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

Lida Mina, Ian Krop, Robin T. Zon, Steven J. Isakoff, Charles J. Schneider, Menggang Yu, Cindy Johnson, Latrice G. Vaughn, Yanping Wang, Maria Hristova-Kazmierski, Oluwatoyin O. Shonukan, George W. Sledge, Kathy Miller

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Abstract

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.

Original languageEnglish
Pages (from-to)565-570
Number of pages6
JournalInvestigational New Drugs
Volume27
Issue number6
DOIs
StatePublished - Dec 2009

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Anthracyclines
Breast Neoplasms
Phosphatidylinositol 3-Kinases
enzastaurin
taxane
Protein-Serine-Threonine Kinases
Epidermal Growth Factor
Disease-Free Survival
Cell Proliferation
Apoptosis
Drug Therapy
Therapeutics

Keywords

  • Enzastaurin
  • Metastatic breast cancer
  • Phase II

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Oncology

Cite this

A phase II study of oral enzastaurin in patients with metastatic breast cancer previously treated with an anthracycline and a taxane containing regimen. / Mina, Lida; Krop, Ian; Zon, Robin T.; Isakoff, Steven J.; Schneider, Charles J.; Yu, Menggang; Johnson, Cindy; Vaughn, Latrice G.; Wang, Yanping; Hristova-Kazmierski, Maria; Shonukan, Oluwatoyin O.; Sledge, George W.; Miller, Kathy.

In: Investigational New Drugs, Vol. 27, No. 6, 12.2009, p. 565-570.

Research output: Contribution to journalArticle

Mina, L, Krop, I, Zon, RT, Isakoff, SJ, Schneider, CJ, Yu, M, Johnson, C, Vaughn, LG, Wang, Y, Hristova-Kazmierski, M, Shonukan, OO, Sledge, GW & Miller, K 2009, 'A phase II study of oral enzastaurin in patients with metastatic breast cancer previously treated with an anthracycline and a taxane containing regimen', Investigational New Drugs, vol. 27, no. 6, pp. 565-570. https://doi.org/10.1007/s10637-009-9220-1
Mina, Lida ; Krop, Ian ; Zon, Robin T. ; Isakoff, Steven J. ; Schneider, Charles J. ; Yu, Menggang ; Johnson, Cindy ; Vaughn, Latrice G. ; Wang, Yanping ; Hristova-Kazmierski, Maria ; Shonukan, Oluwatoyin O. ; Sledge, George W. ; Miller, Kathy. / A phase II study of oral enzastaurin in patients with metastatic breast cancer previously treated with an anthracycline and a taxane containing regimen. In: Investigational New Drugs. 2009 ; Vol. 27, No. 6. pp. 565-570.
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AU - Isakoff, Steven J.

AU - Schneider, Charles J.

AU - Yu, Menggang

AU - Johnson, Cindy

AU - Vaughn, Latrice G.

AU - Wang, Yanping

AU - Hristova-Kazmierski, Maria

AU - Shonukan, Oluwatoyin O.

AU - Sledge, George W.

AU - Miller, Kathy

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