shonukan

Authors
  1. Lida Mina
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  2. Ian Krop
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  3. Robin T. Zon
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  4. Steven J. Isakoff
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  5. Charles J. Schneider
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  6. Menggang Yu
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  7. Cindy Johnson
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  8. LaTrice G. Vaughn
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  9. Yanping Wang
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  10. Maria Hristova-Kazmierski
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  11. Oluwatoyin O. Shonukan
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  12. George W. Sledge
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  13. Kathy D. Miller
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Corresponding author

Correspondence to Kathy D. Miller.

Additional information

This study was sponsored by Eli Lilly and Company, Indianapolis, Indiana.

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Mina, L., Krop, I., Zon, R.T. et al. A phase II study of oral enzastaurin in patients with metastatic breast cancer previously treated with an anthracycline and a taxane containing regimen. Invest New Drugs 27, 565–570 (2009). https://doi.org/10.1007/s10637-009-9220-1

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  • DOI: https://doi.org/10.1007/s10637-009-9220-1

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